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Table DM diabetes mellitus

VIEWS: 25 PAGES: 40

									                                                                              Supplementary Table 3: Evidence table

Chapter 1: GLUCOSE

  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                    5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                   design           evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the               recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                moderate-       moderate-
                                                                                                                                                           low)            low-very low)

                                                                                                                                                                           (3)
  DOES GLUCOSE NEED TO BE MEASURED IN PLASMA FOR THE DIAGNOSIS OF DIABETES MELLITUS?                                                                                         Priority: 3 (B2, C1)
  1.a    Glucose should be               When glucose is used to            Clarification            American Diabetes Association.       Guideline        Low             High            Direct relationship between
         measured in plasma in an        establish the diagnosis of                                  Standards of medical care in         expert opinion                                   glucose and complications
         accredited laboratory to        diabetes, it should be measured                             diabetes --2010. Diab Care 2010;                                                      of diabetes has been shown
         establish the diagnosis of      in venous plasma                                            33 (Suppl 1):S11-61                                                                   in earlier high quality studies
         diabetes                        A (high)                                                                                                                                          incorporated in ADA and
                                                                                                     World Health Organization,           Guideline        Low                             WHO guidelines. Difficult to
         Level A                                                                                     Definition and Diagnosis of                                                           evaluate quality of evidence
                                                                                                     Diabetes Mellitus and Intermediate                                                    as plasma glucose has been
                                                                                                     Hyperglycermia: Report of a                                                           sole diagnostic criterion for
                                                                                                     WHO/IDF Consultation. Geneva:                                                         diabetes for many years of
                                                                                                     World Health Organization, 2006                                                       clinical practice.
                                                                                                     Engelgau MM, et al. Comparison       cross-           High                            Glucometers are not
                                                                                                     of fasting and 2-hour glucose and    sectional                                        accurate enough to
                                                                                                     HbA1c levels for diagnosing          population-                                      diagnose diabetes. This
                                                                                                     diabetes. Diagnostic criteria and    based sample                                     represents strong
                                                                                                     performance revisited. Diab Care                                                      agreement of experts.
                                                                                                     1997;20(5):785-91.                                                                    WHO recommends „venous
                                                                                                                                                                                           plasma glucose‖ should be
                                                                                                                                                                                           standard, but due to wide-
                                                                                                                                                                                           spread use of capillary
                                                                                                                                                                                           sampling (especially in under-
                                                                                                                                                                                           resourced countries) capillary
                                                                                                                                                                                           samples are accepted as a
                                                                                                                                                                                           pragmatic solution. However,
                                                                                                                                                                                           evidence does NOT support
                                                                                                                                                                                           use of capillary samples.
                                                                                                     McCance DR, e al. Comparison of      Cross            High                            Provides evidence on the
                                                                                                     tests for glycated haemo-globin      sectional and                                    relation between
                                                                                                     and fasting and two hour plasma      longitudinal                                     complications and
                                                                                                     glucose concentrations as            analysis                                         concomitant results of the
                                                                                                     diagnostic methods for diabetes.                                                      three tests.
                                                                                                     BMJ. 1994; 308(6940): 1323-8.                                                         Recommendation upgraded
                                                                                                     Erratum in: BMJ 1994;                                                                 for direct link between
                                                                                                     309(6958):841                                                                         glucose and DM
                                                                                                                                                                                           complications and outcomes.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        1
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it             4. Key references                    5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                      (2)             (2)
         recommendation                  recommendation with its            necessary to              supporting the new                   design           evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the                recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                 moderate-       moderate-
                                                                                                                                                            low)            low-very low)
                                                                                                                                                                            (3)
  DOES GLUCOSE NEED TO BE MEASURED IN PLASMA FOR THE SCREENING OF DIABETES MELLITUS?                                                                                          Priority: 3 (B2, C1)
  1.b    Glucose should be               When glucose is used for           Former                    American Diabetes Association.       Guideline        Low             Moderate        WHO accepts glucometers for
         measured in plasma in an        screening of high-risk             recommendation was        Standards of medical care in         expert opinion                                   screening, for pragmatic
         accredited laboratory for       individuals, it should be          split for clarification   diabetes --2010. Diab Care 2010;                                                      reasons i.e., lack of access to
         screening of high-risk          measured in venous plasma          and re-grading            33 (Suppl 1):S11-61                                                                   an accredited central lab in
         individuals                     B (moderate)                                                                                                                                       underdeveloped countries.
                                                                                                      World Health Organization,           Guideline        Low                             This represents a strong
         Level E                                                                                      Definition and Diagnosis of                                                           consensus view that it is
                                                                                                      Diabetes Mellitus and Intermediate                                                    ―better than doing nothing‖.
                                                                                                      Hyperglycermia: Report of a
                                                                                                      WHO/IDF Consultation. Geneva:
                                                                                                      World Health Organization, 2006.
                                                                                                      Jesudason DR, et al. Macro-          Population-      Moderate -
                                                                                                      vascular risk and diagnostic         based            high
                                                                                                      criteria for type 2 diabetes:        analysis
                                                                                                      implications for the use of FPG
                                                                                                      and HbA1c for cost-effective
                                                                                                      screening. Diab Care 2003;
                                                                                                      26:485-90.
                                                                                                      Knowler WC, et al. Reduction in      RCT              High                            Recommendation
                                                                                                      the incidence of type 2 diabetes                                                      downgraded for indirectness
                                                                                                      with lifestyle intervention or                                                        – outcome was to reduce
                                                                                                      metformin. N Engl J Med 2002;                                                         DM with treatment/lifestyle
                                                                                                      346:393-403.                                                                          changes.
                                                                                                      Tuomilehto J, et al. Prevention of   RCT              High
                                                                                                      type 2 diabetes mellitus by
                                                                                                      changes in lifestyle among
                                                                                                      subjects with impaired glucose
                                                                                                      tolerance. N Engl J Med 2001;
                                                                                                      344:1343-50.
  1.c                                    Plasma glucose should be           Former                                                                                                          Consensus of experts
                                         measured in an accredited          recommendation was
                                         laboratory when used for           split for clarification
                                         diagnosis of or screening for      and re-grading
                                         diabetes
                                         GPP




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                       2
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                      5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                      (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                     design          evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the               recommendation                                         (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                 moderate-       moderate-
                                                                                                                                                            low)            low-very low)
                                                                                                                                                                            (3)
  ARE SCREENING PROGRAMS FOR DIABETES MELLITUS EFFECTIVE?                                                                                                                     Priority: NOT LISTED
  1.d                                    Outcome studies are needed to      New recommendation       Kahn R, et al. Age at initiation and   Cost-           High            Moderate        No evidence so far that
                                         determine the effectiveness of     based on additional      frequency of screening to detect       effectiveness                                   screening has benefit.
                                         screening                          evidence                 type 2 diabetes: a cost-effective-     study                                           Quality of evidence
                                         C (moderate)                                                ness analysis. Lancet                                                                  downgraded for indirectness.
                                                                                                     2010;375:1365-74
                                                                                                     Glumer C, et al. What determines       Cost-           Moderate
                                                                                                     the cost-effectiveness of diabetes     effectiveness
                                                                                                     screening? Diabetologia 2006;          modeling
                                                                                                     49:1536-44.                            study
                                                                                                     Icks A, et al. Cost-effectiveness of   Review and      Moderate -
                                                                                                     type 2 diabetes screening: results     cost-           low
                                                                                                     from recently published studies.       effectiveness
                                                                                                     Gesundheitswesen 2005; 67              analysis
                                                                                                     Suppl 1:S167-71
                                                                                                     Hoerger TJ, et al. Screening for       Cost-           Moderate
                                                                                                     type 2 diabetes mellitus: a cost-      effectiveness
                                                                                                     effectiveness analysis. Ann Intern     analysis by
                                                                                                     Med 2004; 140:689-99.                  Markov model
                                                                                                     Dallo FJ, Weller SC. Effectiveness     Cross-          High
                                                                                                     of diabetes mellitus screening         sectional
                                                                                                     recommendations. Proc Natl Acad        analysis of
                                                                                                     Sci USA 2003; 100:10574-9.             population-
                                                                                                                                            based study
                                                                                                     Jesudason DR, et al. Macro-            Population-     Moderate -
                                                                                                     vascular risk and diagnostic           based           high
                                                                                                     criteria for type 2 diabetes:          analysis
                                                                                                     implications for the use of FPG
                                                                                                     and HbA1c for cost-effective
                                                                                                     screening. Diab Care 2003;
                                                                                                     26:485-90.
                                                                                                     Perry RC, et al. HbA1c                 RCT             High
                                                                                                     measurement improves the
                                                                                                     detection of type 2 diabetes in
                                                                                                     high-risk individuals with
                                                                                                     nondiagnostic levels of fasting
                                                                                                     plasma glucose: the Early
                                                                                                     Diabetes Intervention Program
                                                                                                     (EDIP). Diab Care 2001; 24:465-
                                                                                                     71


(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                     3
  No     1. NACB 2002                       2. NACB 2011 updated/new             3. Why was it       4. Key references                        5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                         (2)             (2)
         recommendation                     recommendation with its              necessary to        supporting the new                       design           evidence        evidence
         and its grade
                      (1)                   grade and quality of                 modify the          recommendation                                            (high-          (high-
                                                     (2)
                                            evidence                             recommendation?                                                               moderate-       moderate-
                                                                                                                                                               low)            low-very low)
                                                                                                                                                                               (3)
  DOES GLUCOSE NEED TO BE MEASURED IN PLASMA FOR THE MONITORING OF DIABETES MELLITUS?                                                                                            Priority: 3 (B2, C1)
  1.e    Routine measurement of             Routine measurement of plasma        No change           American Diabetes Association.           Guideline        Low             Low
         plasma glucose                     glucose concentrations in an                             Standards of medical care in             expert opinion
         concentrations in an               accredited laboratory is not                             diabetes --2010. Diab Care 2010;
         accredited laboratory is not       recommended as the primary                               33 (Suppl 1):S11-61.
         recommended as the primary         means of monitoring or
         means of monitoring or             evaluating therapy in individuals
         evaluating therapy in              with diabetes
         individuals with diabetes.         B (low)
         Level E
                                                                                                                                                                               (3)
  WHAT ARE THE PRE-ANALYTICAL CONSIDERATIONS IN GLUCOSE TESTING?                                                                                                                 Priority: NOT LISTED
  1.f    Blood for fasting plasma           Blood for fasting plasma glucose     Clarification       WHO Definition and Diagnosis of          Guideline        Low             Low             Evidence reveals a diurnal
         glucose analysis should be         analysis should be drawn in the                          Diabetes Mellitus and Intermediate                                                        variation in FPG, with mean
         drawn after the subject has        morning after the individual has                         Hyperglycemia: Report of a                                                                FPG higher in the morning
         fasted overnight (at least 8 h).   fasted overnight (at least 8 h)                          WHO/IDF Consultation. Geneva:                                                             than in the afternoon,
         Level B                            B (low)                                                  World Health Organization, 2006                                                           indicating that many cases
                                                                                                                                                                                               of diabetes would be missed
                                                                                                     Troisi RJ, et al. Diurnal variation in   Retrospective    High                            in patients seen in the
                                                                                                     fasting plasma glucose:                  population-                                      afternoon. No RCT
                                                                                                     implications for diagnosis of            based study                                      compared morning vs
                                                                                                     diabetes in patients examined in                                                          afternoon testing in terms of
                                                                                                     the afternoon. JAMA 2000;                                                                 diagnostic accuracy or
                                                                                                     284:3157-9.                                                                               outcomes. Therefore quality
                                                                                                     American Diabetes Association.           Guideline        Low                             of evidence is downgraded
                                                                                                     Report of the Expert Committee on                                                         for indirectness. However,
                                                                                                     the Diagnosis and Classification of                                                       there is strong consensus of
                                                                                                     Diabetes Mellitus. Diab Care 1997;                                                        experts that a fasting plasma
                                                                                                     20:1183-97.                                                                               specimen drawn in the
                                                                                                                                                                                               morning should be used.
  1.g    Plasma should be separated         To minimize glycolysis, one          Clarification       Gambino R et al. Acidification of        Observational    High            Moderate        A consistent body of good
         from the cells within 60 min;      should place the sample tube                             blood is superior to sodium                                                               evidence that delay in
         if this is not possible, a tube    immediately in an ice–water                              fluoride alone as an inhibitor of                                                         sample processing leads to
         containing a glycolytic            slurry, and the plasma should be                         glycolysis. Clin Chem                                                                     reduction in glucose in
         inhibitor such as sodium           separated from the cells within                          2009;55:1019-21.                                                                          sample, and thus strong
         fluoride should be used for        30 min. If that cannot be                                                                                                                          consensus that this may
         collecting the sample              achieved, a tube containing a                                                                                                                      alter diagnostic accuracy.
                                            rapidly effective glycolysis                                                                                                                       However, no study is
         Level B                            inhibitor, such as citrate buffer,                                                                                                                 available to determine if this
                                            should be used for collecting the                                                                                                                  leads to unfavorable
                                            sample. Tubes with only enolase                                                                                                                    outcomes or increased rate
                                            inhibitors, such as sodium                                                                                                                         of complications. Therefore
                                            fluoride, should not be relied on                                                                                                                  quality of evidence is
                                            to prevent glycolysis                                                                                                                              downgraded for indirectness.
                                            B (moderate)

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                          4
  No     1. NACB 2002                    2. NACB 2011 updated/new             3. Why was it          4. Key references                     5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its              necessary to           supporting the new                    design          evidence        evidence
         and its grade
                      (1)                grade and quality of                 modify the             recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                             recommendation                                                               moderate-       moderate-
                                                                              ?                                                                            low)            low-very low)

                                                                                                     Bruns DE, Knowler WC.                 Editorial       Low                             In vitro decrease of glucose
                                                                                                     Stabilization of glucose in blood                                                     may lead to missed
                                                                                                     samples: Why it matters. Clin                                                         diagnoses of diabetes in the
                                                                                                     Chem [Editorial] 2009;55:850-2.                                                       large proportion of the
                                                                                                                                                                                           population who have
                                                                                                                                                                                           glucose concentrations near
                                                                                                                                                                                           the diagnostic cut points for
                                                                                                                                                                                           diabetes.
                                                                                                     Sacks DB. Carbohydrates. In:          Review (book    Moderate-
                                                                                                     Burtis CA, Ashwood ER, Bruns          chapter)        low
                                                                                                     DE, eds. Tietz Textbook of Clinical
                                                                                                     Chemistry and Molecular
                                                                                                     Diagnostics, 4th ed. St. Louis:
                                                                                                     Elsevier Saunders, 2006:837
                                                                                                     Boyanton BL, Jr., Blick KE.           Observational   High
                                                                                                     Stability studies of twenty-four
                                                                                                     analytes in human plasma and
                                                                                                     serum. Clin Chem 2002; 48:2242-
                                                                                                     7
                                                                                                     Stahl M, et al. Optimization of       Observational   High
                                                                                                     preanalytical conditions and
                                                                                                     analysis of plasma glucose. 1.
                                                                                                     Impact of the new WHO and ADA
                                                                                                     recommendations on diagnosis of
                                                                                                     diabetes mellitus. Scand J Clin
                                                                                                     Lab Invest 2001; 61:169-79
                                                                                                     Chan AY, et al. Effectiveness of      Observational   High
                                                                                                     sodium fluoride as a preservative
                                                                                                     of glucose in blood. Clin Chem
                                                                                                     1989; 35:315-7.
                                                                                                     Ladenson JH. Nonanalytical            Review (book    Moderate-
                                                                                                     sources of variation in clinical      chapter)        low
                                                                                                     chemistry results. In: Sonnenwirth
                                                                                                     A, Jarett L, eds. Clinical
                                                                                                     Laboratory Methods and
                                                                                                     Diagnosis. St. Louis, MO: C.V.
                                                                                                     Mosby Co., 1980:149




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      5
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                     5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                      (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                    design           evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the               recommendation                                         (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                 moderate-       moderate-
                                                                                                                                                            low)            low-very low)
                                                                                                                                                                            (3)
  DO ANALYTICAL GOALS FOR GLUCOSE ANALYSIS NEED TO CHANGE/IMPROVE WITH THE LOWERED CUTOFF FOR IFG?                                                                            Priority: 2 (A1-3, B2)
  1.h                                    On the basis of biological         New recommendation       Ricos C et al. Current databases      Review           Moderate        Low             Quality of evidence is
                                         variation, glucose measurement     for setting analytical   on biological variation: pros, cons                                                    downgraded for indirectness
                                         should have an analytical          performance goals for    and progress. Scand J Clin Lab                                                         to outcomes and for lack of
                                         imprecision 2.9%, a bias          achieving better         Invest. 1999;59:491-500                                                                primary studies linking
                                         2.2%, and a total error 6.9%.    diagnostic accuracy                                                                                             analytical performance to
                                         To avoid misclassification of      around diagnostic        Fraser CG. The necessity of           Expert opinion   Low                             outcomes. However, there is
                                         patients, the goal for glucose     thresholds.              achieving good laboratory                                                              strong expert consensus that
                                         analysis should be to minimize                              performance. Diabet Med 1990;                                                          analytical uncertainty of
                                         total analytical error, and                                 7:490-3.                                                                               glucose measurement could
                                         methods should be without                                                                                                                          result in misclassification of
                                         measurable bias                                                                                                                                    patients. The related
                                         B (low)                                                                                                                                            recommendation therefore
                                                                                                                                                                                            was upgraded to reflect this
                                                                                                                                                                                            potential impact on patient
                                                                                                                                                                                            centered outcomes.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                       6
Chapter 2: GLUCOSE METERS


  No     1. NACB 2002                     2. NACB 2011 updated/new           3. Why was it              4. Key references                    5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                        (2)             (2)
         recommendation                   recommendation with its            necessary to               supporting the new                   design           evidence        evidence
         and its grade
                      (1)                 grade and quality of               modify the                 recommendation                                        (high-          (high-
                                                   (2)
                                          evidence                           recommendation?                                                                  moderate-       moderate-
                                                                                                                                                              low)            low-very low)
                                                                                                                                                                              (3)
  SHALL PORTABLE METERS BE USED IN DIAGNOSIS AND SCREENING OF DIABETES MELLITUS?                                                                                                Priority: 2 (A3-4, B2, C1)
  2.a    There are no published data      There are insufficient published   New evidence               Dungan K, et al. Glucose             Review           Low             Moderate        WHO recommends plasma,
         to support a role for portable   outcome data to support a role     emerged since 2002         measurement: Confounding issues                                                       but accepts capillary whole
         meters in the diagnosis of       for portable meters and skin-      and clarification. Prior   in setting targets for inpatient                                                      blood using glucometer.
         diabetes or for population       prick (finger-stick) blood         recommendation was         management. Diab Care 2007;
                                          samples in diagnosis of diabetes                                                                                                                    WHO accepts meters for
         screening. The imprecision                                          split into two separate    30(2): 403-409.                                                                       screening for practical and
         of the meters, coupled with      or for population screening        recommendations for
                                                                                                        The Diabetes Research in             Observational    High                            financial reasons. This
         the substantial differences      C (moderate)                       clarity and regarding.                                                                                           represents a strong
         among meters, precludes                                                                        Children Network (DirecNet) Study    (Analytical
                                                                                                        Group. Accuracy of newer                                                              consensus view that it is
         their use in the diagnosis of                                                                                                       evaluations)                                     ‖better than doing nothing‖.
         diabetes and limits their                                                                      generation home blood glucose
         usefulness in screening for                                                                    meters in a Diabetes Research in                                                      Glucometers are not
         diabetes                                                                                       Children Network (DirecNet)                                                           accurate enough to
                                                                                                        inpatient exercise study. Diabetes                                                    diagnose diabetes. This
         Level E                                                                                        Technology and Therapeutics                                                           represents strong agreement
                                                                                                        2005; 7(5): 675-680.                                                                  of experts.
                                          The imprecision of the results,                                                                                                                     Quality of evidence
  2.b                                                                                                   Bohme P, et al. Evolution of         Observational    High
                                          coupled with the substantial                                  analytical performance in portable                                                    downgraded for
                                          differences among meters,                                                                          (Analytical                                      inconsistency and
                                                                                                        glucose meters in the last decade.   evaluations)
                                          precludes the use of glucose                                                                                                                        indirectness of evidence.
                                                                                                        Diab Care 2003; 26(4): 1170-
                                          meters from the diagnosis of                                  1175.
                                          diabetes and limits their
                                          usefulness in screening for
                                          diabetes
                                          A (moderate)
                                                                                                                                                                              (3)
  HOW SHOULD PORTABLE METERS BE USED IN MONITORING TYPE 1 DIABETES MELLITUS?                                                                                                    Priority: NOT LISTED
  2.c    SMBG is recommended for all      Self-monitoring of blood glucose   Clarification              American Diabetes Association.       Guideline        Low             High            Intensive glycemic control in
         insulin-treated patients with    (SMBG) is recommended for all                                 Standards of medical care in         expert opinion                                   patients with type 1 diabetes
         diabetes. For type 1 patients,   insulin-treated patients with                                 diabetes--2010. Diab Care                                                             was achieved in the DCCT
         SMBG is recommended three        diabetes                                                      2010;33 (Suppl 1):S11-61                                                              by participants performing
         or more times a day. SMBG        A (high)                                                                                                                                            SMBG at least four times per
         may be desirable in patients                                                                   DCCT Research Group. The effect      RCT              High                            day, hence the ADA
         treated with sulfonylureas or                                                                  of intensive treatment of diabetes                                                    recommendation and a
         other insulin secretagogues                                                                    on the development and                                                                strong consensus for SMBG
         and in all patients not                                                                        progression of long-term                                                              to be performed three or
         achieving goals                                                                                complications in insulin-dependent                                                    more times per day in type 1
                                                                                                        diabetes mellitus. N Engl J Med                                                       diabetes.
         Level B                                                                                        1993;329:977-986.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                            7
  No     1. NACB 2002                    2. NACB 2011 updated/new             3. Why was it          4. Key references                       5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                       (2)             (2)
         recommendation                  recommendation with its              necessary to           supporting the new                      design          evidence        evidence
         and its grade
                      (1)                grade and quality of                 modify the             recommendation                                          (high-          (high-
                                                  (2)
                                         evidence                             recommendation?                                                                moderate-       moderate-
                                                                                                                                                             low)            low-very low)
                                                                                                                                                                             (3)
  SHOULD PORTABLE METERS BE USED IN MONITORING TYPE 2 DM?                                                                                                                      Priority: 2 (A3, A5, B1-2, C1)
  2.d    In patients with type 2         In patients with type 2 diabetes     New evidence           Allemann S, Houriet C, Diem P,          Systematic      High            High            In spite of the number of
         diabetes, SMBG may help         treated with diet and oral agents,   emerged since the      Stettler C. Self-monitoring of blood    Review                                          high quality new studies and
         achieve better control,         SMBG may help achieve better         2002 publication       glucose in non-insulin treated                                                          evidence reviews, there is
         particularly when therapy is    control, particularly when                                  patients with type 2 diabetes: a                                                        insufficient evidence to claim
         initiated or changed.           therapy is initiated or changed.                            systematic review and meta-                                                             improved outcomes for
         However, there are no data      Data are insufficient, however, to                          analysis. Curr Med Res Opin                                                             SMBG in type 2 DM.
         to support this concept. The    claim an associated                                         2009;25:2903-13                                                                         Therefore clear
         role of SMBG in patients        improvement of health                                                                                                                               recommendations for or
         with stable type 2 diabetes     outcomes. The role of SMBG in                               Poolsup N, Suksomboon N,                Systematic      High                            against SMBG in type 2 DM
         controlled by diet alone is     patients with stable type 2                                 Rattanasookchit S. Meta-analysis        Review                                          cannot be made at this
         not known                       diabetes controlled by diet alone                           of the benefits of self-monitoring of                                                   stage.
                                         is not known                                                blood glucose on glycemic control
         Level C                                                                                     in type 2 diabetes patients: an
                                         C (high)
                                                                                                     update. Diabetes Technol Ther.
                                                                                                     2009;11:775-84
                                                                                                     Farmer A, et al. Impact of self         RCT             High
                                                                                                     monitoring of blood glucose in the
                                                                                                     management of patients with non-
                                                                                                     insulin treated diabetes: open
                                                                                                     parallel group randomised trial.
                                                                                                     BMJ 2007;21;335:132
                                                                                                     Martin S, at al. The ROSSO Study        Epidemiolo-     Moderate
                                                                                                     Group. Self-monitoring of blood         gical cohort
                                                                                                     glucose in type 2 diabetes and          study
                                                                                                     long-term outcome: an epidemio-
                                                                                                     logical study. Diabetologia
                                                                                                     2006;49:271–8.
                                                                                                     Karter AJ, et al.Longitudinal study     Observational   High
                                                                                                     of new and prevalent use of self-       study
                                                                                                     monitoring of blood glucose. Diab
                                                                                                     Care 2006;29:1757–63.
                                                                                                     Welschen LMC, et al. Self-              Systematic      High                            Systematic review of 6 RCTs
                                                                                                     monitoring of blood glucose in          review
                                                                                                     patients with type 2 diabetes
                                                                                                     mellitus who are not using insulin.
                                                                                                     Cochrane Database of Systematic
                                                                                                     Reviews 2005;Issue 2. Art. No.:
                                                                                                     CD005060.
                                                                                                     Welschen LMC, et al. Self-moni-
                                                                                                     toring of blood glucose in patients
                                                                                                     with type 2 diabetes who are not
                                                                                                     using insulin: a systematic review.
                                                                                                     Diab Care 2005;28:1510–7.

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        8
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                      5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                       (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                     design           evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                          (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                  moderate-       moderate-
                                                                                                                                                             low)            low-very low)
                                                                                                     Davidson MB. Counter-point: Self-      Expert opinion   Low
                                                                                                     Monitoring of Blood Glucose in
                                                                                                     Type 2 Diabetic Patients not
                                                                                                     Receiving Insulin: A waste of mo-
                                                                                                     ney. Diab Care 2005;28:1531-3.
                                                                                                     Franciosi M, et al., the QuED          Observational    High
                                                                                                     Study Group. Self-monitoring of        study
                                                                                                     blood glucose in non-insulin-
                                                                                                     treated diabetic patients: a
                                                                                                     longitudinal evaluation of its
                                                                                                     impact on metabolic control. Diab
                                                                                                     Med 2005;22:900–6.
                                                                                                     Guerci B, et al., the ASIA Group.      Multi-center,    Moderate
                                                                                                     Self-monitoring of blood glucose       prospective
                                                                                                     significantly improves metabolic       open label,
                                                                                                     control in patients with type 2        randomized
                                                                                                     diabetes mellitus: the Auto-           trial
                                                                                                     Surveillance Intervention Active
                                                                                                     (ASIA) study. Diabetes Metab
                                                                                                     2003; 29:587–94.
                                                                                                     Harris MI. Frequency of blood          Cross-           High                            NHANES study
                                                                                                     glucose monitoring in relation to      sectional
                                                                                                     glycemic control in patients with      study
                                                                                                     type 2 diabetes. Diab Care
                                                                                                     2001;24:979-82.
                                                                                                     Coster S, et al. Self-monitoring in    Meta-analysis    High                            Meta-analysis of 8 RCTs
                                                                                                     Type 2 diabetes mellitus: a meta-
                                                                                                     analysis. Diab Med 2000;17:755-
                                                                                                     761.
                                                                                                     Faas A, et al. The efficacy of self-   Systematic       High                            11 studies reviewed,
                                                                                                     monitoring of blood glucose in         review                                           including 6 RCTs
                                                                                                     NIDDM subjects. Diab Care
                                                                                                     1997;20:1482-1486.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      9
  No     1. NACB 2002                       2. NACB 2011 updated/new             3. Why was it           4. Key references                       5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                           (2)             (2)
         recommendation                     recommendation with its              necessary to            supporting the new                      design          evidence        evidence
         and its grade
                      (1)                   grade and quality of                 modify the              recommendation                                          (high-          (high-
                                                     (2)
                                            evidence                             recommendation?                                                                 moderate-       moderate-
                                                                                                                                                                 low)            low-very low)
                                                                                                                                                                                 (3)
  WHAT ARE THE PRE-ANALYTICAL CONSIDERATIONS FOR GLUCOSE METERS?                                                                                                                   Priority: 2 (A2-3, B1-2, C1)
         Patients should be instructed in   Patients should be instructed in     Clarification and new   Kristensen GB, et al. Standardized      Observational   High            Moderate
  2.e                                       the correct use of glucose
         the correct use of glucose                                              data                    evaluation of nine instruments for
         meters, including quality          meters, including quality control.                           self-monitoring of blood glucose.
         control. Comparison between        Comparison between SMBG                                      Diab Technol and Therap
         SMBG and concurrent                and concurrent laboratory                                    2008;10:467-77.
         laboratory glucose analysis        glucose analysis should be
         should be performed at regular     performed at regular intervals to                            Kristensen GB, et al. Standardized      Observational   High
         intervals to evaluate the          evaluate the performance of the                              evaluation of instruments for self-
         accuracy of patient results.       meters in the patient’s hands                                monitoring of blood glucose by
                                            B (moderate)                                                 patients and a technologist. Clin
         Level B                                                                                         Chem 2004; 50:1068-71.
                                                                                                         Kabadi UM, et al. The effect of         Observational   Moderate
                                                                                                         recurrent practice at home on the
                                                                                                         acceptability of capillary blood
                                                                                                         glucose readings. Accuracy of self
                                                                                                         blood glucose testing. Diab Care
                                                                                                         1994;10:1110-23.
                                                                                                                                                                                 (3)
  WHAT ARE THE ANALYTICAL CONSIDERATIONS FOR GLUCOSE METERS?                                                                                                                       Priority: 2 (A2-3, B1-2, C1)
  2.f    Multiple performance goals         Multiple performance goals for       Clarification and new   Kristensen GB, et al. Standardized      Observational   High            Low             Performance goal targets
         for portable glucose meters        portable glucose meters have         data                    evaluation of nine instruments for                                                      vary widely and are highly
         have been proposed.                been proposed. These targets                                 self-monitoring of blood glucose.                                                       controversial. No evidence is
         These targets vary widely          vary widely and are highly                                   Diab Technol and Therap                                                                 available that the ADA
         and are highly controversial.      controversial. Manufacturers                                 2008;10:467-77.                                                                         targets of less than 5% total
         No published study has             should work to improve the                                                                                                                           error can be achieved in
         achieved the goals                 imprecision of current meters,                               The Diabetes Research in                Observational   Moderate                        practice.
         proposed by the ADA.               with an intermediate goal of                                 Children Network (DirecNet) Study       (Analytical
                                            limiting total error for 95% of                              Group. Accuracy of newer                                                                Downgraded evidence for
         Manufacturers should work                                                                                                               evaluation)                                     inconsistency, indirectness
         to improve the imprecision         samples to 15% at glucose                                   generation home blood glucose
                                                                                                                                                                                                 and lack of consensus of
         of current meters                  concentrations 5.6 mmol/L (100                              meters in a Diabetes Research in
                                                                                                         Children Network (DirecNet)                                                             experts.
                                            mg/dL) and to <0.8 mmol/L (15
         Level E                                                                                         Inpatient Exercise Study. Diab
                                            mg/dL) at glucose
                                            concentrations <5.6 mmol/L (100                              Technol Ther 2005;7:675-83.
                                            mg/dL). Lower total error would
                                            be desirable and may prove                                   Bohme P, et al. Evolution of            Observational   High
                                            necessary in tight glucose-                                  Analytical Performance in Portable
                                            control protocols and for                                    Glucose Meters in the Last Decade
                                            avoiding hypoglycemia in all                                 Diab Care 2003;26:1170-5.
                                            settings                                                     Skeie S, et al. Instruments for self-   Observational   High
                                            C (low)                                                      monitoring of blood glucose:
                                                                                                         comparisons of testing quality
                                                                                                         achieved by patients and a
                                                                                                         technician. Clin Chem
                                                                                                         2002;48:994-1003.

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                              10
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                     5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                    design          evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                     Weitgasser R, et al. Newer            Observational   High
                                                                                                     portable glucose meters -
                                                                                                     analytical improvement compared
                                                                                                     with previous generation devices?
                                                                                                     Clin Chem 1999;45:1821-1825.
                                                                                                     American Diabetes Association.        Guideline       Low
                                                                                                     Self-monitoring of blood glucose.
                                                                                                     Diab Care 1996;19 (S 1):S62-66.
                                                                                                     Novis DA, Jones BA. Interinstitu-     Observational   High                            Q-probe
                                                                                                     tional comparison of bedside blood
                                                                                                     glucose monitoring program
                                                                                                     characteristics, accuracy perfor-
                                                                                                     mance, and quality control
                                                                                                     documentation. Arch Pathol Lab
                                                                                                     Med 1998;122:495-502.
                                                                                                     Barr JT, et al. Ancillary (bedside)   Guideline       Low
                                                                                                     blood glucose testing in acute and
                                                                                                     chronic care facilities. NCCLS
                                                                                                     1994;14:1-14.
  2.g    We recommend meters that        Meters should measure and          No change, rewording                                           Expert          Low             Very low
         measure and report plasma       report plasma glucose                                                                             consensus
         glucose concentrations to       concentrations to facilitate
         facilitate comparison with      comparison with assays
         assays performed in             performed in accredited
         accredited laboratories.        laboratories
         Level E                         GPP




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                    11
  No     1. NACB 2002                    2. NACB 2011 updated/new            3. Why was it            4. Key references                            5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                              (2)             (2)
         recommendation                  recommendation with its             necessary to             supporting the new                           design           evidence        evidence
                      (1)
         and its grade                   grade and quality of                modify the               recommendation                                                (high-          (high-
                                                  (2)
                                         evidence                            recommendation?                                                                        moderate-       moderate-
                                                                                                                                                                    low)            low-very low)
                                                                                                                                                                                    (3)
  ARE GLUCOSE METERS ADEQUATE FOR WIDESPREAD USE IN INTENSIVE CARE UNITS?                                                                                                             Priority: 2 (A1-3, B2, C1)
  2.h    Clinical studies are needed     Studies are needed to determine     Clarification and        Meynaar IA, et al. Accuracy of               Observational    High            Moderate-low
         to determine the analytic       the analytical goals (quality       expansion of scope of    AccuChek glucose measurement                 study
         goals for glucose meters. At    specifications) for glucose         recommendation to        in intensive care patients. Crit
         a minimum, the end points       meters in SMBG and in intensive     intensive care setting   Care Med 2009;37:2691-6.
         should be glycated              care units
         hemoglobin and frequency        C (moderate)
         of hypoglycemic episodes.       Recommendations for future
  2.i    Ideally, outcomes (e.g.,                                                                     Boyd JC, Bruns DE. Monte Carlo               Simulation       Moderate
                                         research: Important end points                               simulation in establishing                   modeling
         long-term complications and     in studies of SMBG should
         hypoglycemia) should also                                                                    analytical quality requirements for
                                         include, at a minimum,                                       clinical laboratory tests meeting
         be examined                     hemoglobin A1c (Hb A1c) and                                  clinical needs. Methods Enzymol
         Level E                         frequency of hypoglycemic                                    2009;467:411-33.
                                         episodes to ascertain whether
                                         improved meters enable patients                              Scott MG, et al. Tight glucose               Expert opinion   Low
                                         to achieve better glucose                                    control in the intensive care unit:
                                         control. For studies of meter use                            Are glucose meters up to the task?
                                         in intensive or critical care,                               Clin Chem 2009; 55:18-20.
                                         important end points include
                                         mean blood glucose, frequency                                Scott MG, et al. Tight glucose               Expert opinion   Low
                                         of hypoglycemia, and variation                               control in critically ill adults [Letter].
                                         of glucose control. Ideally,                                 JAMA 2008; 300(23):2726-7.
                                         outcomes (e.g., long-term
                                                                                                      Wiener RS, et al. Benefits and risks Systematic               Moderate
                                         complications) should also be
                                                                                                      of tight glucose control in critically ill review and
                                         examined
                                                                                                      adults. JAMA 2008;300(8):933-944. meta-analysis
                                         GPP
                                                                                                      Hoedemaekers CW, et al.                      Observational    High
                                                                                                      Accuracy of bedside glucose                  study
                                                                                                      measurement from three gluco-
                                                                                                      meters in critically ill patients. Crit
                                                                                                      Care Med 2008;36(11):3062-6.
                                                                                                      Dungan K, et al. Glucose                     Narrative        Low
                                                                                                      measurement: confounding issues              review
                                                                                                      in setting targets for inpatient
                                                                                                      management. Diabetes Care
                                                                                                      2007;30:403-9.
                                                                                                      Finkielman J, et al: Agreement               Observational    Low
                                                                                                      between bedside blood and plasma             study
                                                                                                      glucose measurement in the ICU
                                                                                                      setting. Chest 2005;127:1749-51.
                                                                                                      van den Berghe G, et al. Intensive           RCT              Moderate
                                                                                                      insulin therapy in the critically ill
                                                                                                      patients. N Engl J Med.
                                                                                                      2001;345(19):1359-1367.


(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                    12
Chapter 3: CONTINUOUS MINIMALLY-INVASIVE GLUCOSE ANALYSES

  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                   5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                  design            evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the               recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                                                                                           (3)
  ARE THERE ADEQUATE WELL CONTROLLED STUDIES DEMONSTRATING THE IMPACT OF CONTINUOUS GLUCOSE                                                                                  Priority: 2 (A1, A3, B2, C1)
  MONITORS ON INTERMEDIATE OUTCOMES (E.G. HbA1c) TO JUSTIFY WIDESPREAD ADOPTION OF THE TECHNOLOGY?
  GIVEN THE HIGH COSTS OF THE TECHNOLOGY, ARE THERE EVIDENCE-BASED SELECTION CRITERIA FOR ITS USE AND                                                                      (3)
                                                                                                                                                                             Priority: 2 (A3, C1)
  POTENTIAL REIMBURSEMENT?
  3.a    Noninvasive glucose analyses    Real-time continuous glucose       Gluco Watch              The Juvenile Diabetes Research      RCT              High             High            Three age subgroups pre-
         cannot be recommended as        monitoring (CGM) in conjunction    technology is no         Foundation Continuous Glucose                                                         specified for outcome
         replacements for SMBG or        with intensive insulin regimens    longer on market and     Monitoring Study Group:                                                               assessment
         glucose measurements by an      can be a useful tool to lower Hb   has been supplanted      N.Engl.J.Med. 2008;359:1464-
         accredited laboratory.          A1c in selected adults (age >25    by subcutaneous          1476
         Ongoing developments in the     years) with type 1 diabetes        CGM devices.
         field, such as use of the       A (high)
         new Gluco Watch Biographer,                                        Additional evidence is
         may influence this                                                 available about
         recommendation.                                                    effectiveness of real-
         Level E                                                            time CGM.
  3.b                                    Although the evidence for          New recommendation       The Juvenile Diabetes Research      RCT              Moderate         Moderate        This was a per-protocol
                                         lowering Hb A1c is not as strong   based on additional      Foundation Continuous Glucose                                                         post-hoc analysis of the
                                         for children, teens, and younger   evidence                 Monitoring Study Group:                                                               relationship between HbA1c
                                         adults, real-time CGM may be                                N.Engl.J.Med. 2008;359:1464-                                                          lowering and days per week
                                         helpful in these groups. Success                            1476                                                                                  of use, not an intention-to-
                                         correlates with adherence to                                                                                                                      treat analysis or the primary
                                         ongoing use of the device                                                                                                                         outcome. Therefore the
                                         B (moderate)                                                                                                                                      quality of evidence and the
                                                                                                                                                                                           strength of recommendation
                                                                                                                                                                                           were downgraded.


  3.c                                    Real-time CGM may be a             New recommendation       Garg S, et al. Improvement in       RCT              Moderate         Low             Comparison of real-time vs.
                                         supplemental tool to SMBG in       based on additional      glycemic excursions with a                                                            blinded CGM (outcomes
                                         individuals with hypoglycemia      evidence                 transcutaneous, real-time                                                             were patients’ time in hyper-
                                         unawareness and/or frequent                                 continuous glucose sensor - a                                                         glycemic and hypoglycemic
                                         episodes of hypoglycemia                                    randomized controlled trial. Diab                                                     ranges). Evidence is indirect
                                         B (low)                                                     Care 2006;29:44-50                                                                    as the outcome was a
                                                                                                                                                                                           surrogate biochemical
                                                                                                                                                                                           marker (although patient-
                                                                                                                                                                                           related), i.e. not clinical
                                                                                                                                                                                           episodes of hypoglycemia.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      13
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                   5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                  design            evidence        evidence
         and its grade
                      (1)                grade and quality of               modify the               recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                                                                                           (3)
  ARE CONTINUOUS GLUCOSE MONITORS SUFFICIENTLY ACCURATE FOR CLINICAL USE BY PATIENTS?                                                                                        Priority: 1 (A1-4, B1-2, C1)
  3.d                                    Patients require extensive         New recommendation                                           Clinical          Low             Very low        FDA labeling of the device
                                         training in using the device.                                                                   experience                                        (for trend assessment, not
                                         Available devices must be                                                                       and FDA                                           treatment decisions - use
                                         calibrated with SMBG readings,                                                                  labeling of the                                   SMBG for insulin dosing)
                                         and the latter are recommended                                                                  device
                                         for making treatment changes
                                         GPP




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                       14
Chapter 4: NONINVASIVE GLUCOSE ANALYSIS


  No     1. NACB 2002                    2. NACB 2011 updated/new            3. Why was it           4. Key references                      5. Study       6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its             necessary to            supporting the new                     design         evidence        evidence
         and its grade
                      (1)                grade and quality of                modify the              recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                            recommendation?                                                               moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                                                                                           (3)
  SHOULD PRESENT NON-INVASIVE GLUCOSE SENSING TECHNOLOGY BE RECOMMENDED FOR MONITORING GLYCEMIA?                                                                             Priority: 3 (A3, A5, B2)
  4.a    Noninvasive glucose analyses    No noninvasive sensing              New recommendation      Arnold MA, et al. Selectivity          Animal model   Low             Very low        Demonstration of selectivity
         cannot be recommended as        technology is currently approved    and clarification       assessment of noninvasive                                                             issues. Downgraded for
         replacements for SMBG or        for clinical glucose                                        glucose measurements based on                                                         indirectness
         glucose measurements by an      measurements of any kind.                                   analysis of multivariate calibration
         accredited laboratory.          Major technological hurdles                                 vectors. J Diabetes Sci Technol
         Ongoing developments in the     must be overcome before                                     2007;1:454-62.
         field, such as use of the new   noninvasive sensing technology
         Gluco Watch Biographer may      will be sufficiently reliable to                            Tura A, et al. Non-invasive            Review of      Low                             Review with assessment of
         influence this                  replace existing portable meters,                           glucose monitoring: assessment of      technologies                                   feasibility of each approach
         recommendation.                 implantable biosensors, or                                  technologies and devices
                                         minimally invasive technologies                             according to quantitative criteria.
         Level E                                                                                     Diabetes Res Clin Pract
                                         C (very low)                                                2007;77:16-40.
                                                                                                     Arnold MA, Small GW.                   Review of      Low                             Review with listing of critical
                                                                                                     Noninvasive glucose sensing. Anal      technologies                                   analytical parameters
                                                                                                     Chem 2005;77:4529-39.
                                                                                                     Khalil OS. Non-invasive glucose        Review of      Low                             Review with assessment of
                                                                                                     measurements at the dawn of the        technologies                                   feasibility of each approach
                                                                                                     new millennium: An update.
                                                                                                     Diabetes Technol Ther
                                                                                                     2004;6:660-697.
                                                                                                     Gutman S, et al. Regulatory            Consensus      Low                             Listing of anticipant FDA
                                                                                                     aspects of noninvasive glucose         statement                                      requirements for approval of
                                                                                                     measurements. Diabetes Technol                                                        any future non-invasive
                                                                                                     Ther 2002;4:779-81.                                                                   sensing technology.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                         15
Chapter 5: GESTATIONAL DIABETES MELLITUS (GDM)

  No     1. NACB 2002                    2. NACB 2011 updated/new            3. Why was it           4. Key references                     5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its             necessary to            supporting the new                    design          evidence        evidence
         and its grade
                      (1)                grade and quality of                modify the              recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                            recommendation?                                                               moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                                                                                           (3)
  WHAT ARE THE STRATEGIES FOR DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS?                                                                                      Priority: 1 (A5, B2)
  5.a                                    All pregnant women not              New recommendation      American Diabetes Association.        Guideline,      High            High            Based on the HAPO study
                                         previously known to have            based on additional     Standards of medical care in          position                                        and the IADPS criteria, ADA
                                         diabetes should undergo testing     evidence of             diabetes --2011. Diab Care            statement                                       recommends that women
                                         for gestational diabetes mellitus   associations of         2011;34 (Suppl 1):S11-61                                                              with risk factors for type 2
                                         (GDM) at 24–28 weeks of             maternal glycemia and                                                                                         diabetes are screened for
                                         gestation                           perinatal outcome and                                                                                         diabetes at the first prenatal
                                         A (high)                            RCT results showing                                                                                           visit.
                                                                             benefit from treating
                                                                             mild GDM and expert     International Association of          Guideline,      High                            Expert Consensus Panel
                                                                             consensus.              Diabetes and Pregnancy Study          expert                                          appointed by IADPSG
                                                                                                     Groups. International association     consensus                                       recommended ―outcome
                                                                                                     of diabetes and pregnancy study                                                       based‖ criteria for the
                                                                                                     groups recommendations on the                                                         classification of glucose
                                                                                                     diagnosis and classification of                                                       concentrations in pregnancy.
                                                                                                     hyperglycemia in pregnancy. Diab
                                                                                                     Care 2010;33:676-82.
                                                                                                     Hyperglycemia and Adverse             Prospective     High
                                                                                                     Pregnancy Outcome (HAPO)              observational
                                                                                                     Study Cooperative Research            study of a
                                                                                                     Group: Hyperglycemia and              multicenter
                                                                                                     Adverse Pregnancy Outcome             cohort
                                                                                                     (HAPO) Study: Associations with
                                                                                                     neonatal anthropometrics.
                                                                                                     Diabetes 2009;58:453-459.
                                                                                                     Landon MB, et al. A multicenter,      RCT             High                            This RCT does not deal with
                                                                                                     randomized trial of treatment for                                                     the diagnosis of GDM
                                                                                                     mild gestational diabetes. N Engl J                                                   directly but provides
                                                                                                     Med 2009;361:1339                                                                     evidence that treating mild
                                                                                                                                                                                           GDM improves outcome.
                                                                                                     Hyperglycemia and Adverse             Prospective     High                            Strong evidence for
                                                                                                     Pregnancy Outcome (HAPO)              observational                                   continuous association
                                                                                                     Study Cooperative Research            study of                                        between maternal glucose
                                                                                                     Group (Metzger BE, HAPO Study         multicenter                                     levels and pregnancy
                                                                                                     PI). Hyperglycemia and Adverse        cohort                                          outcome
                                                                                                     Pregnancy Outcomes. N Engl J
                                                                                                     Med 2008;358:1991-2002
                                                                                                     Crowther CA, et al. Effect of         RCT             High                            This RCT does not deal with
                                                                                                     treatment of gestational diabetes                                                     the diagnosis of GDM
                                                                                                     mellitus on pregnancy outcomes.                                                       directly but provides
                                                                                                     N Engl J Med 2005;352:2477                                                            evidence that treating mild
                                                                                                                                                                                           GDM improves outcome.

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                       16
  No       1. NACB 2002                       2. NACB 2011 updated/new            3. Why was it              4. Key references                      5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                                (2)             (2)
           recommendation                     recommendation with its             necessary to               supporting the new                     design            evidence        evidence
                        (1)
           and its grade                      grade and quality of                modify the                 recommendation                                           (high-          (high-
                                                       (2)
                                              evidence                            recommendation?                                                                     moderate-       moderate-
                                                                                                                                                                      low)            low-very low)
  5.b                                         GDM should be diagnosed by a        New recommendation         International Association of           Guideline,        High            Moderate*       This guideline was based on
                                              75-g OGTT according to the          based on additional        Diabetes and Pregnancy Study           expert                                            the HAPO study and on the
                                              IADPSG criteria derived from the    evidence and expert        Groups. International association      consensus                                         opinions of the IADPSG
                                              HAPO study                          consensus.                 of diabetes and pregnancy study                                                          Consensus Panel members
                                              A (moderate)                                                   groups recommendations on the                                                            because associations
                                                                                                             diagnosis and classification of                                                          between maternal glycemia
                                                                                                             hyperglycemia in pregnancy. Diab                                                         and clinical outcomes were
                                                                                                             Care 2010;33:676-82.                                                                     continuous with no obvious
                                                                                                                                                                                                      thresholds at which risks
                                                                                                                                                                                                      increased. Therefore a
                                                                                                                                                                                                      consensus was required to
                                                                                                                                                                                                      translate these results into
                                                                                                                                                                                                      clinical practice.
                                                                                                             Hyperglycemia and Adverse              Prospective       High                            The study of 25,000
                                                                                                             Pregnancy Outcome (HAPO)               multi-national                                    participants revealed strong,
                                                                                                             Study: associations with neonatal      epidemiologic                                     graded, predominantly linear
                                                                                                             anthropometrics. Diabetes              study                                             and continuous associations
                                                                                                             2009;58:453                                                                              between maternal glycemia
                                                                                                                                                                                                      and primary study outcomes
                                                                                                             Metzger, et al. Summary and            Conference        Moderate-                       Opinion of world-wide
                                                                                                             Recommendations of the Fifth           review            low                             experts based on findings of
                                                                                                             International Workshop-                                                                  the HAPO outcome study.
                                                                                                             Conference on Gestational
                                                                                                             Diabetes Mellitus. Diab Care
                                                                                                             2007;30:S251-S260.


      * NB: The HAPO study and the subsequent guideline published suggest setting diagnostic thresholds at OR 1.75, but OR 1.5 and 2.0 were also considered.
      The authors themselves suggest the followings:
      It is likely that additional well-designed randomized controlled trials and other clinical studies will be needed to determine
      1) cost-effective therapeutic strategies for treatment of GDM diagnosed by the IADPSG Consensus Panel–recommended criteria;
      2) optimal glycemic treatment targets;
      3) appropriate follow-up of mothers to determine risks for later development of diabetes, other metabolic disorders, or CVD risk factors; and
      4) follow-up of children to assess potential associations of maternal glycemia with long-term risks of obesity, altered glucose metabolism, and CVD risk factors.

      Therefore recommendations are likely to change as more evidence becomes available or modified locally for resource considerations. Therefore the quality of evidence is downgraded to moderate but, due to strong
      consensus on the current criteria, the strength of recommendation is A.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                                 17
      Chapter 6: URINARY GLUCOSE

  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                   5. Study         6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                  design           evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                       (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                               moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                                                                                          (3)
  IS THERE A ROLE FOR URINE GLUCOSE TESTING IN THE MANAGEMENT OF DIABETES MELLITUS?                                                                                         Priority: NOT LISTED
  6.a    Semi-quantitative urine         Semiquantitative urine glucose     No change                Goldstein DE, et al. Tests of       Guideline        Low             Low              Downgraded for low quality
         glucose testing is not          testing is not recommended for                              glycemia in diabetes. Diab Care                                                       and indirectness of
         recommended for routine         routine care of patients with                               2004;27:1761-73.                                                                      evidence. However,
         care of patients with           diabetes mellitus                                                                                                                                 consensus is strong against
         diabetes mellitus                                                                           American Diabetes Association.      Guideline        Low                              the use of this test. IDF
                                         B (low)                                                     Tests of glycemia in diabetes.
         Level C                                                                                                                                                                           supports urine glucose
                                                                                                     Diab Care 1999;22:S77-9.                                                              monitoring where blood
                                                                                                                                                                                           glucose is not available or
                                                                                                                                                                                           affordable.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                    18
      Chapter 7: KETONE TESTING

  No     1. NACB 2002                     2. NACB 2011 updated/new            3. Why was it          4. Key references                       5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                        (2)             (2)
         recommendation                   recommendation with its             necessary to           supporting the new                      design           evidence        evidence
                      (1)
         and its grade                    grade and quality of                modify the             recommendation                                           (high-          (high-
                                                   (2)
                                          evidence                            recommendation?                                                                 moderate-       moderate-
                                                                                                                                                              low)            low-very low)
                                                                                                                                                                              (3)
  WHICH PATIENTS SHOULD BE ADVISED TO MEASURE URINE OR BLOOD KETONES AT HOME, AND UNDER WHAT                                                                                    Priority: 2 (A2-4)
  CIRCUMSTANCES?
  7.a    Ketones should be measured       Ketones measured in urine or        No change              ADA: Standards of Medical Care          Guideline        Low             Very low        Expert opinion, clinical
         in urine or blood by patients    blood in the home setting by                               in Diabetes—2009; Diab Care             expert opinion                                   experience
         with diabetes in the home        patients with diabetes and in the                          2009; 32 (Suppl 1):S13-S61
         setting and in the               clinic/hospital setting should be
         clinic/hospital setting as an    considered only an adjunct to                              ADA: Hyperglycemic crises in            Guideline        Low
         adjunct to the diagnosis of      the diagnosis of diabetic                                  diabetes (position statement). Diab     expert opinion
         diabetic ketoacidosis            ketoacidosis (DKA)                                         Care 2004; 27 (Suppl 1):S94-102
         Level E                          GPP

  7.b    Urine ketone determinations      Urine ketone measurements           No change              ADA Tests of glycemia position          Guideline        Low             Very low        Based on lack of
         should not be used to            should not be used to diagnose                             statement, DiaB Care 2001; 23           expert opinion                                   measurement of beta-
         diagnose or monitor the          or monitor the course of DKA                               (Suppl 1):S80-82).                                                                       hydroxybutyrate by
         course of DKA                    GPP                                                                                                                                                 nitroprusside
         Level A
                                                                                                                                                                              (3)
  ARE DIRECT MEASUREMENTS OF HBA PREFERABLE TO NITROPRUSSIDE MEASUREMENTS OF KETONES?                                                                                          Priority: 3 (A2)
  7.c   Blood ketone determinations       Blood ketone determinations         No change              Wiggam MI, et al. Treatment of          RCT              Moderate        Moderate        Outcome not clinically
        that rely on the nitroprusside    that rely on the nitroprusside                             diabetic ketoacidosis using                                                              meaningful
        reaction should be used only      reaction should be used only as                            normalization of blood 3-
                                          an adjunct to diagnose DKA and                                                                                                                      Downgraded for indirectness
        as an adjunct to diagnose                                                                    hydroxybutyrate concentration as                                                         of evidence
        DKA and should not be used        should not be used to monitor                              the end point of emergency
        to monitor treatment of DKA.      DKA treatment. Specific                                    management. A randomized
        Specific measurement of           measurement of -hydroxybutiric                            controlled study. Diabetes Care
        HBA in blood can be used for     acid in blood can be used for                              1997;20:1347-52.
        diagnosis and monitoring of       diagnosis and monitoring of DKA
        DKA. Further studies are          B (moderate)                                               Umpierrez GE, et al. Clinical utility   Observational    Moderate                        Comparison of two
        needed to determine if the test                                                              of beta-hydroxybutyrate                 cohort study                                     strategies of monitoring DKA
        offers any clinical advantage                                                                determined by reflectance meter in
        over more traditional                                                                        the management of diabetic
        management approaches                                                                        ketoacidosis. Diab Care
        (e.g., measurements of serum                                                                 1995;18:137-8.
        CO2, anion gap, or pH).                                                                      Noyes KJ, et al. Hydroxybutyrate        Observational    Moderate                        Comparison of two
        Level E                                                                                      near-patient testing to evaluate a      cohort study                                     strategies of monitoring DKA
                                                                                                     new endpoint for intravenous
                                                                                                     insulin therapy in the treatment of
                                                                                                     diabetic ketoacidosis in children.
                                                                                                     Pediatr Diabetes 2007;8:150-156




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        19
Chapter 8: HEMOGLOBIN A1c

  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                     5. Study       6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                    design         evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                       (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                               moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                                                                                          (3)
  HOW GLYCATED HEMOGLOBIN SHOULD BE USED IN MONITORING DIABETES MELLITUS?                                                                                                   Priority: NOT LISTED
  8.a    Glycated hemoglobin (GHb)       Hb A1c should be measured          Clarification            American Diabetes Association.        Guideline      Moderate        Moderate         The DCCT and UKPDS had
         should be measured routinely    routinely in all patients with                              Standards of medical care in                                                          determined the relationship
         in all patients with diabetes   diabetes mellitus to document                               diabetes--2010. Diab Care                                                             between the results of a
         mellitus to document their      their degree of glycemic control                            2011;34 (Suppl 1):S11-61.                                                             specific GHb test (HbA1c)
         degree of glycemic control.     A (moderate)                                                                                                                                      and long-term complications
                                                                                                     Nathan DM, et al. Management of       Consensus      Low                              in patients with type 1 and
         Level A                                                                                     hyperglycaemia in type 2 diabetes:    statement                                       type 2 diabetes, respectively
                                                                                                     a consensus algorithm for the
                                                                                                     initiation and adjustment of                                                          HbA1c has become a
                                                                                                     therapy. A consensus statement                                                        surrogate outcome measure
                                                                                                     from the American Diabetes                                                            in DM but this represents
                                                                                                     Association and the European                                                          indirect evidence and
                                                                                                     Association for the Study of                                                          therefore of moderate
                                                                                                     Diabetes. Diabetologia                                                                quality. However there is
                                                                                                     2006;49:1711-21.                                                                      strong consensus for
                                                                                                                                                                                           measuring HbA1c routinely in
                                                                                                     U.K. Prospective Diabetes Study       RCT            High                             DM monitoring. Therefore
                                                                                                     (UKPDS) Group. Intensive blood-                                                       the recommendation is
                                                                                                     glucose control with sulphonyl-                                                       upgraded.
                                                                                                     ureas or insulin compared with
                                                                                                     conventional treatment and risk of
                                                                                                     complications in patients with type
                                                                                                     2 diabetes (UKPDS 33). UK
                                                                                                     Prospective Diabetes Study
                                                                                                     (UKPDS) Group. Lancet
                                                                                                     1998;352:837-53
                                                                                                     DCCT. The effect of intensive         RCT            High
                                                                                                     treatment of diabetes on the
                                                                                                     development and progression of
                                                                                                     long-term complications in insulin-
                                                                                                     dependent diabetes mellitus. N
                                                                                                     Engl J Med 1993;329:977-86.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      20
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                   5. Study         6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                  design           evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                       (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                               moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                                                                                          (3)
  WHAT ARE THE ANALYTICAL CONSIDERATIONS AND GOALS FOR HbA1c MEASUREMENT?                                                                                                   Priority: 2 (A1)
  8.b    Laboratories should use         Laboratories should use only Hb    Clarification and        Hanas R, John G. 2010               Consensus        Moderate        Low              Differences in HbA1c reported
         only GHb assay methods          A1c assay methods that are         addition of new          consensus statement on the          statement                                         led to an agreement among
         that are certified by the       certified by the National          recommendation           worldwide standardization of the                                                      IFCC and the major diabetes
         National Glycohemoglobin        Glycohemoglobin                    based on expert          hemoglobin A1c measurement.                                                           organizations to report HbA1c
         Standardization Program as      Standardization Program            consensus                Clin Chem 2010;56:1362-4                                                              results as the IFCC result and
         traceable to the DCCT           (NGSP) as traceable to the                                                                                                                        as the equivalent NGSP
         reference. In addition,         DCCT reference. The                                         Weykamp C, et al. The IFCC          Progress         Moderate                         DCCT-aligned result. Some,
         laboratories that measure       manufacturers of Hb A1c assays                              reference measurement system        report                                            but not all, organizations
         GHb should participate in a     should also show traceability to                            for HbA1c: a 6-year progress                                                          have agreed to report HbA1c
         proficiency-testing program,    the IFCC reference method                                   report. Clin Chem 2008;54:240-8                                                       as the DCCT-aligned
         such as the CAP                 GPP                                                         Goldstein DE, et al. Tests of       Positions        Low                              percentage and the IFCC
         Glycohemoglobin Survey,                                                                     glycemia in diabetes. Diab Care     statement                                         value.
         that uses fresh blood                                                                       2004;27:1761-73                                                                       Impact on patient outcomes
         samples with targets set by                                                                                                                                                       is unknown and indirect,
         the National                                                                                Hoelzel W, et al. IFCC reference    Method-          High                             therefore quality of evidence
         Glycohemoglobin                                                                             system for measurement of           comparison                                        is downgraded. However,
         Standardization Program                                                                     hemoglobin A1c in human blood       study                                             there is strong consensus of
         Laboratory Network                                                                          and the national standardization                                                      experts on HbA1c reporting.
         Level B                                                                                     schemes in the United States,
                                                                                                     Japan, and Sweden: a method-
                                                                                                     comparison study. Clin Chem
                                                                                                     2004;50:166-74.
  8.c                                    Laboratories that measure Hb                                Jeppsson JO, et al. Approved        Method           High
                                         A1c should participate in a                                 IFCC reference method for the       development
                                         proficiency-testing program,                                measurement of HbA1c in human
                                         such as the College of American                             blood. Clin Chem Lab Med
                                         Pathologists (CAP) Hb A1c                                   2002;40:78-89.
                                         survey, that uses fresh blood
                                         samples with targets set by the                             Little RR, et al. The national      Analytical       Moderate                         Retrospective analysis of
                                         NGSP Laboratory Network                                     glycohemoglobin standardization     study                                             analytical performance of the
                                         GPP                                                         program: a five-year progress re-                                                     NGSP network and clinical
                                                                                                     port. Clin Chem 2001;47:1985-92.                                                      labs in HbA1c measurement
                                                                                                     Little RR, Goldstein DE.            Analytical       Low
                                                                                                     Standardization of                  study
                                                                                                     glycohemoglobin measurements.
                                                                                                     AACC Endo 1995;13:109-24




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      21
  No     1. NACB 2002                        2. NACB 2011 updated/new               3. Why was it            4. Key references                     5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                             (2)             (2)
         recommendation                      recommendation with its                necessary to             supporting the new                    design          evidence        evidence
                      (1)
         and its grade                       grade and quality of                   modify the               recommendation                                        (high-          (high-
                                                      (2)
                                             evidence                               recommendation?                                                                moderate-       moderate-
                                                                                                                                                                   low)            low-very low)
  8.d    Laboratories should be aware        Laboratories should be aware of        Clarification and new    Ziemer DC, et al. Glucose-            Cross-          Moderate        Low             Quality of evidence
         of potential interferences,         potential interferences, including     recommendation           independent, black-white              sectional                                       downgraded for indirectness
         including hemoglobinopathies        hemoglobinopathies,that may            based on experience      differences in hemoglobin A1c         study
         that may affect GHb test            affect Hb A1c test results,            and published reports.   levels: a cross-sectional analysis
         results. In selecting assay         depending on the method used.                                   of 2 studies. Ann Intern Med
         methods, laboratories should        In selecting assay methods,                                     2010;152:770-7
         consider the potential for          laboratories should consider the
                                             potential for interferences in their                            Selvin E, et al. Glycated             Observational   High
         interferences in their particular                                                                   hemoglobin, diabetes, and
                                             particular patient population. In                                                                     cohort study
         patient population                                                                                  cardiovascular risk in nondiabetic
                                             addition, disorders that affect
         Level A                             erythrocyte turnover may cause                                  adults. N Engl J Med
                                             spurious results, regardless of                                 2010;362:800-11
                                             the method used                                                 Bry L, et al. Effects of hemoglobin   Review          Low
                                             GPP                                                             variants and chemically modified
                                                                                                             derivatives on assays for
                                                                                                             glycohemoglobin [Review]. Clin
                                                                                                             Chem 2001;47:153-63.
                                                                                                             Schnedl WJ, et al. Evaluation of      Test            Moderate
                                                                                                             HbA1c determination methods in        comparison
                                                                                                             patients with hemoglobinopathies.     study
                                                                                                             Diab Care 2000;23:339-44.
                                                                                                             Roberts WL, et al. Glycohemo-         Test            Moderate
                                                                                                             globin results in samples with        comparison
                                                                                                             hemoglobin C or S trait: a            study
                                                                                                             comparison of four test systems.
                                                                                                             Clin Chem 1999;45:906-9
                                                                                                             Weykamp CW, et al. Influence of       Multi/center    Moderate
                                                                                                             hemoglobin variants and               method
                                                                                                             derivatives on glycohemoglobin        comparison
                                                                                                             determinations, as investigated by    study
                                                                                                             102 laboratories using 16
                                                                                                             methods. Clin Chem
                                                                                                             1993;39:1717-23.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                            22
  No     1. NACB 2002                      2. NACB 2011 updated/new           3. Why was it          4. Key references                     5. Study       6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                    recommendation with its            necessary to           supporting the new                    design         evidence        evidence
                      (1)
         and its grade                     grade and quality of               modify the             recommendation                                       (high-          (high-
                                                    (2)
                                           evidence                           recommendation?                                                             moderate-       moderate-
                                                                                                                                                          low)            low-very low)
  8.e    Laboratories should use GHb       Desirable specifications for Hb    Clarification and      Little RR, et al. Status of HbA1c     Review         Moderate        Low              This study used the
         assay methods with an             A1c measurement are an             rewording of           measurement and goals for                                                             reference change value
         interassay CV<5% (ideally         intralaboratory CV <2% and an      recommendations        improvement: From chaos to order                                                      (also called critical
         <3%). At least two control        interlaboratory CV <3.5%. At                              for improving diabetes care. Clin                                                     difference) to calculate an
         materials with different mean     least 2 control materials with                            Chem 2011;in press                                                                    appropriate analytical goal
         values should be analyzed as      different mean values should be
         an independent measure of         analyzed as an independent                                Sacks DB. CAP Surveys:                National       Moderate                         The body of evidence is of
         assay performance.                measure of assay performance                              Participant Summary for               survey                                          low quality for indirectness of
         Laboratories should verify        B (low)                                                   Glycohemoglobin Survey 2010 Set       (<10% from                                      the data to clinical
         specimens below the lower                                                                   GH2-A. Northfield, IL: College of     outside US)                                     outcomes, but there is
         limit of the reference interval                                                             American Pathologists, 2010.                                                          strong consensus of experts
         or greater than 15% by repeat     Samples with Hb A1c results                                                                                                                     for appropriate analytical
  8.f    testing. If Schiff base (labile                                                             Goodall I, et al. Desirable           Consensus      Low                              specifications to avoid
                                           below the lower limit of the                              performance standards for             statement
         pre-HbA1c) interferes with the    reference interval or >15% Hb                                                                                                                   unfavorable outcomes of
         assay method, it should be                                                                  HbA(1c) analysis - precision,                                                         misclassifications and
                                           A1c should be verified by repeat                          accuracy and standardisation:
         removed prior to assay            testing                                                                                                                                         mismanagement of patients.
                                                                                                     consensus statement of the
         Level C                           B (low)                                                   Australasian Association of                                                           Therefore the
                                                                                                     Clinical Biochemists (AACB), the                                                      recommendation was
                                                                                                     Australian Diabetes Society                                                           upgraded.
                                                                                                     (ADS), the Royal College of
                                                                                                     Pathologists of Australasia
                                                                                                     (RCPA), Endocrine Society of
                                                                                                     Australia (ESA), and the Australian
                                                                                                     Diabetes Educators Association
                                                                                                     (ADEA). Clin Chem Lab Med
                                                                                                     2007;45:1083-97.
  8.g                                      Hb A1c values that are                                    Bry L, et al. Effects of hemoglobin   Review         Low
                                           inconsistent with the clinical                            variants and chemically modified
                                           presentation should be                                    derivatives on assays for
                                           investigated further                                      glycohemoglobin [Review]. Clin
                                           GPP                                                       Chem 2001;47:153-63
                                                                                                     Marshall SM, Barth JH.                Consensus      Low
                                                                                                     Standardization of HbA1c              statement
                                                                                                     measurements: a consensus
                                                                                                     statement. Ann Clin Biochem
                                                                                                     2000;37:45-6




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        23
  No     1. NACB 2002                      2. NACB 2011 updated/new            3. Why was it         4. Key references                     5. Study       6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                    recommendation with its             necessary to          supporting the new                    design         evidence        evidence
                      (1)
         and its grade                     grade and quality of                modify the            recommendation                                       (high-          (high-
                                                    (2)
                                           evidence                            recommendation?                                                            moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                                                                                          (3)
  WHAT ARE THE HbA1c TREATMENT GOALS IN DIABETES MELLITUS?                                                                                                                  Priority: 2 (A1, A2)
  8.h    Treatment goals should be based Treatment goals should be             Clarification         ADA. Standards of medical care in     Guideline      Moderate        High             Converging validity of
         on ADA recommendations which based on American Diabetes                                     diabetes--2010. Diab Care                                                             several controlled clinical
         include maintaining GHb          Association recommendations,                               2010;33 (Suppl 1):S11-61.                                                             trials on patient-centered
         concentrations <7% and           which include generally                                                                                                                          outcomes in type 1 and type
         reevaluation of the treatment    maintaining Hb A1c                                         Duckworth W, et al. Glucose           RCT            High                             2 diabetes. Upgraded for
         regimen for GHb values > 8%.     concentrations at <7% and                                  control and vascular complications                                                    directness and consistency
         (Note that these values are      more-stringent goals in selected                           in veterans with type 2 diabetes. N                                                   and strong consensus of
         applicable only if the assay     individual patients if they can be                         Engl J Med 2009;360:129-39                                                            experts and several clinical
         method is certified as traceable achieved without significant                               Gerstein HC, et al. Effects of        RCT            High                             organizations.
         to the DCCT reference.)          hypoglycemia or other adverse
                                          treatment effects. Somewhat                                intensive glucose lowering in type
         Level B                          higher intervals are                                       2 diabetes. N Engl J Med
                                          recommended for children and                               2008;358:2545-59
                                          adolescents and may be
                                                                                                     Patel A, et al. Intensive blood       RCT            High
                                          appropriate for patients with a
                                                                                                     glucose control and vascular
                                          limited life expectancy, extensive
                                                                                                     outcomes in patients with type 2
                                          comorbid illnesses, a history of
                                                                                                     diabetes. N Engl J Med
                                          severe hypoglycemia, or
                                                                                                     2008;358:2560-72.
                                          advanced complications (note
                                          that these values are applicable                           Berg AH, Sacks DB. Haemoglobin        Review         Low
                                          only if the NGSP has certified                             A1c analysis in the management
                                          the assay method as traceable                              of patients with diabetes: from
                                          to the DCCT reference)                                     chaos to harmony. J Clin Pathol
                                           A (high)                                                  2008;61:983-7.
                                                                                                     Qaseem A, et al. Glycemic control     Guideline,     Moderate
                                                                                                     and type 2 diabetes mellitus: the     consensus
                                                                                                     optimal hemoglobin A1c targets. A     statement
                                                                                                     guidance statement from the
                                                                                                     American College of Physicians.
                                                                                                     Ann Intern Med 2007;147:417-22
                                                                                                     ADA. Implications of the Diabetes     Position       Low
                                                                                                     Control and Complications Trial       statement
                                                                                                     (position statement). Diab Care
                                                                                                     2000;23 (Suppl 1):S24-6
                                                                                                     DCCT. The relationship of             RCT            High
                                                                                                     glycemic exposure (HbA1c) to the
                                                                                                     risk of development and
                                                                                                     progression of retinopathy in the
                                                                                                     diabetes control and complications
                                                                                                     trial. Diabetes 1995;44:968-83




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                     24
  No     1. NACB 2002                        2. NACB 2011 updated/new           3. Why was it          4. Key references                    5. Study      6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                      recommendation with its            necessary to           supporting the new                   design        evidence        evidence
                      (1)
         and its grade                       grade and quality of               modify the             recommendation                                     (high-          (high-
                                                      (2)
                                             evidence                           recommendation?                                                           moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                                                                                          (3)
  WHAT SHOULD BE THE FREQUENCY OF HbA1c MONITORING IN DIABETES MELLITUS?                                                                                                    Priority: NOT LISTED
  8.i    GHb testing should be               Hb A1c testing should be           No change              ADA. Standards of medical care in    Guideline     Moderate        Low              240 patients; followed x1
         performed at least biannually       performed at least biannually in                          diabetes--2010. Diab Care                                                           year; 50% had HbA1c
         in all patients and quarterly for   all patients and quarterly for                            2010;33 Suppl 1:S11-61.                                                             measured every 3 months;
         patients whose therapy has          patients whose therapy has                                                                                                                    50% no HbA1c measured.
         changed or are not meeting          changed or who are not meeting                                                                                                                Does not directly evaluate
         treatment goals                     treatment goals                                                                                                                               frequency – only testing vs
         Level B                             B (low)                                                                                                                                       no testing. Moreover, the
                                                                                                       Larsen ML, Horder M, Mogensen        RCT           Moderate                         best correlations of HbA1c
                                                                                                       EF. Effect of long-term monitoring                                                  with complications have
                                                                                                       of glycosylated hemoglobin levels                                                   been based on quarterly
                                                                                                       in insulin-dependent diabetes                                                       HbA1c testing for capturing
                                                                                                       mellitus. N Engl J Med                                                              overall glycemic exposure.
                                                                                                       1990;323:1021-5                                                                     However, there is no
                                                                                                                                                                                           consensus on the optimal
                                                                                                                                                                                           frequency of HbA1c testing.
                                                                                                                                                                                           Most recommendations are
                                                                                                                                                                                           based on strong expert
                                                                                                                                                                                           consensus.
                                                                                                                                                                          (3)
  SHOULD HbA1c BE USED FOR SCREENING AND DIAGNOSIS OF DIABETES MELLITUS?                                                                                                    Priority: 1 (A1-5, B2, C1)
  8.j                                        Hb A1c may be used for the         New recommendation     ADA. Standards of medical care in    Guideline     Moderate        Moderate         The data supporting the use
                                             diagnosis of diabetes, with        based on additional    diabetes--2010. Diab Care                                                           of HbA1c, i.e. its relationship
                                             values 6.5% being diagnostic.     evidence and           2010;33 (Suppl 1):S11-61.                                                           with risk of retinopathy, is
                                             An NGSP-certified method           consensus of experts                                                                                       similar to the data that
                                             should be performed in an                                 American Association of Clinical     Guideline     Moderate                         support glucose testing as
                                             accredited laboratory.                                    Endocrinologists/American                                                           the means of diagnosis.
                                             Analogous to its use in the                               College of Endocrinology                                                            These are definitional
                                             management of diabetes, factors                           statement on the use of                                                             issues. Both the ADA and
                                             that interfere with or adversely                          hemoglobin A1c for the diagnosis                                                    the American Endocrinology
                                             affect the Hb A1c assay will                              of diabetes. Endocr Pract                                                           societies endorsed the
                                             preclude its use in diagnosis                             2010;16:155-6                                                                       HbA1c test for diagnosis.
                                             A (moderate)                                              Cheng YJ, et al. Association of      Population-   High                             Other international
                                                                                                       A1C and fasting plasma glucose       based cross                                    organizations, including the
                                                                                                       levels with diabetic retinopathy     sectional                                      WHO and IDF, are
                                                                                                       prevalence in the U.S. population:                                                  considering HbA1c for
                                                                                                       Implications for diabetes                                                           diabetes diagnosis and
                                                                                                       diagnostic thresholds. Diab Care                                                    screening, therefore there is
                                                                                                       2009;32(11): 2027-32                                                                an emerging strong
                                                                                                                                                                                           consensus on the topic,
                                                                                                                                                                                           which resulted in upgrading
                                                                                                                                                                                           the recommendation.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        25
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                    5. Study        6. Level of     7. Quality of    8. Comments
                                                                                                                                                                    (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                   design          evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                       (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                               moderate-       moderate-
                                                                                                                                                          low)            low-very low)
                                                                                                     Nathan DM et al. for the             Expert          Low                              A HbA1c value of 6.5% or
                                                                                                     International Expert Committee on    consensus                                        greater was considered
                                                                                                     the Diagnosis of Diabetes. Report                                                     diagnostic based on the
                                                                                                     on the Role of the Glycated                                                           observed relationship with
                                                                                                     Hemoglobin (A1C) Assay in the                                                         retinopathy in more than
                                                                                                     Diagnosis of Diabetes. Diab Care                                                      28,000 persons. This
                                                                                                     2009;32:1327-34                                                                       represents direct relationship
                                                                                                                                                                                           to outcomes and thus quality
                                                                                                     Sabanayagam C, et al.                Population-     High                             of evidence is upgraded.
                                                                                                     Relationship between glycated        based cross
                                                                                                     haemoglobin and microvascular        sectional
                                                                                                     complications: is there a natural
                                                                                                     cut-off point for the diagnosis of
                                                                                                     diabetes? Diabetologia
                                                                                                     2009;52(7):1279-89.
                                                                                                     Ito C, et al. Importance of OGTT     Population-     High
                                                                                                     for diagnosing diabetes mellitus     based cross
                                                                                                     based on prevalence and              sectional
                                                                                                     incidence of retinopathy. Diab Res
                                                                                                     Clin Pract. 2000;49(2-3): 181-6

  8.k                                    Point-of-care Hb A1c assays are    New recommendation       American Diabetes Association.       Guideline       Moderate        Moderate         The ADA cautions that
                                         not sufficiently accurate to use                            Standards of medical care in                                                          POCT devices for HbA1c
                                         for the diagnosis of diabetes                               diabetes --2011. Diab Care                                                            should not be used for
                                         B (moderate)                                                2011;34 (Suppl 1):S11-61                                                              diagnosis.
                                                                                                     Lenters-Westra E, Slingerland RJ.    Analytical      Moderate
                                                                                                     Six of eight hemoglobin A1c point-   study
                                                                                                     of-care instruments do not meet
                                                                                                     the general accepted analytical
                                                                                                     performance criteria. Clin Chem
                                                                                                     2010;56:44-52




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                      26
Chapter 9: GENETIC MARKERS

  No     1. NACB 2002                        2. NACB 2011 updated/new            3. Why was it            4. Key references                       5. Study           6. Level of     7. Quality of   8. Comments
                                                                                                                                                                               (2)             (2)
         recommendation                      recommendation with its             necessary to             supporting the new                      design             evidence        evidence
                      (1)
         and its grade                       grade and quality of                modify the               recommendation                                             (high-          (high-
                                                      (2)
                                             evidence                            recommendation?                                                                     moderate-       moderate-
                                                                                                                                                                     low)            low-very low)
                                                                                                                                                                                     (3)
  IS THERE A ROLE FOR GENETIC TESTING IN TYPE 1 DIABETES MELLITUS?                                                                                                                     Priority: NOT LISTED
  9.a    Routine measurement of              Routine measurement of genetic      New information is       Concannon P, et al. Genetics of         Review             Moderate        Moderate        Useful review of genetic
         genetic markers is not of value     markers is not of value at this     available on mutations   type 1A diabetes. N Engl J Med                                                             factors outside the HLA
         at this time for the diagnosis or   time for the diagnosis or           in the proinsulin and    2009;360:1646                                                                              region.
         management of patients with         management of patients with         other genes that are
         type 1 diabetes. For selected       type 1 diabetes. For selected       linked to neonatal       Murphy R, et al. Clinical               Linkage            High                            Monogenic diabetes below
         diabetic syndromes, valuable        diabetic syndromes, including       diabetes                 implications of a molecular genetic     analyses                                           the age of six needs to be
         information can be obtained         neonatal diabetes, valuable                                  classification of monogenic beta-                                                          considered for monogenic
         with definition of diabetes-        information can be obtained with                             cell diabetes. Nat Clin Pract                                                              diabetes
         associated mutations                definition of diabetes-associated                            Endocrinol Metab 2008;4:200-13.
                                             mutations
         Level E                                                                                          Edghill EL, et al. Insulin mutation     Linkage            High                            Many mutations than known
                                             A (moderate)                                                 screening in 1,044 patients with        analyses in                                        hitherto affect the human
                                                                                                          diabetes: mutations in the INS          multiple                                           preproinsulin gene
                                                                                                          gene are a common cause of              familes
                                                                                                          neonatal diabetes but a rare cause
                                                                                                          of diabetes diagnosed in childhood
                                                                                                          or adulthood. Diabetes
                                                                                                          2008;57:1034
                                                                                                          Støy J, et al. Neonatal Diabetes        Linkage            Moderate                        Diabetes below the age of
                                                                                                          International Collaborative Group.      analyses                                           six months needs to be
                                                                                                          Insulin gene mutations as a cause                                                          considered for monogenic
                                                                                                          of permanent neonatal diabetes.                                                            diabetes.
                                                                                                          Proc Natl Acad Sci USA.
                                                                                                          2007;104(38):15040-4


                                                                                                          Hagopian WA, et al. TEDDY-- The         Observational      High                            In contrast to other studies,
                                                                                                          Environ-mental Determinants of          study                                              the TEDDY study has
                                                                                                          Diabetes in the Young: an                                                                  sufficient statistical power to
                                                                                                          observational clinical trial. Ann N Y                                                      answer questions related to
                                                                                                          Acad Sci 2006;1079:320-6.                                                                  environmental triggers for
                                                                                                                                                                                                     islet autoimmunity and type
                                                                                                                                                                                                     1 diabetes.
                                                                                                          Barker JM, et al. Clinical              Screening          Moderate                        Early diagnosis may prevent
                                                                                                          characteristics of children             study of                                           hospitalization with
                                                                                                          diagnosed with type 1 diabetes          children at risk                                   ketoacidosis and preserve
                                                                                                          through intensive screening and         for type 1                                         residual beta cells. More
                                                                                                          follow-up. Diab Care                    diabetes                                           outcome studies are needed
                                                                                                          2004;27:1399-404.                                                                          to prove this.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                                  27
  No     1. NACB 2002                       2. NACB 2011 updated/new           3. Why was it         4. Key references                      5. Study           6. Level of     7. Quality of   8. Comments
                                                                                                                                                                         (2)             (2)
         recommendation                     recommendation with its            necessary to          supporting the new                     design             evidence        evidence
                      (1)
         and its grade                      grade and quality of               modify the            recommendation                                            (high-          (high-
                                                     (2)
                                            evidence                           recommendation?                                                                 moderate-       moderate-
                                                                                                                                                               low)            low-very low)
                                                                                                     Graham J, et al. Genetic effects on    Population-        Moderate                        First time INS VNTR were
                                                                                                     age-dependent onset and islet cell     based case-                                        found to be associated with
                                                                                                     auto- antibody markers in type 1       control study                                      INS VNTR.
                                                                                                     diabetes. Diabetes 2002;51:1346-
                                                                                                     55
                                                                                                     Fajans SS, et al. Molecular            Review             Low                             Careful analysis of family
                                                                                                     mechanisms and clinical                                                                   history of diabetes is
                                                                                                     pathophysiology of maturity-onset                                                         important to the detection of
                                                                                                     diabetes of the young. N Engl J                                                           monogenic diabetes.
                                                                                                     Med 2001;345:971-80
                                                                                                     Kukreja A, Maclaren NK. Auto-          Review             Moderate
                                                                                                     immunity and diabetes. J Clin
                                                                                                     Endocrinol Metab 1999;84:4371
                                                                                                     Rewers M, et al. Newborn scree-        Screening          Moderate                        It is possible to screen
                                                                                                     ning for HLA markers associated        study of                                           newborn children to identify
                                                                                                     with IDDM: diabetes autoimmunity       children at risk                                   those at increased risk for
                                                                                                     study in the young (DAISY).            for type 1                                         developing type 1 diabetes.
                                                                                                     Diabetologia 1996;39:807               diabetes                                           This strategy cannot be
                                                                                                                                                                                               recommended until there is
                                                                                                     Ziegler AG, et al. Prophylactic        Review             Moderate                        a proven intervention
                                                                                                     insulin treatment in relatives at                                                         available to delay or prevent
                                                                                                     high risk for type 1 diabetes.                                                            the disease.
                                                                                                     Diabetes Metab Rev 1993;9:289
                                                                                                                                                                               (3)
  IS THERE A ROLE FOR GENETIC TESTING IN TYPE 2 DIABETES MELLITUS?                                                                                                               Priority: NOT LISTED
  9.b    There is no role for routine       There is no role for routine       No change             Meigs JB, et al. Genotype score in     Genome wide        Moderate        Moderate        Risk alleles in these loci all
         genetic testing in patients with   genetic testing in patients with                         addition to common risk factors for    association                                        have relatively small effects
         type 2 diabetes. These studies     type 2 diabetes. These studies                           prediction of type 2 diabetes. N       case-control                                       (odds ratios 1.1 to 1.3) and
         should be confined to the          should be confined to the                                Engl J Med 2008;359:2208-19.           study                                              do not significantly enhance
         research setting and               research setting and evaluation                                                                                                                    our ability to predict risk of
         evaluation of specific             of specific syndromes                                    Scott LJ, et al. A genome- wide        Genome wide        Moderate                        type 2 diabetes
         syndromes                                                                                   association study of type 2            association
                                            A (moderate)                                             diabetes in Finns detects multiple     case-control
         Level E                                                                                     susceptibility variants. Science       study
                                                                                                     2007;316:1341
                                                                                                     Saxena R, et al. Genome wide           Genome wide        Moderate
                                                                                                     association analysis identifies loci   association
                                                                                                     for type 2 diabetes and triglyceride   case-control
                                                                                                     levels. Science 2007;316: 1331         study




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                            28
Chapter 10: AUTOIMMUNE MARKERS

  No     1. NACB 2002                    2. NACB 2011 updated/new            3. Why was it             4. Key references                     5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                         (2)             (2)
         recommendation                  recommendation with its             necessary to              supporting the new                    design            evidence        evidence
                      (1)
         and its grade                   grade and quality of                modify the                recommendation                                          (high-          (high-
                                                  (2)
                                         evidence                            recommendation?                                                                   moderate-       moderate-
                                                                                                                                                               low)            low-very low)
                                                                                                                                                                               (3)
  SHOULD GAD65, IA-2 OR INSULIN AUTOANTIBODIES BE USED FOR THE DIAGNOSIS, SCREENING, MONITORING OF TYPE 1                                                                        Priority: 1.5 (A1-5, C1)
                                                                                                                                                                               (3)
  AND TYPE 2 DIABETES?                                                                                                                                                           Priority: 3 (A3-4, C1)
  10.a   Islet cell autoantibodies are   Islet cell autoantibodies are       Considerable progress     Bingley PJ,et al. Measurement of      Analytical test   Moderate        Low             International workshops
         recommended for screening       recommended for screening           has been made to          islet cell antibodies in the Type 1   evaluation                                        using serum exchange
         of non-diabetic family          nondiabetic family members who      standardize islet cell    Diabetes Genetics Consortium:                                                           exercises provide measures
         members who wish to             wish to donate part of their        autoantibody tests.       efforts to harmonize procedures                                                         of inter-laboratory variation.
         donate part of their            pancreas for transplantation into                             among the laboratories.                                                                 Quality of evidence is
         pancreas for transplantation    a relative with end-stage type 1                              Clin Trials. 2010;7(1 Suppl):S56-                                                       downgraded for indirectness.
         to a relative with end stage,   diabetes                                                      64.
         immune-mediated (type 1)        B (low)
         diabetes. Islet cell
  10.b                                   Islet cell autoantibodies are not                             Törn C, et al. Participating          Analytical test   Moderate
         autoantibodies are not
                                         recommended for routine                                       Laboratories. Diabetes Antibody       evaluation
         recommended for routine
                                         diagnosis of diabetes, but                                    Standardization Program:
         diagnosis of diabetes nor for
                                         standardized islet cell                                       evaluation of assays for
         screening
                                         autoantibody tests may be used                                autoantibodies to glutamic acid
         Level E                         for classification of diabetes in                             decarboxylase and islet antigen-2.
                                         adults and in prospective studies                             Diabetologia. 2008;51(5):846-52.
                                         of children at genetic risk for
                                         type 1 diabetes after HLA typing
                                         at birth
                                         B (low)
  10.c   Screening from GAD65            Screening patients with type 2      Considerable progress     Rolandsson O, Palmer JP. Latent       Review            Low             Low             Review suggesting that islet
         antibodies in patients          diabetes for islet cell             has been made to          autoimmune diabetes in adults                                                           autoantibody positivity
         diagnosed with type 2           autoantibodies is not               standardize islet         (LADA) is dead: long live                                                               should suffice to classify
         diabetes is not                 recommended at present.             autoantibody tests. It    autoimmune diabetes!                                                                    adult diabetes patients with
         recommended at present to       Standardized islet cell             is not clear to what      Diabetologia. 2010;53(7):1250-3.                                                        ―autoimmune diabetes‖ is
         be reclassified with type 1     autoantibodies are tested in        extent a positive islet                                                                                           GAD65 autoantibody
         diabetes.                       prospective clinical studies of     autoantibody test                                                                                                 positive.
                                         type 2 diabetes patients to         would suffice to alter
         Level E                         identify possible mechanisms of                                                                                                                       Strength of recommendation
                                                                             diagnostic criteria.                                                                                              is upgraded for strong
                                         secondary failures of treatment
                                         of type 2 diabetes                                                                                                                                    consensus
                                         B (low)




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                          29
  No     1. NACB 2002                      2. NACB 2011 updated/new            3. Why was it           4. Key references                       5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                           (2)             (2)
         recommendation                    recommendation with its             necessary to            supporting the new                      design            evidence        evidence
                      (1)
         and its grade                     grade and quality of                modify the              recommendation                                            (high-          (high-
                                                    (2)
                                           evidence                            recommendation?                                                                   moderate-       moderate-
                                                                                                                                                                 low)            low-very low)
  10.d   Screening of relatives of         Screening for islet cell            Clarification and       Patterson CC, et al. Incidence          Multicentre       Moderate        Low             Epidemiology data
         patients with type 1 diabetes     autoantibodies in relatives of      addition of new         trends for childhood type 1             prospective
         or of persons in the general      patients with type 1 diabetes or    recommendation          diabetes in Europe during 1989-         registration
         population for islet cell         in persons from the general         based on new            2003 and predicted new cases            study
         autoantibodies is not             population is not recommended       evidence                2005-20: a multicentre prospective
         recommended at present            at present. Standardized islet                              registration study. Lancet
                                           cell autoantibodies are tested in                           2009;373: 2027-33
         Level E                           prospective clinical studies
                                           B (low)                                                     Maclaren N, et al. Only multiple        Review            Low                             Data only applicable to first
                                                                                                       autoantibodies to islet cells (ICA),                                                      degree relatives who
                                                                                                       insulin, GAD65, IA-2 and IA-2beta                                                         comprise only 10-15% of
                                                                                                       predict immune-mediated (Type 1)                                                          newly diagnosed type 1
                                                                                                       diabetes in relatives. J Autoimmun                                                        diabetes children.
                                                                                                       1999;12:279-87                                                                            Quality of the overall body of
                                                                                                       Verge CF, et al. Prediction of type     Multicentre       Moderate                        evidence was downgraded
                                                                                                       I diabetes in first- degree relatives   prospective                                       for lack of suitably powered
                                                                                                       using a combination of insulin,         registration                                      studies or RCTs
                                                                                                       GAD, and ICA512bdc/IA-2                 study                                             investigating the value of
                                                                                                       autoantibodies. Diabetes                                                                  islet cell autoantibody testing
                                                                                                       1996;45:926-33.                                                                           for screening purposes

  10.e   There is currently no role for    There is currently no role for      No change               Sosenko JM et al. Glucose               Prospective       Moderate        Low             Data on first degree relatives
         measurement of islet cell         measurement of islet cell                                   excursions between states of            family study of                                   suggest an important
         autoantibodies in the             autoantibodies in the monitoring                            glycemia with progression to type       islet                                             contribution of insulin
         monitoring of patients in         of patients in clinical practice.                           1 diabetes in the diabetes              autoantibody                                      sensitivity on glucose
         clinical practice. Islet cell     Islet cell autoantibodies are                               prevention trial-type 1 (DPT-1).        positive                                          tolerance.
         autoantibodies are measured       measured in research protocols                              Diabetes Prevention Trial-Type 1        subjects
                                                                                                       Study Group. Diabetes.                                                                    Quality of the overall body of
         in research protocols and         and in some clinical trials as                                                                                                                        evidence was downgraded
         some clinical trials as           surrogate end points                                        2010;59(10):2386-9.
                                                                                                                                                                                                 for lack of sufficient data
         surrogate endpoints               B (low)                                                                                                                                               from multiple studies
         Level E
  10.f   It is important that              It is important that islet cell     Clarification, but no   Bonifacio E, et al Harmonization of     Analytical test   Moderate        Moderate        Standardization was
          autoantibodies be measured       autoantibodies be measured          change                  glutamic acid decarboxylase and         evaluation                                        possible between three
          only in an accredited            only in an accredited laboratory                            islet antigen-2 autoantibody                                                              expert laboratories.
          laboratory with an established   with an established quality-                                assays for national institute of
          quality control program and      control program and                                         diabetes and digestive and kidney
          participation in a proficiency   participation in a proficiency-                             diseases consortia. J Clin
          testing program                  testing program                                             Endocrinol Metab.
         Level E                           GPP                                                         2010;95(7):3360-7.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                                30
Chapter 11: LOW LEVELS OF ALBUMINURIA (FORMERLY MICROALBUMINURIA)

  No     1. NACB 2002                    2. NACB 2011 updated/new             3. Why was it          4. Key references                    5. Study         6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its              necessary to           supporting the new                   design           evidence        evidence
                      (1)
         and its grade                   grade and quality of                 modify the             recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                             recommendation?                                                              moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                                                                                           (3)
  WHEN TESTING FOR LOW LEVELS OF ALBUMINURIA IS INDICATED?                                                                                                                   Priority: 1 (A5, A1-2)
  11.a   Annual microalbumin testing     Annual testing for albuminuria in                           American Diabetes Association.       Guideline        Low             Moderate        There is a higher incidence
                                                                              Clarification
         of patients without clinical    patients without clinical                                   Standards of medical care in         expert opinion                                   of obesity and metabolic
         proteinuria should begin in     proteinuria should begin in                                 diabetes --2010. Diab Care 2010;                                                      derangements that
         pubertal or postpubertal        pubertal or postpubertal                                    33 (Suppl 1):S11-61.                                                                  accompany this problem
         individuals five years after    individuals 5 years after                                                                                                                         including an increase in
         diagnosis of type 1 diabetes    diagnosis of type 1 diabetes and                            Vassalotti JA, et al. Testing for    Position         Low                             cardiovascular risk. Low
         and at the time of diagnosis    at the time of diagnosis of type 2                          chronic kidney disease: a position   statement                                        levels of albuminuria is a risk
         of type 2 diabetes. The role    diabetes, regardless of                                     statement from the National                                                           marker for cardiovascular
         of testing is unclear in        treatment                                                   Kidney Foundation. Am J Kidney                                                        events and predictive of
         patients under treatment        B (moderate)                                                Dis 2007;50 (2):169-180 .                                                             cardiovascular events. This
         with angiotensin-converting                                                                 KDOQI Clinical Practice              Guideline        Moderate                        is especially true in diabetes.
         enzyme inhibitors and in                                                                    Guidelines and Clinical Practice
         those with short life                                                                       Recommendations for Diabetes
         expectancy.                                                                                 and Chronic Kidney Disease. Am J
         Level E                                                                                     Kidney Dis 2007;49 (2 Suppl
                                                                                                     2):S12-154
                                                                                                     Klausen KP, et al. Very low level    Cohort study     Low
                                                                                                     of microalbumin-uria is associated
                                                                                                     with increased risk of death in
                                                                                                     subjects with cardio-vascular or
                                                                                                     cerebro-vascular diseases. J
                                                                                                     Intern.Med. 2006;260 (3):231-237
                                                                                                     Klausen KP, et al. New definition    Observational    Low
                                                                                                     of microalbuminuria in hyper-        study
                                                                                                     tensive subjects: association with
                                                                                                     incident coronary heart disease
                                                                                                     and death. Hypertension 2005;46
                                                                                                     (1):33-37
                                                                                                     Kistorp K, et al. N-terminal pro-    Meta-analysis    Moderate
                                                                                                     brain natriuretic peptide, C-
                                                                                                     reactive protein, and urinary
                                                                                                     albumin levels as predictors of
                                                                                                     mortality and cardiovascular
                                                                                                     events in older adults. JAMA
                                                                                                     2005;293:1609-1616.
                                                                                                     Gansevoort RT, et al. The validity   Observational    Moderate                        Study in the Netherlands of
                                                                                                     of screening based on spot           study                                            more than 30,000 people
                                                                                                     morning urine samples to detect
                                                                                                     subjects with microalbuminuria in
                                                                                                     the general population. Kidney
                                                                                                     Int.Suppl 2005; (94):S28-S35
(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        31
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                      5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                      (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                     design          evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                         (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                 moderate-       moderate-
                                                                                                                                                            low)            low-very low)
                                                                                                     Ibsen H, et al. Reduction in           Post hoc        Moderate                        Post hoc analysis of clinical
                                                                                                     albuminuria translates to reduction    analysis                                        cardiovascular outcome
                                                                                                     in cardiovascular events in                                                            trials
                                                                                                     hypertensive patients: losartan
                                                                                                     intervention for end point reduction
                                                                                                     in hypertension study. Hyper-
                                                                                                     tension 2005;45 (2):198-202
                                                                                                     Arnlov J, et al. Low-grade             Observational   Moderate                        Study of cardiovascular
                                                                                                     albuminuria and incidence of           study                                           outcomes
                                                                                                     cardiovascular disease events in
                                                                                                     nonhypertensive and nondiabetic
                                                                                                     individuals: the Framingham Heart
                                                                                                     Study. Circulation 2005;112
                                                                                                     (7):969-975
                                                                                                     Chobanian AV, et al. Seventh           Guideline       Moderate
                                                                                                     report of the Joint National           statement
                                                                                                     Committee on Prevention,               from NIH
                                                                                                     Detection, Evaluation, and
                                                                                                     Treatment of High Blood Pressure.
                                                                                                     Hypertension. 2003;42 (6):1206-
                                                                                                     1252
                                                                                                     Lepore G, et al. Cost-effectiveness    Cost-           Moderate
                                                                                                     of two screening programs for          effectiveness
                                                                                                     microalbuminuria in type 2             analysis
                                                                                                     diabetes. Diab Care 2002;25
                                                                                                     (11):2103-2104
                                                                                                                                                                            (3)
  WHAT IS THE RELATIONSHIP BETWEEN ALBUMINURIA AND CARDIOVASCULAR OUTCOMES?                                                                                                   Priority: 1 (A5, A1-2)
  11.b                                   Urine albumin at concentrations    New recommendation       G. Pambianco, et al. The               Observational   Moderate        Moderate        This was an observational
                                         30 mg/g creatinine should be                               prediction of major outcomes of        cohort study                                    study in patients with type 1
                                         considered a continuous risk                                type 1 diabetes: a 12-year                                                             diabetes followed for 12
                                         marker for cardiovascular events                            prospective evaluation of three                                                        years.
                                         B (moderate)                                                separate definitions of the
                                                                                                     metabolic syndrome and their
                                                                                                     components and estimated
                                                                                                     glucose disposal rate: the
                                                                                                     Pittsburgh Epidemiology of
                                                                                                     Diabetes Complications Study
                                                                                                     experience. Diab Care
                                                                                                     2007;30(5):1248-1254.
                                                                                                     Klausen KP, et al. Very low level      Cohort study    Moderate
                                                                                                     of microalbuminuria is associated
                                                                                                     with increased risk of death in
                                                                                                     subjects with cardiovascular or
                                                                                                     cerebro-vascular diseases. J
                                                                                                     Intern Med 2006;260 (3):231-237.
(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                           32
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                       5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                       (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                      design          evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                          (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                  moderate-       moderate-
                                                                                                                                                             low)            low-very low)
                                                                                                     Ratto E, et al. Microalbuminuria        Observational   Low                             The study evaluated level of
                                                                                                     and cardiovascular risk                 cohort study                                    microalbuminuria relative to
                                                                                                     assessment in primary                                                                   development of left
                                                                                                     hypertension: should threshold                                                          ventricular hypertrophy; not
                                                                                                     levels be revised? Am J                                                                 cardiovascular outcome
                                                                                                     Hypertension 2006;19 (7):728-734
                                                                                                     Klausen KP, et al. New definition       Observational   Low
                                                                                                     of microalbuminuria in hyperten-        cohort study
                                                                                                     sive subjects: association with
                                                                                                     incident coronary heart disease
                                                                                                     and death. Hypertension 2005;46
                                                                                                     (1):33-37
                                                                                                     K. Wachtell, et al. Albuminuria and     Prospective     High                            This clinical trial evaluated
                                                                                                     cardiovascular risk in hypertensive     randomized                                      changes in albuminuria over
                                                                                                     patients with left ventricular          trial                                           a 5 year period in high risk
                                                                                                     hypertrophy: the LIFE study.                                                            patients for cardiovascular
                                                                                                     Ann.Intern.Med. 2003;139                                                                events all of whom had left
                                                                                                     (11):901-906.                                                                           ventricular hypertrophy.
                                                                                                     R. Rachmani, et al. Considerations      Observational   Moderate                        This was an 8 year follow-up
                                                                                                     about the threshold value of micro-     cohort study                                    of 599 people with diabetes
                                                                                                     albuminuria in patients with                                                            evaluating changes in
                                                                                                     diabetes mellitus: lessons from an                                                      cardiovascular risk markers
                                                                                                     8-year follow-up study of 599                                                           including microalbuminuria
                                                                                                     patients. Diab.Res.Clin. Pract.
                                                                                                     2000;49 (2-3):187-194.
                                                                                                                                                                             (3)
  WHAT ARE THE ANALYTICAL CONSIDERATIONS WHEN TESTING FOR LOW LEVELS OF ALBUMINURIA?                                                                                           Priority: NOT LISTED
  11.c   The analytical CV of            The analytical CV of methods to    No change                Sarafidis PA, et al. A comparative      Randomized      Moderate        Moderate        Comparative studies of
         methods to measure micro-       measure albuminuria should be                               evaluation of various methods for       study                                           different validated assays
         albuminuria should be <15%      <15%                                                        microalbuminuria screening. Am.J
         Level E                         B (moderate)                                                Nephrol. 2008;28 (2):324-329.
                                                                                                     Gansevoort RT, et al. The validity      Observational   Moderate
                                                                                                     of screening based on spot              study
                                                                                                     morning urine samples to detect
                                                                                                     subjects with microalbuminuria in
                                                                                                     the general population. Kidney
                                                                                                     Int.Suppl 2005;(94):S28-S35
                                                                                                     Incerti J, et al. Evaluation of tests   Observational   Moderate
                                                                                                     for microalbuminuria screening in       study
                                                                                                     patients with diabetes. Nephrol
                                                                                                     Dial.Transplant. 2005;20
                                                                                                     (11):2402-2407


(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                         33
  No     1. NACB 2002                      2. NACB 2011 updated/new             3. Why was it             4. Key references                       5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                            (2)             (2)
         recommendation                    recommendation with its              necessary to              supporting the new                      design          evidence        evidence
                      (1)
         and its grade                     grade and quality of                 modify the                recommendation                                          (high-          (high-
                                                    (2)
                                           evidence                             recommendation?                                                                   moderate-       moderate-
                                                                                                                                                                  low)            low-very low)
                                                                                                          Meinhardt U, et al. Microalbumin-       Observational   Moderate
                                                                                                          uria in diabetes mellitus: efficacy     study
                                                                                                          of a new screening method in
                                                                                                          comparison with timed overnight
                                                                                                          urine collection J Diab Compli-
                                                                                                          cations 2003;17 (5):254-257
  11.d   Semiquantitative or qualitative   Semiquantitative or qualitative      No change                 Sarafidis PA,et al. A comparative       Randomized      Moderate        Moderate        Most recent studies do have
         screening tests for               screening tests should be                                      evaluation of various methods for       study                                           >95% for Hemocue and
         microalbuminuria should be        positive in >95% of patients with                              microalbuminuria screening. Am.J                                                        Immunodip but only one
         positive in >95% of patients      albuminuria to be useful for                                   Nephrol. 2008;28 (2):324-329.                                                           study confirmed against
         with microalbuminuria to be       screening. Positive results must                                                                                                                       standard lab for Hemocue
         useful for screening. Positive    be confirmed by analysis in an
         results must be confirmed by      accredited laboratory                                          Shaikh A, et al. Comparison             Analytical      Moderate                        Recommendation
         analysis in an accredited         GPP                                                            between immunoturbidimetry,             study                                           downgraded for indirectness
         laboratory                                                                                       size-exclusion chromatography,                                                          of analytical data to clinical
                                                                                                          and LC-MS to quantify urinary                                                           outcomes
         Level E                                                                                          albumin. Clin Chem 2008;54
                                                                                                          (9):1504-1510
  11.e                                     Currently available dipstick tests   New recommendation        Gansevoort RT, et al. The validity      Observational   Moderate        Moderate        There is no convincing
                                           do not have adequate analytical      according to recent       of screening based on spot              study                                           evidence in multiple studies
                                           sensitivity to detect albuminuria    literature on the topic   morning urine samples to detect                                                         for any specific test
                                           B (moderate)                                                   subjects with microalbuminuria in                                                       achieving >95% diagnostic
                                                                                                          the general population. Kidney                                                          sensitivity in two or more
                                                                                                          Int.Suppl 2005; (94):S28-S35.                                                           different studies.
                                                                                                          Incerti J, et al. Evaluation of tests   Observational   Moderate                        Due to this, no specific
                                                                                                          for microalbuminuria screening in       study                                           screening test can be
                                                                                                          patients with diabetes. Nephrol                                                         recommended. ―Dipstick‖
                                                                                                          Dial. Transplant.                                                                       tests for microalbuminuria
                                                                                                          2005;20(11):2402-2407.                                                                  cannot be recommended as
                                                                                                                                                                                                  replacement for the
                                                                                                          Davidson MB, et al. ImmunoDip:          Observational   Moderate                        quantitative tests.
                                                                                                          an improved screening method for        study
                                                                                                          microalbuminuria. Am J Nephrol
                                                                                                          2004;24:284-8.
                                                                                                          Meinhardt U, et al. Microalbumin-       Observational   Moderate
                                                                                                          uria in diabetes mellitus: efficacy     study
                                                                                                          of a new screening method in
                                                                                                          comparison with timed overnight
                                                                                                          urine collection. J Diab Comp-
                                                                                                          lications 2003;17 (5): 254-257.
                                                                                                          Fernandez Fernandez I, et al.           Observational   Moderate
                                                                                                          Rapid screening test evaluation for     study
                                                                                                          microalbuminuria in diabetes
                                                                                                          mellitus. Acta Diabetol 1998;
                                                                                                          35:199-202
(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                                34
  No     1. NACB 2002                    2. NACB 2011 updated/new           3. Why was it            4. Key references                       5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                       (2)             (2)
         recommendation                  recommendation with its            necessary to             supporting the new                      design          evidence        evidence
                      (1)
         and its grade                   grade and quality of               modify the               recommendation                                          (high-          (high-
                                                  (2)
                                         evidence                           recommendation?                                                                  moderate-       moderate-
                                                                                                                                                             low)            low-very low)
                                                                                                     Leong SO, et al. The use of semi-       Randomized      Moderate
                                                                                                     quantitative urine test-strip (Micral   trial
                                                                                                     Test) for microalbuminuria
                                                                                                     screening in patients with diabetes
                                                                                                     mellitus. Singapore Med J
                                                                                                     1998;39:101-3.
                                                                                                     Poulsen PL, et al. Evaluation of a      Observational   Low
                                                                                                     dipstick test for micro-albuminuria     study
                                                                                                     in three different clinical settings,
                                                                                                     including the correlation with
                                                                                                     urinary albumin excretion rate.
                                                                                                     Diabetes Metab 1992;18:395-400.
                                                                                                                                                                             (3)
  WHAT ARE THE PREANALYTICAL CONSIDERATIONS WHEN TESTING FOR LOW LEVELS OF ALBUMINURIA?                                                                                        Priority: 3 (A3-4)
  11.f   Acceptable samples to test      Acceptable samples to test for     No change, but new       Lambers Heerspink HJ, et al.            Prospective     High            Moderate        The albumin:creatinine ratio
         for increased urinary           increased urinary albumin          evidence supports        Comparison of different measures        cohort                                          is the superior method to
         albumin excretion are timed     excretion are timed collections    recommendation           of urinary protein excretion for                                                        predict renal events in
         (e.g., 12 or 24 hour)           (e.g., 12 or 24 h) for                                      prediction of renal events. J Am                                                        patients with type 2 diabetes
         collections for measurement     measurement of the albumin                                  Soc Nephrol 2010;21:1355-60
         of albumin concentration        concentration and timed or
         and timed or untimed            untimed samples for                                         Ibsen H, et al. Reduction in            Observational   Moderate
         samples for measurement of      measurement of the albumin–                                 albuminuria translates to reduction     study
         the albumin:creatinine ratio.   creatinine ratio                                            in cardiovascular events in
         For screening, an untimed       B (moderate)                                                hypertensive patients: losartan
         sample for albumin                                                                          intervention for end point reduction
         measurement (without                                                                        in hypertension study.
         creatinine) may be                                                                          Hypertension 2005;45:198-202.
         considered if a                                                                             Gansevoort RT, et al. The validity      Observational   Moderate
         concentration cutoff is used                                                                of screening based on spot              study
         that allows high sensitivity                                                                morning urine samples to detect
         for detection of an increased                                                               subjects with microalbuminuria in
         albumin excretion rate.                                                                     the general population. Kidney
         Level E                                                                                     Int.Suppl 2005;(94):S28-S35
                                                                                                     Meinhardt U, et al. Microalbumin-       Observational   Moderate
                                                                                                     uria in diabetes mellitus: efficacy     study
                                                                                                     of a new screening method in
                                                                                                     comparison with timed overnight
                                                                                                     urine collectionJ Diabetes Compli-
                                                                                                     cations 2003;17 (5):254-257
                                                                                                     Hishiki S, et al. Circadian variation   Observational   Low
                                                                                                     of urinary microalbumin excretion       study
                                                                                                     and ambulatory blood pressure in
                                                                                                     patients with essential
                                                                                                     hypertension. J Hypertens
                                                                                                     1998;16:2101-8.

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        35
  No     1. NACB 2002                    2. NACB 2011 updated/new             3. Why was it          4. Key references                     5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                     (2)             (2)
         recommendation                  recommendation with its              necessary to           supporting the new                    design          evidence        evidence
                      (1)
         and its grade                   grade and quality of                 modify the             recommendation                                        (high-          (high-
                                                  (2)
                                         evidence                             recommendation?                                                              moderate-       moderate-
                                                                                                                                                           low)            low-very low)
                                                                                                     Howey JE, et al. Biologic variation   Observational   Moderate
                                                                                                     of urinary albumin: consequences      study
                                                                                                     for analysis, specimen collection,
                                                                                                     interpretation of results, and
                                                                                                     screening programs. Am J Kidney
                                                                                                     Dis 1989;13:35-7.
                                                                                                                                                                           (3)
  WHAT IS THE OPTIMAL TIME OF DAY TO MEASURE ALBUMINURIA?                                                                                                                    Priority: 2 (A2-4)
  11.g                                   The optimal time for spot urine      New recommendation     Witte EC, Lambers Heerspink HJ,       Prospective     Moderate        Low             Collected three different
                                         collection is the early morning.                            de Zeeuw D, Bakker SJ, de Jong        non-                                            urines and analyzed in three
                                         All collections should be at the                            PE, and Gansevoort R. First           randomized                                      different ways. One study
                                         same time of day to minimize                                morning voids are more reliable                                                       only that investigates this
                                         variation. The patient should not                           than spot urine samples to assess                                                     topic. Recommendation
                                         have ingested food within the                               microalbuminuria. J Am.Soc.                                                           downgraded for indirectness
                                         preceding 2 h but should be well                            Nephrol. 2009;20 (2):436-443.                                                         of evidence and lack of more
                                         hydrated (i.e., not volume                                                                                                                        data.
                                         depleted).
                                         GPP
                                                                                                                                                                           (3)
  HOW FREQUENTLY ALBUMINURIA SHOULD BE MEASURED?                                                                                                                             Priority: 1 (A5, A1-2)
  11.h                                   Low urine albumin                    New recommendation     Levey AS, et al. The definition,      Consensus       Moderate        Moderate        Strong consensus of experts
                                         concentrations (i.e., <30 mg/g                              classification and prognosis of       report                                          upgraded the
                                         creatinine) are not associated                              chronic kidney disease: a KDIGO                                                       recommendation
                                         with high cardiovascular risk if                            Controversies Conference report.
                                         the eGFR is >60 mL · min–1 ·                                Kidney Int 2011;in press
                                         (1.73 m2)–1 and the patient is
                                         normotensive. If the eGFR is                                Yuyun MF, et al. Micro-               Prospective     Moderate
                                         <60 mL · min–1 · (1.73 m2)–1                                albuminuria independently predicts    cohort
                                         and/or the level of albuminuria is                          all-cause and cardiovascular
                                         30 mg/g creatinine on a spot                               mortality in a British population:
                                         urine sample, a repeat                                      The European Prospective
                                         measurement should be taken                                 Investigation into Cancer in
                                         within the year to assess change                            Norfolk (EPIC-Norfolk) population
                                         among people with hypertension                              study. Int.J Epidemiol. 2004;33
                                         A (moderate)                                                (1):189-198




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                    36
Chapter 12: MISCELLANEOUS POTENTIALLY IMPORTANT ANALYTES

  No     1. NACB 2002                         2. NACB 2011 updated/new             3. Why was it              4. Key references                      5. Study       6. Level of     7. Quality of   8. Comments
                                                                                                                                                                              (2)             (2)
         recommendation                       recommendation with its              necessary to               supporting the new                     design         evidence        evidence
                      (1)
         and its grade                        grade and quality of                 modify the                 recommendation                                        (high-          (high-
                                                       (2)
                                              evidence                             recommendation?                                                                  moderate-       moderate-
                                                                                                                                                                    low)            low-very low)
                                                                                                                                                                                    (3)
  IS THERE A ROLE FOR MEASUREMENT OF INSULIN AND C-PEPTIDE CONCENTRATIONS TO DISTINGUISH TYPE 1 FROM                                                                                  Priority: 2 (A3-4)
  TYPE 2 DIABETES MELLITUS?
  12.a   There is no role for routine         There is no role for routine         Changed wording.           Rutter MD, et al. Use of Alternative   Cohort study   Moderate        Moderate        Models of predictive
         testing for insulin, C-peptide, or   testing for insulin, C-peptide, or                              thresholds defining insulin                                                           baseline measures of insulin
                                              proinsulin in most patients with     Many groups,
         proinsulin in most patients with                                          including ADA, are         resistance to predict incident type                                                   resistance (which include
         diabetes. Differentiation            diabetes. Differentiation between                               2 diabetes and cardiovascular                                                         measures of insulin) in a
                                              type 1 and type 2 diabetes may       moving beyond the
         between type 1 and type 2                                                 categorical concept        disease. Circulation.                                                                 large population. Surrogate
         diabetes may, in most cases,         be made in most cases on the                                    2008;117:1003-1009.                                                                   IR measures (which all
                                              basis of the clinical presentation   (―diagnosis‖) of
         be made based on the clinical                                             metabolic syndrome to                                                                                            included measures of
         presentation and subsequent          and the subsequent course.                                                                                                                            insulin) had modest
                                              These assays are useful              that of continuous and
         course. There is no role for                                              more global measures                                                                                             performance at the 76th
         measurement of insulin               primarily for research purposes.                                                                                                                      centile, with no threshold
                                              Occasionally, C-peptide              of risk for diabetes and
         concentration in the diagnosis                                            cardiovascular                                                                                                   effects. Prediction was
         of the metabolic syndrome            measurements may help                                                                                                                                 particularly poor for CVD.
                                              distinguish type 1 from type 2       disease.
         because knowledge of this
         value does not alter the             diabetes in ambiguous cases,                                    Wilson PW et al. Prediction of         Cohort study   Moderate                        Models of predictive
         management of these patients.        such as patients who have a                                     incident diabetes mellitus in                                                         baseline values in a large
                                              type 2 phenotype but present in                                 middle-aged adults: The                                                               population. Factors easily
         Level E                              ketoacidosis                                                    Framingham Offspring Study. Arch                                                      obtainable on history, exam,
                                              B (moderate)                                                    Intern Med 2007;167:1068-74.                                                          or standard lab tests
                                                                                                                                                                                                    (glucose, lipids) predicted
                                                                                                                                                                                                    incident DM strongly.
                                                                                                                                                                                                    Addition of more complex
                                                                                                                                                                                                    factors, including fasting
                                                                                                                                                                                                    insulin, did not add
                                                                                                                                                                                                    significantly.
                                                                                                              Despres J-P et al.                     Case-control   Moderate                        Case-control study looking
                                                                                                              Hyperinsulinemia as an                 study                                          at baseline fasting insulin
                                                                                                              independent risk factor for                                                           levels in Quebec Heart
                                                                                                              ischemic heart disease. N Engl J                                                      Study. High fasting insulin
                                                                                                              Med 1996;334:952-7.                                                                   levels appeared to be an
                                                                                                                                                                                                    independent risk factor for
                                                                                                                                                                                                    IHD. However, only
                                                                                                                                                                                                    excluded clinically
                                                                                                                                                                                                    diagnosed DM (in early
                                                                                                                                                                                                    1990s, probably many
                                                                                                                                                                                                    undiagnosed) and did not
                                                                                                                                                                                                    adjust for any measures of
                                                                                                                                                                                                    glycemia or BMI




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                                 37
  No     1. NACB 2002                       2. NACB 2011 updated/new           3. Why was it              4. Key references                      5. Study        6. Level of     7. Quality of   8. Comments
                                                                                                                                                                           (2)             (2)
         recommendation                     recommendation with its            necessary to               supporting the new                     design          evidence        evidence
                      (1)
         and its grade                      grade and quality of               modify the                 recommendation                                         (high-          (high-
                                                     (2)
                                            evidence                           recommendation?                                                                   moderate-       moderate-
                                                                                                                                                                 low)            low-very low)
  12.a   These assays are useful            These assays are useful            New evidence               Balasubramanyam A et al.               Observational   Moderate        Moderate -      Investigation of patients
         primarily for research             primarily for research purposes.   regarding using C-         Accuracy and predictive value of       prognostic/                     low             presenting with ketosis, with
         purposes and, in rare cases,       Occasionally, C-peptide            peptide to clarify         classification schemes for ketosis-    diagnostic                                      absent or preserved C-
         to identify patients with an       measurements may help              diagnosis                  prone diabetes. Diab Care 2006;        study                                           peptide function at one year
         absolute requirement for           distinguish type 1 from type 2                                29:2575-9.                                                                             the outcome.
         insulin before switching to oral   diabetes in ambiguous cases,                                                                                                                         Unclear how direct the
         agents, or to assist patients in   such as patients who have a                                                                                                                          outcome is, whether this is
         obtaining insurance coverage       type 2 phenotype but present in                                                                                                                      better than current care
         for continuous subcutaneous        ketoacidosis.
         infusion pumps.                    B (moderate)
         Level E
         A possible role for                None                               Prior recommendation       American College of Obstetrics         Guideline/      Low             Very low        Prior recommendation was
         measurement of fasting insulin                                        deleted. No evidence       and Gynecology. ACOG practice          Expert                                          also supported by expert
         or the assessment of insulin                                          that this is better than   bulletin. Polycycstic ovary            consensus                                       opinion only
         resistance is in the evaluation                                       clinical evaluation for    syndrome. Number 41, December
         of patients with polycystic                                           signs of insulin           2002. Int J Gynecol Obstet 2003;
         ovary syndrome who may be                                             resistance; not            80:335-48
         candidates for treatment                                              recommended by
         aimed at lowering insulin                                             ACOG or other
         resistance in the absence of                                          groups.
         overt diabetes or glucose
         intolerance
         Level E
                                                                                                                                                                                 (3)
  IS THERE A ROLE FOR MEASUREMENT OF INSULIN CONCENTRATIONS OR INDIRECT MEASURES OF INSULIN RESISTANCE                                                                             Priority: 2 (A3)
  IN THE ASSESSMENT OF PATIENTS’ CARDIOMETABOLIC RISK OR TO DETERMINE USE OF INSULIN SENSITIZING DRUGS IN
  DIABETIC OR NON-DIABETIC PATIENTS?
                                            There is no role for               New recommendation         Rutter MD, et al. Use of Alternative   Cohort study    Moderate        Moderate
  12.b
                                            measurement of insulin                                        thresholds defining insulin
                                            concentration in the assessment                               resistance to predict incident type
                                            of cardiometabolic risk, because                              2 diabetes and cardiovascular
                                            knowledge of this value does not                              disease. Circulation.
                                            alter the management of these                                 2008;117:1003-9.
                                            patients
                                            B (moderate)                                                  Wilson PW et al. Prediction of         Cohort study    Moderate
                                                                                                          incident diabetes mellitus in
                                                                                                          middle-aged adults: The
                                                                                                          Framingham Offspring Study. Arch
                                                                                                          Intern Med 2007;167:1068-74.
                                                                                                          Despres J-P et al.                     Case-control    Moderate
                                                                                                          Hyperinsulinemia as an                 study
                                                                                                          independent risk factor for
                                                                                                          ischemic heart disease. N Engl J
                                                                                                          Med 1996;334:952-7.

(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                              38
  No     1. NACB 2002                    2. NACB 2011 updated/new              3. Why was it         4. Key references                    5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                      (2)             (2)
         recommendation                  recommendation with its               necessary to          supporting the new                   design            evidence        evidence
                      (1)
         and its grade                   grade and quality of                  modify the            recommendation                                         (high-          (high-
                                                  (2)
                                         evidence                              recommendation?                                                              moderate-       moderate-
                                                                                                                                                            low)            low-very low)
                                                                                                                                                                            (3)
  DO INSULIN MEASUREMENTS NEED TO BE HARMONIZED?                                                                                                                              Priority: 2 (A3)
                                         Because current measures of                                 Staten M, et al, for the Insulin     Expert            Low             Low             Commentary summarizes
  12.c
                                         insulin are poorly harmonized, a                            Standardization Workgroup.           consensus                                         the above papers and calls
                                         standardized insulin assay                                  Insulin assay standardization:                                                         for a standardized insulin
                                         should be developed to                                      leading to measures of insulin                                                         assay based on above.
                                         encourage the development of                                sensitivity and secretion for
                                         measures of insulin sensitivity                             practical clinical care. Diab Care
                                         that will be practical for clinical                         2010;33:205-6
                                         care
                                         GPP                                                         Miller WG, et al for the Insulin     Investigation     Moderate                        Most assays can achieve
                                                                                                     Standardization Work Group.          of alternate                                      consistent performance with
                                                                                                     Toward standardization of insulin    preparation for                                   calibration traceability based
                                                                                                     immunoassays. Clin Chem              insulin                                           on individual serum samples
                                                                                                     2009;55:1011-8                       reference                                         with insulin concentrations
                                                                                                                                          materials                                         set by isotope dilution mass
                                                                                                                                                                                            spectrometry.
                                                                                                     Marcovina S, et al.                  Comparison of     Moderate                        Current FDA-approved
                                                                                                     Standardization of insulin           different                                         commercially available
                                                                                                     immunoassays: report of the          insulin assays                                    insulin assays provide a
                                                                                                     American Diabetes Association        currently on                                      wide range of values for the
                                                                                                     Workgroup. Clin Chem 2007;           the market in                                     same samples. There clearly
                                                                                                     53:711-6                             the US.                                           is a need to standardize the
                                                                                                                                                                                            reference system and
                                                                                                                                                                                            protocols to enable all
                                                                                                                                                                                            assays to achieve consistent
                                                                                                                                                                                            and uniform results and to
                                                                                                                                                                                            report insulin in identical
                                                                                                                                                                                            units.




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                        39
  No     1. NACB 2002                        2. NACB 2011 updated/new            3. Why was it             4. Key references                     5. Study          6. Level of     7. Quality of   8. Comments
                                                                                                                                                                             (2)             (2)
         recommendation                      recommendation with its             necessary to              supporting the new                    design            evidence        evidence
                      (1)
         and its grade                       grade and quality of                modify the                recommendation                                          (high-          (high-
                                                      (2)
                                             evidence                            recommendation?                                                                   moderate-       moderate-
                                                                                                                                                                   low)            low-very low)
                                                                                                                                                                                   (3)
  IS THERE A ROLE FOR INSULIN AUTOANTIBODY TESTING IN MANAGING PATIENTS WITH DIABETES MELLITUS?                                                                                      Priority: NOT LISTED
  12.d   There is no published               There is no published evidence      No change                 Bingley PJ,et al. Measurement of      Analytical test   Moderate        Very low        International workshops
         evidence to support the use of      to support the use of insulin                                 islet cell antibodies in the Type 1   evaluation                                        using serum exchange
         insulin antibody testing for        antibody testing for routine care                             Diabetes Genetics Consortium:                                                           exercises provide measures
         routine care of patients with       of patients with diabetes.                                    efforts to harmonize procedures                                                         of inter-laboratory variation.
         diabetes                            C (very low)                                                  among the laboratories. Clin Trials                                                     Standardization was
         Level E                                                                                           2010;7(1 Suppl):S56-64.                                                                 possible between three
                                                                                                           Bonifacio E, et al Harmonization of   Analytical test   Moderate                        expert laboratories.
                                                                                                           glutamic acid decarboxylase and       evaluation                                        Quality of evidence and
                                                                                                           islet antigen-2 autoantibody                                                            strength of recommendation
                                                                                                           assays for national institute of                                                        are downgraded for
                                                                                                           diabetes and digestive and kidney                                                       indirectness.
                                                                                                           diseases consortia. J Clin Endocri-
                                                                                                           nol Metab. 2010;95(7):3360-7.
                                                                                                           Törn C, et al. Participating          Analytical test   Moderate
                                                                                                           Laboratories. Diabetes Antibody       evaluation
                                                                                                           Standardization Program:
                                                                                                           evaluation of assays for
                                                                                                           autoantibodies to glutamic acid
                                                                                                           decarboxylase and islet antigen-2.
                                                                                                           Diabetologia. 2008;51(5):846-52.
                                                                                                                                                                                   (3)
  IS THERE A ROLE FOR AMYLIN AND LEPTIN TESTING IN MANAGING PATIENTS WITH DIABETES MELLITUS?                                                                                         Priority: NOT LISTED
         Assays for amylin are not           None                                The evidence
         clinically useful in the                                                accumulated in the
         management of diabetes.                                                 last six to seven years
         These studies should be                                                 has failed to identify
         confined to the research                                                any clinical value in
         setting                                                                 measuring these
         Level E                                                                 analytes in patients
                                                                                 with diabetes.
         Routine measurement of              None                                Recommendation
         plasma leptin concentrations is                                         removed for reasons
         not of value at this time for the                                       mentioned above
         evaluation or management of
         patients with diabetes or
         obesity
         Level E




(1)
     Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.
(2)
    Explanations for grading the level and quality of evidence and for grades of recommendations are given in Supplementary Table 4-5.
(3)
    For priority codes, see SupplementaryTable 2.                                                                                                                                                                               40

								
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