Cystic Fibrosis Related Diabetes An Update

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Cystic Fibrosis Related Diabetes An Update Powered By Docstoc
					Julie Matel, MS, RD, CDE
Cystic Fibrosis Related Diabetes

 Type 1: lack of insulin   Type 2: insulin resistance/
        secretion          decreased insulin secretion
CFRD Is a Distinct Form of Diabetes
                              Type 1        Type 2        CFRD

Most common age of onset       <20            >40           22-24
Usual body habitus             Normal         Obese         Normal
Insulin Secretion              Absent         ↓             ↓
Insulin Sensitivity            ↓              ↓↓↓           ↓
Autoimmune etiology            Yes            No            No
Ketoacidosis                   Yes            Rare          Rare
Microvascular complications    Yes            Yes           Yes
Macrovascular complications    Yes            Yes           No

                               Moran A, et al. Diabetes Res Clin Pract. 1999.
Microvascular Complications in Subjects
with Diabetes > 10 Years Duration
 98 patients with CFRD with FH, 39 patients >10 yrs duration

    Complication               CFRD                   T1D/T2D
 Retinopathy                    15%                         60%
 Nephropathy                    16%                      20-30%
 Neuropathy                     50%                         50%
 Gastropathy                    50%                       50%
 Macrovascular                  0%                        ~60%
                                Schwarzenberg, Moran et al. Diabetes Care. 2007
Clinical Signs and Symptoms of
Diabetes in CF
  Excessive thirst or excessive urination

  Failure to gain or maintain weight despite nutritional
  Failure to grow

  Delayed progression of puberty

  Chronic decline in pulmonary function

                                 Moran A, et al. Diabetes Res Clin Pract. 1999.
Decline in Pulmonary Functions and Nutritional
Status Precedes Development of Diabetes

 “Prediabetic state may be deleterious because a greater
  decline in pulmonary function and nutritional state
  was found as early as 6 years before the diagnosis of

                   Bismuth, E. et al J Pediatr 2008;152:540-5
CFRD has an impact on patient outcomes…
    Reduced survival
      In a study of 448 people with CF, less than 25% with
      diabetes survived to age 30, whereas nearly 60% of
      people without diabetes reached this age
                                   Finkelstein et al J Pediatr 1988

    Decreased Pulmonary Function
      Cross sectional analysis of 7566 people enrolled in the
      European Epidemiologic Registry of CF found lower
      FEV1% in those with DM vs those without DM at all
      ages (72% vs 52%)
                                   Koch et al Pediatr Pulmonol 2001
Screening for CFRD
  High Risk: Pre- and 2hr post-prandial glucose
    Hospitalized
    Oral or iv corticosteroids
    Pregnancy

  At least annual glucose screening for all patients
  with CF >10 years of age (LPCH >6 years of age)

  Hemoglobin A1c > 6.5 diagnostic for diabetes

  Hemoglobin A1c < 6.5 does not rule out diabetes
   or glucose impairment related to CF
                                  Moran A, et al. Diabetes Res Clin Pract. 1999.
Oral Glucose Tolerance Test
 Fasting, 30 minute, 1 hour, 2 hour blood draws after
  glucose beverage
 Most sensitive way to detect CFRD without fasting
 Early Identification is important
   High risk for progression to fasting hyperglycemia
   High risk for excessive decline in pulmonary function

                                   Moran A, et al. Diabetes Res Clin Pract. 1999.
                                Milla CE, et al. Am J Respir Crit Care Med. 2000.
Glucose Tolerance Categories in CF with
  Normal Glucose Impaired    CFRD without    CFRD with
  Tolerance      Glucose     Fasting         Fasting
                 Tolerance   Hyperglycemia   Hyperglycemia

  FBG:        FBG:       FBG:       FBG:
  < 100 mg/dl <100 mg/dl <100 mg/dl >126 mg/dl

  2 hour post 2 hour post    2 hour post 2 hour post
  prandial:   prandial:      prandial:   prandial:
  <140 mg/dl 141-199         >200 mg/dl >200 mg/dl
Glucose Tolerance Prevalence in
Patients with CF

                               80               36
          Percent Prevalence

          Within Age Group

                                                                     38        27

                                     34                              20
                               20               15
                                                11                   15        16
                                0          3
                                     5-9       10-19             20-29        30+
                                                       Age (years)
 Normal glucose tolerance

 Impaired glucose tolerance
 CFRD without fasting hyperglycemia                                       Moran A, et al. J Pediatr. 1998.
 CFRD with fasting hyperglycemia
Insulin Secretion is Decreased in CF
Patients With and Without Diabetes
                       Insulin or C-peptide

PS=pancreatic sufficient                      Control   CF-PS CF-no DM CFRD
DM=diabetes mellitus
* P<0.001 vs control
                                                                            Moran A, et al. J Pediatr. 1991.
Metabolic Consequences of Insulin
deficiency in CF

     Malnourished or very sick CF patient are severely
      protein catabolic.
     Healthy, well-nourished CF patients have subtle
      defects in protein and fat breakdown that may
      compromise nutrition.
     Increased protein and fat breakdown can be
      prevented if high enough insulin levels are
      achieved, providing rationale for insulin
      treatment even in the face of relatively normal
      blood glucose levels.

    Moran et al: Diabetes 50:1336-1343,2001
    Hardin et al: Pediatrics 101:433-437,1998
Insulin Therapy to Improve BMI in Cystic Fibrosis-
Related Diabetes Without Fasting Hyperglycemia

  n= 81
  People with CF and CFRD without fasting
   hyperglycemia were treated with insulin vs.
   Repaglinide or placebo
  Insulin group showed improved BMI after one year of
   therapy whereas the group treated with Repaglinide
   did not

                             Moran A. et al. Diabetes Care. 2009.
Goals of Medical Nutrition Therapy
 Achievement of optimal nutritional status
      Provision of sufficient calories
      Calorie restriction is never appropriate
 Near-normalization of blood glucose
      Management of hyperglycemia and hypoglycemia
      Necessary for energy balance
          Insulin is an anabolic hormone
 Flexible meal planning approach to optimize
  energy intake
      Meal plan should be based on usual food intake and patterns
Key Dietary Considerations
 No restrictions on calorie or total carbohydrate intake
 Consistent carbohydrate diets may not be feasible
 Consume high fat diet (35-40% of calories)
 Best option is carbohydrate counting with short acting
  pre-meal insulin to match carbohydrate intake
 Allows adequate calorie intake/flexible schedule
Improved Outcomes with More
Aggressive Management

 Minnesota data
Cystic Fibrosis-Related Diabetes: Current Trends in
Prevalence, Incidence, and Mortality

    Over the past 15 years, > 50% decrease in mortality in
     male and females with diabetes with absence of a sex
    Mortality remains significantly higher in CF patients
     with diabetes compared to those without, but the gap
     has narrowed

                                Moran A. et al. Diabetes Care. 2009.
What does more aggressive
management mean?
Routine screening with annual oral glucose tolerance
 test (OGTT) for patients aged > 6 years
Careful inpatient glucose monitoring and use of
 insulin as needed
Early institution of intensive insulin therapy has
 become more routine in the last 5 years
Pre-meal insulin is prescribed for those with CFRD
 without fasting hyperglycemia
LPCH/Stanford Protocol for
Diabetes Management
 Annual OGTT for patients > 6 years
 Endocrine consult for those with OGTT indicating
  CFRD without fasting hyperglycemia or CFRD
 Inpatient Screening for CFRD
   Monitor fasting BG and 2 hour post meal for 48 hours
    upon admission to the hospital
 Early screening may help identify folks at risk for
  developing glucose abnormalites
 Early treatment of glucose abnormalities may improve
  nutrition and pulmonary outcomes
 New diabetes screening and treatment guidelines are
  being developed by a CFF consensus committee so….
                       Stay Tuned!