Practical Ways to Achieve Targets in Diabetes Care

DAVID C KLONOFF, MD Medical Director Dorothy L. and James E. Frank Diabetes Research Institute of Mills-Peninsula Health Services Clinical Professor of Medicine, UCSF GLUCOSE SENSORS IN ACHIEVING TARGET A1C AUGUST 13, 2005 KEYSTONE RESORT San Francisco Mills Health Center San Mateo, California Spring, 1999 Vol. 1, No. 1 ISSN 1520-9156 A SENSOR IS A DEVICE THAT DETECTS OR SENSES A SIGNAL AND CAN MEASURE GLUCOSE INTERMITTENTLY IN BLOOD OR CONTINUOUSLY IN ISF Three Waves of Technology in Diabetes Monitoring (1) Urine Testing (2) Intermittent Blood Glucose Testing (3) Continuous Glucose Monitoring INTERMITTENT BLOOD GLUCOSE SENSORS IN ACHIEVING TARGET A1C CURRENT STATUS  Improves control in T1DM and insulin-treated T2DM  Generally does not improve control in T2DM on diet or OHAs  Prevents severe hypos in all pts  Works best if pts know to respond ASSOCIATION BETWEEN FREQUENCY OF SMBG TESTING AND A1c IN T1DM 10 9.5 9 8.5 8 7.5 7 6.5 6 5.5 5 A1c = 5.99 + 5.32 / ([number of glucose tests per day] + 1.39) A1c (%) n=378 0 2 4 6 8 10 12 SMBG Tests per Day 378 T1DM INSULIN PUMP USERS Davidson et al. Diabetes 2004; 53 (Suppl 2): A101 SMBG FREQUENCY CORRELATES WITH A1C ADJUSTED FOR DEMOGRAPHIC VARIABLES A1c (%) For full adherence D A1C = 1.0% in T1 DM 0.6% in T2 DM P < .0001 No r values calculated 24,312 Kaiser Northern Calif adults (95% T2 / 5% T1) Karter et al. Am J Med 2001: 111:1-9 SMBG FREQUENCY CORRELATES WITH A1C ADJUSTED FOR DEMOGRAPHIC VARIABLES For each additional SMBG per day - A1c fell by 0.3% A1c (%) For full adherence D A1C = 1.0% in T1 DM 0.6% in T2 DM P < .0001 No r values calculated 24,312 Kaiser Northern Calif adults (95% T2 / 5% T1) Karter et al. Am J Med 2001: 111:1-9 July 2005 ● Volume 22 ● Pages 200-206 SELFMONITORING OF BLOOD GLUCOSE IN NON-INSULIN-TREATED DIABETIC PATIENTS: A LONGITUDINAL EVALUATION OF ITS IMPACT ON METABOLIC CONTROL M. Franciosi, F. Pellegrini, G. De Berardis, M. Belfiglio, B. Di Nardo, S. Greenfield, S. H. Kaplan, M. C. E. Rossi, M. Sacco, G. Tognoni, M. Valentini and A. Nicolucci for The QuED Study Group quality of care and outcomes in Type 2 diabetes 1896 T2DM non-insulin-treated patients followed for 3 years Freq of SMBG did not predict better control but did predict fewer hypoglycemic episodes THE DiGEMtrial PROTOCOL A 12-MONTH RCT IN T2DM TO DETERMINE THE EFFECT OF 3 STRATEGIES OF SMBG ON CONTROL 450 T2DM PATIENTS ON OHAs OR DIET 1 CONTROL Rx: Q 3 MO A1c WITH NP INTERPRETATION 2 3 SMBG WITH ADJUSTMENTS IN Rx PER NP ONLY STUDY TO REPORT IN 2007 SMBG WITH ADJUSTMENTS IN Rx PER SUBJECT OR NP BMC Fam Pract 6: 25; 2005 CONTINUOUS GLUCOSE SENSORS IN ACHIEVING TARGET A1C CURRENT STATUS  Provides around-the-clock info on absolute BG values and trends  Five products now approved and two are being evaluated by the FDA  Greater accuracy needed  Reimbursement is inconsistent CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends PURPOSE OF CONTINUOUS GLUCOSE MONITORING To obtain maximal information about shifting blood glucose levels throughout the day to make the best treatment decisions CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends CONTINUOUS GLUCOSE MEASUREMENT DEVICES APPROVED PRODUCTS IN US & EUROPE  Continuous Glucose Monitoring     System Gold (CGMS Gold) Guardian Guardian RT * (Europe only) GlucoWatch® G2 Biographer GlucoDay * (Europe only) CONTINUOUS GLUCOSE MONITORING SYSTEM GOLD (CGMS GOLD) CGMS GOLD - CONTINUOUS GLUCOSE MONITORING SYSTEM GLUCOSE SENSOR MONITOR COM-STATION TO DOWNLOAD DATA SENSERTER MEDTRONIC MINIMED GUARDIAN AND GUARDIAN RT MEDTRONIC MINIMED GUARDIAN COMPONENTS Sensor Transmitter Monitor Alarm (50 db) ® GLUCOWATCH G2 BIOGRAPHER TIME GLUCOSE TREND MENARINI GLUCODAY CONTINUOUS GLUCOSE MONITOR GLUCODAY ITALY ABBOTT LABORATORIES FREESTYLE NAVIGATOR Abbott Laboratories FreeStyle Navigator™ Continuous Glucose Monitor FEATURES 1 Enzyme-tipped SC catheter 2 Wireless transmission to monitor up to 10 ft away 3 Reads Q 1 min in real time 4 Sensor lasts 3 days DEPLOYMENT OF THE NAVIGATOR 1 Attach Sensor Mount to Skin 2 Press to Insert Sensor 3 4 Attach Transmitter to Sensor Mount Data is Transmitted to Receiver DEXCOM SHORT-TERM CONTINUOUS GLUCOSE MONITORING SYSTEM (STS) CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Problems A TOOL FOR DETERMINING ACCURACY IN AN EXPERIMENTAL BLOOD GLUCOSE MONITOR RELATIVE ABSOLUTE DIFFERENCE (RAD) = I EXPERIMENTAL BG – REFERENCE BG I x REFERENCE BG RAD IS EXPRESSED AS A PERCENTAGE 1 100 CONTINUOUS GLUCOSE MONITORING ACCURACY STUDIES BY DIRECNET  RAD of CGMS 19%  RAD of CGMS Gold 11% & 12%  RAD of GW2B 16% 91 and 89 children with T1DM in a CRC setting DirecNet: Diabetes Technol Ther 2003; 5: 781-789 and 791-800 200 children with T1DM in an outpatient setting DirecNet: Diabetes Technol Ther 2005; 7:109-114 A TOOL FOR DETERMINING ACCURACY IN AN EXPERIMENTAL BLOOD GLUCOSE MONITOR INTERNATIONAL ORGANIZATION FOR STANDARDIZATION (ISO) CRITERIA  Ref BG > 75 mg/dl: Sensor BG +/- 20%  Ref BG < 75 mg/dl: Sensor BG +/- 15 mg/dl  Data expressed as % of pairs meeting above criteria ISO ACCURACY OF CONTINUOUS BG MONITORS % of Values Meeting ISO Criteria One Touch Ultra CGMS Gold GW2B Reference Glucose Values (mg/dl) DirecNet: Diabetes Technol Ther 2003; 5: 781-789 and 791-800 EIGHT-POINT TESTING VS CGMS TO EVALUATE CONTROL IN T1DM EIGHT-POINT TESTING ADVANTAGES CGMS MONITOR ADVANTAGES Children with T1DM n = 200 JCEM 2005; 90: 3387-3391  Similar Mean BGs:     188 mg/dl 183 mg/dl Mean noc BG: 199 mg/dl 174 mg/dl ? ↑ specificity low BG ? ↓ specificity low BG Similar BG / A1c ratios: 23 mg/dl per 1% A1c 19/mg/dl per 1% A1c 2-hr PP ∆BG PM: 2-hr PP ∆BG PM: + Compliance (72h): 10% Compliance Median: 70h CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends SITUATIONS REQUIRING DETAILED INFO ABOUT GLUCOSE FLUCTUATIONS CLINICAL INDICATIONS TO USE CGM  Assess impact of an adjustment in therapy to improve control  Achieve tighter control without causing hypoglycemia (e.g. peds DM, GDM, ICU)  Diagnose / prevent hypoglycemia during sleep or hypoglycemia unawareness  Quantify the response in clinical trials ELEMENTS OF THERAPY THAT CAN BE ADJUSTED WITH CGM  Type or dose of mealtime insulin  Type or dose of basal insulin  Treatment of High or Low BG  Insulin: Glucose ratio for High BGs  Insulin: CH2O ratio at mealtime  Carbohydrate composition of diet  Discount in short-acting ins for exercise  HS regimen because of dawn phenom  Target pre- or post- prandial BG  Refer to Ψ to improve adherence ELEMENTS OF THERAPY THAT CAN BE ADJUSTED WITH CGM  Increase dose of mealtime insulin (#1 of 8) I  Type of basal insulin . (#1 of 9)  Treatment of High or Low BG  Insulin: Glucose ratio for High BGs  Insulin: CH2O ratio at mealtime  Carbohydrate composition of diet  Discount in short-acting ins for exercise  HS regimen because of dawn phenom  Target pre- or post- prandial BG Sabbah et al: Diabetes 2000; 49 (Suppl  Refer to Ψ to improve adherence 1): A393 Kaufman et al: Diabetes Care 2001; 24: 2430-2434 CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends OUTCOMES TRIALS OF CGM: STUDY DESIGNS AND ENDPOINTS  Six RCT’s: two showed SS ↓ in A1c, three showed NSS ↓ in A1c and one showed no ↓ in A1c but did show a SS ↓ in duration of hypo episodes  Five nonrandomized uncontrolled trials: all five showed a SS ↓ in A1c  One nonrandomized uncontrolled trial using ↓ and ↑ excursions as an endpoint showed reduced excursions of both IMPROVED BG CONTROL WITH REAL TIME CONTINUOUS GLUCOSE MONITORING USING AN IMPLANTED SENSOR 10 BLINDED TESTING vs REAL TIME ACCESS Time Spent (hrs/day) 8 6 BLINDED TESTING REAL TIME ACCESS Time spent Hypoglycemic (< 55 mg/dl) Decreased 47% Time spent Hyperglycemic (> 241 mg/dl ) Decreased 25% 4 2 0 40 - 55 56 - 80 81 – 140 141 – 240 241 - 400 Diabetes Care. 2004;27:734-8 Glucose Range (mg/dl) SUMMARY 20 T1DM subjects at Stanford and Barbara Davis Center wore 1-2 GlucoWatch GW2Bs 240 total alarms in 24 hours (180 during sleep) for: a) BG ≤ 70 mg/dl b) expected hypo within 20 min c) BG ≥ 300 mg/dl Subjects awoke to: 29% of individual alarms 66% of alarm events 100% of true hypo events DirecNet: Diabetes Technol Ther June 2005; 7:440-447 SUMMARY 20 T1DM subjects at Stanford and Barbara Davis Center wore 1-2 GlucoWatch GW2Bs 240 total alarms in 24 hours (180 during sleep) for: a) BG ≤ 70 mg/dl b) expected hypo within 20 min c) BG ≥ 300 mg/dl Subjects awoke to: 29% of individual alarms 66% of alarm events 100% of true hypo events DirecNet: Diabetes Technol Ther June 2005; 7:440-447 CONTINUOUS GLUCOSE MONITORING OUTLINE  Purpose  Technologies  Target Populations  Accuracy  Clinical Indications  Outcomes  Future Trends MEDTRONIC MINIMED PARADIGM SENSOR AUGMENTED SYSTEM CONTINUOUS REAL TIME SENSOR TRANSMITTER COMBINED MONITOR AND INSULIN PUMP MONITOR SENSOR SUTURES CABLE Diabetes Technol Ther 2002; 4: 305-312 J Feline Med Surg 2005; 7: 53-62 J Feline Med Surg 2005; 7: 53-62 J Feline Med Surg 2005; 7: 53-62 J Feline Med Surg 2005; 7: 53-62 J Feline Med Surg 2005; 7: 53-62 J Feline Med Surg 2005; 7: 53-62 CONTINUOUS GLUCOSE MONITORING MEANS MORE BLOOD GLUCOSE DATA CONTINUOUS GLUCOSE SENSORS IN ACHIEVING TARGET A1C CONCLUSIONS  Provides maximal information for making treatment decisions  Multiple methods are effective  Technology will be a routine part of intensive treatment regimens  In the future a continuous sensor will control an artificial pancreas