2. Utility of CGMS as a Measure of Glycemic Control in Children with Type 1 Diabetes (T1DM) Rosanna Fiallo-Scharer, MD for

3. Background: DirecNet Diabetes Research in Children Network NIH funded collaborative study group 5 clinical centers, central laboratory, coordinating center, and representatives from NICHD and NIDDK Objective: to critically evaluate the clinical usefulness of current and future glucose sensors in children and adolescents

4. DirecNet Outpatient Randomized Clinical Trial (RCT) 6-month RCT to assess the merits of the GlucoWatch G2 ® Biographer (Cygnus Inc.; Redwood City, CA) in children ages 7-17 years with type 1 diabetes

5. Initial outpatient evaluations of glycemic control prior to randomization included: –48-72 hr CGMS (Medtronic MiniMed) profile. – 8-point SMBG testing while simultaneously wearing a CGMS for 2-3 days using the One Touch UltraSmart (Life scan) meter. –HbA1c measured by HPLC in a central laboratory. Purpose: To examine and compare the results obtained by these baseline measures of glycemic control in a large sample of children and adolescents with T1DM.

6. Methods Analysis included 183 patients who completed the following: –At least 10 Ultra measurements during 2 days of 8- point testing. –40 total hours of CGMS use. –At least one day of overlap between 8-point testing and CGMS use. Ultra plasma glucose levels used as reference values for assessment of accuracy of hypoglycemic detection by the CGMS.

7. Demographic and Clinical Characteristics of 183 Subjects Male/Female 52%/48% Age 12.5 ± 2.8 years Minorities 14% Duration of Diabetes 5.4 ± 3.3 years Injections/Pump54%/46%

8. Number of Glucose Measurements Ultra3,408 CGMS170,381

9. UltraCGMS Mean Ultra and CGMS glucose values Mean (± SD) A1c value was 8.0% ± 0.9%

10. Results were similar for pre- and post-prandial and bedtime. Percent Glucose Values in Range, Below Range and Above Range

11. Mean Glucose Values by Time of Day Ultra CGMS Mean ± 1 SD

12. Mean Ultra Glucose Values by A1c With regression line and 95% confidence limits Spearman correlation = 0.44 P-value < 0.001

13. Mean CGMS Glucose Values by A1c With regression line and 95% confidence limits Spearman correlation = 0.44 P-value < 0.001

14. Slopes of Regression Lines 8-point testing: –26 mg/dl per 1.0% change in A1c CGMS: –22 mg/dl per 1.0% change in A1c

15. CGMS and Ultra During Hypoglycemia Ultra > 70 Ultra 61-70 Ultra ≤ 60 136 CGMS hypoglycemia episodes * Hypoglycemia = two values  60 mg/dl without an intermediate value >70 mg/dl 80 ULTRA hypoglycemia episodes * Hypoglycemia = BG value  60 mg/dl CGMS ≤ 60 CGMS > 70 CGMS 61-70 32% 33% 35% Sensitivity defined as CGMS ≤ 70 within ± 30 minutes; False positive defined as Ultra > 70. 10% 11% 79%

16. CGMS and Ultra During Overnight Hypoglycemia Ultra > 70 Ultra 61-70 Ultra ≤ 60 17 CGMS episodes * Hypoglycemia = two values  60 mg/dl without an intermediate value >70 mg/dl 5 ULTRA episodes * Hypoglycemia = BG value  60 mg/dl CGMS ≤ 60 CGMS > 70 CGMS 61-70 59% 29% 12% Sensitivity defined as CGMS ≤ 70 within ± 30 minutes; False positive defined as Ultra > 70. 40% 20% 40%

17. Summary 8-point testing and CGMS were similar in detection of hyperglycemia and normoglycemia, and in their correlation to A1c values. One-third of CGMS defined hypoglycemia episodes overall and over half overnight could not be confirmed by the home glucose meter.

18. Conclusions 8-point testing and the CGMS provide useful short-term measure of glucose control in youth with type 1 diabetes Both methods have limitations for determining the true rate of hypoglycemia in these patients

19. Conclusions Limitations of 8-point testing: –Compliance –Limited number of values Limitations of CGMS –Retrospective data –Inaccuracy of low glucose measurements

20. Barbara Davis Center –H. Peter Chase –Rosanna Fiallo-Scharer –Jennifer Fisher –Barb Tallant University of Iowa –Eva Tsalikian –Michael Tansey –Linda Larson –Julie Coffey –Amy Sheehan Nemours Children’s Clinic –Tim Wysocki –Nelly Mauras –Larry Fox –Keisha Bird –Kelly Lofton Stanford University –Bruce Buckingham –Darrell Wilson –Jennifer Block –Paula Clinton Yale University –William Tamborlane –Stuart Weinzimer –Elizabeth Doyle –Kristin Sikes –Amy Steffen Jaeb Center for Health Research –Roy Beck –Katrina Ruedy –Craig Kollman –Dongyuan Xing –Cynthia Silvester