1. Diabetes Research in Children Network Pilot Study of the Navigator TM Continuous Glucose Monitoring System in Children with Type 1 Diabetes: Safety, Tolerability, and Factors Associated with Use Stuart A Weinzimer, MD for the Diabetes Research in Children Network Study Group 26 Oct 2007 New Haven, CT

2. Background Real-time continuous glucose monitoring devices (CGM) are a potentially powerful tool in the management of type 1 diabetes (T1D) For successful adoption into clinical practice, however, they must be accurate, comfortable to wear, and easy to use, particularly in children A previous-generation CGM, the GlucoWatch Biographer, failed to improve glycemic control in 200 children with T1D during a 6-mth trial

3. Objectives The aims of this pilot study were to examine the tolerability and effectiveness of a continuous glucose monitor (Abbott Navigator) in children with type 1 diabetes using intensive insulin regimens –CSII (insulin pump therapy) –Glargine-based multiple daily injection (MDI) To identify demographic and/or clinical factors predictive of successful long-term use of CGM

4. Study Design Subjects wore the Navigator as an outpatient for 1 week but were blinded to sensor data in order to characterize “baseline” control Subjects wore the Navigator (unblinded) as an outpatient for 13 weeks Devices were downloaded weekly to subjects’ home computers and subjects were contacted frequently (q1-4wk) in order to monitor Navigator use CGM Satisfaction questionnaires were completed at baseline and 13 weeks Subjects then invited to continue use of Navigator for additional 13 weeks

5. Outcome Measures Glycemic control –Hemoglobin A1c –Mean glucose levels –Percentage of glucose values within, above, or below target Glycemic variability –Mean amplitude of glycemic excursion (MAGE) Tolerability –Continuous Glucose Satisfaction Scale

6. Measures interstitial glucose levels Requires calibration using fingerstick blood glucose at 10, 12, 24 and 72 hours after insertion After a 10-hr warm-up, provides glucose readings every 60 seconds for up to 120 hours Operating range 20 - 500 mg/dL Displays a trend arrow indicating glucose rate of change Alarms for actual or impending high or low glucose levels Abbott Navigator TM

7. Study Subjects – Phase II CSIIMDIp-value N (13-week Phase)3027 N (extension to 26 wk)2421 Age (y)11.1 ± 3.710.3 ± 3.70.62 Female8 (33%)10 (48%)0.37 T1D duration (y)6.1 ± 3.33.5 ± 1.80.005 HbA1c (%)7.1 ± 0.77.8 ± 0.90.01 Mean Glucose (mg/dL)178 ± 27190 ± 330.14 MAGE (mg/dL)126 ± 32151 ± 440.06

8. 0 40 80 120 160 200 CSII MDI Navigator Use (hours/week) Results – Sensor Use BL5-89-1322-261-414-1718-21 # subjects with zero use: 0 0 0 0 1 4 2 0 0 1 0 5 5 3

9. 6.0 7.0 8.0 9.0 CSII MDI HbA1c (%) BaselineWk 7Wk 13Wk 26 Results – Glycemic Control

10. 140 160 180 200 220 CSII MDI BL5-89-1322-261-414-1718-21 Mean Blood Glucose (mg/dL)

11. 30% 40% 50% 60% 70% 80% CSII MDI BL5-89-1322-26 Percentage sensor Glucose Values In Target Range (71-180 mg/dL) Results – Glycemic Targets 1-414-1718-21

12. 0% 2% 4% 6% 8% Results – Hypoglycemia (MDI) Percentage sensor Glucose Values Below Target Range (< 70 mg/dL) BL5-89-1322-261-414-1718-21 CSII MDI

13. 80 100 120 140 160 CSII MDI BL5-89-1322-26 Results – Glycemic Variability 1-414-1718-21 Mean Amplitude of Glycemic Excursion (MAGE, mg/dL)

14. Capillary Blood Glucose Testing Need a graph like others showing meter use (tests/day) over course of study

15. CGM Satisfaction 13 Wk26 Wk CSII – Subject – Parent 3.6  ?? 3.9  ?? Need values MDI – Subject – Parent 3.5  0.5 3.8  0.4 3.6  0.5 3.8  0.5 Scores are out of a 5 point Likert scale

16. Factors Predictive of Continued Use can be like table from paper, but need p-values

17. Conclusions Navigator was well-tolerated in pediatric subjects using either CSII or glargine-based basal-bolus MDI over 26 weeks Decrease in sensor use over time Early improvements in A1c, percentage of glucose levels in range, and glycemic variability No baseline factors were predictive of successful extended use Short-term use, early drop in HbA1c, and higher levels of CGM satisfaction predict successful extended use

18. Barbara Davis Center –H. Peter Chase –Rosanna Fiallo-Scharer –Laurel Messer –Barbara Tallant University of Iowa –Eva Tsalikian –Michael Tansey –Linda Larson –Julie Coffey –Joanne Cabbage Nemours Children’s Clinic –Tim Wysocki –Nelly Mauras –Larry Fox –Keisha Bird –Kim Englert Stanford University –Bruce Buckingham –Darrell Wilson –Jennifer Block –Paula Clinton Yale University –William Tamborlane –Stuart Weinzimer –Brett Ives –Amy Steffen Jaeb Center for Health Research –Roy Beck –Katrina Ruedy –Craig Kollman –Dongyuan Xing –Cynthia Stockdale

19. The following slides are just audience questions

20. Audience Question 1: (before presentation) On a scale of 1 (lowest) to 5 (highest), how would you rate the tolerability of continuous glucose sensors in the management of children with diabetes ? –1. Completely intolerable –2. Somewhat intolerable –3. Neither tolerable nor intolerable –4. Somewhat tolerable –5. Very tolerable

21. Audience Question 2: (before presentation) On a scale of 1 (lowest) to 5 (highest), how would you rate the usefulness of continuous glucose sensors in the management of children with diabetes ? –1. Completely useless –2. Somewhat useless –3. Neither useful nor useless –4. Somewhat useful –5. Very useful

22. Audience Question 3: (before presentation) On a scale of 1 (lowest) to 5 (highest), how likely would you be to recommend the use of continuous glucose sensors in the management of children with diabetes ? –1. Very unlikely –2. Somewhat unlikely –3. Neither unlikely nor likely –4. Somewhat likely –5. Very likely

23. Audience Question 1: (after presentation) On a scale of 1 (lowest) to 5 (highest), how would you rate the tolerability of continuous glucose sensors in the management of children with diabetes ? –1. Completely intolerable –2. Somewhat intolerable –3. Neither tolerable nor intolerable –4. Somewhat tolerable –5. Very tolerable

24. Audience Question 2: (after presentation) On a scale of 1 (lowest) to 5 (highest), how would you rate the usefulness of continuous glucose sensors in the management of children with diabetes ? –1. Completely useless –2. Somewhat useless –3. Neither useful nor useless –4. Somewhat useful –5. Very useful

25. Audience Question 3: (after presentation) On a scale of 1 (lowest) to 5 (highest), how likely would you be to recommend the use of continuous glucose sensors in the management of children with diabetes ? –1. Very unlikely –2. Somewhat unlikely –3. Neither unlikely nor likely –4. Somewhat likely –5. Very likely