1. Practical Aspects of Continuous Glucose Monitoring 2008 Rosanna Fiallo-Scharer, MD Laurel Messer, RN, BSN, CDE Barbara Davis Center for Childhood Diabetes

2. Presentation Outline Historical background Accuracy & research Insurance coverage for pediatrics Barbara Davis Center experience Real-Time and retrospective use of CGM Practical child and family issues

3. CGM Historical Background

4. CGMS® –FDA- approved in 1999 – Retrospective review of downloaded data –Principle: Glucose oxidase-coated subcutaneous sensor Glucowatch Biographer –FDA- approved in 2001 –First approved real time device –Principle: reverse iontophoresis through intact skin

6. Real Time Continuous Glucose Monitoring Freestyle Navigator Dexcom STS Paradigm Real Time System

7. Continuous Glucose Monitors The DirecNet experience

8. Inpatient Accuracy Study Principal Aim: To assess the accuracy of the Medtronic MiniMed CGMS and the GlucoWatch Biographer II vs. gold standard plasma glucose measurements in children with T1DM

9. Subject Demographics 91 Children and Adolescents 91 Children and Adolescents 51% Female 51% Female 43% Pumpers 43% Pumpers Mean HbA1c = 7.8% Mean HbA1c = 7.8%

10. Daily Glucose Variations Procedure Regular meals and insulin doses GS glucose q30-60 min

11. Results nr Mean RAD Median RAD Within ISO GWB 3,6720.86 22%16%80% CGMS (original) 5,6580.77 26%19%53% CGMS (Modified) 1,120 0.90 16%11%72% Ultra2,0680.97 6%9%94% ISO Criteria: If reference glucose ≤ 75 mg/dL, sensor glucose within ± 15 mg/dL; if reference glucose > 75 mg/dL, sensor glucose within ± 20%. Diabetes Technology &Therapeutics Vol 5 (5), 2003

12. Factors NOT Impacting Accuracy For Either the GW or CGMS Age of the Subject BMI (body mass index) Sensor age (CGMS) Location of GWB placement –Upper vs lower arm –Inner vs outer arm

13. Sensor Accuracy by Glucose Level

14. CGMS Sensitivity and False Alarm rate for detection of hypoglycemia Alarm Setting SensitivityFalse Alarm Rate (mg/dl) 6049%58% 8084%64% 100 100%75% 120 100%84%

15. Down alert Only 24% and 8% of truly hypoglycemic incidents were detected by the simple alarm during the hypoglycemia test and overnight, respectively Combining the simple alarm with the down alert improves those sensitivity rates to 88% and 77%, respectively Diabetes Technol Ther. 2004 Oct; 6(5): 559-66

16. Accuracy of the Freestyle Navigator and Guardian RT Diabetes Care. 2007 Jan; 30 (1):59-64

17. Results n Median RAD Within ISO Guardian RT1,43414% 64% Navigator 1,811 12%74% Ultra 2,068 9%94% ISO Criteria: If reference glucose ≤ 75 mg/dL, sensor glucose within ± 15 mg/dL; if reference glucose > 75 mg/dL, sensor glucose within ± 20%.

18. These devices have sufficient accuracy to allow tracking of glucose values However, neither device is as accurate as meters presently available on the market Particularly useful for detecting post- prandial glycemic excursions and overnight glucose trends Conclusions

19. GWB2 Randomized Controlled Trial Diabetes Care. 2005 May; 28(5):1101-6

20. HbA1c

21. Ultra Daily Use First Month:5.1 ± 1.6 in Usual Care group, 5.6 ± 1.7 in GWB group Third Month:5.1 ± 1.8 in Usual Care group, 5.3 ± 1.6 in GWB group Sixth Month:4.8 ± 1.7 in Usual Care group, 5.1 ± 1.7 in GWB group

22. GW2B use First Month:2.1 ± 0.8 uses per week (64% = at least 2 sensors/ week) Third Month: 1.6 ± 0.7 uses per week (7 of the 99 subjects discontinued GW2B use) Sixth Month: 1.5 ± 0.6 uses per week (26 of the 98 subjects discontinued GW2B use) Questionnaire regarding non-use of the GW2B (55 subjects) 76% = “skin irritation” 56% = “skips too frequently” 47% = “alarms too frequently” 33% = “readings not accurate” 31% = “too busy to use it” 22% = “forget to use it” 18% = “did not help with diabetes management”

23. Lesson learned: For CGM to help with diabetes management, patients must use them!

24. Freestyle Navigator Pilot trial Journal Pediatr. 2007 Oct; 151 (4): 388-93

25. Summary 57 pediatric subjects enrolled –30 Pumpers –27 MDI A1c data collected at 13 weeks Voluntary sensor use offered after 13 weeks 73% of pump users continued to use sensor at 12 months and 78% of MDI users continued at 10 months (median hrs/wk 98 and 85 respectively)

26. A Randomized Clinical Trial to Assess the Efficacy of Real- Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes funded by a grant from the Juvenile Diabetes Research Foundation

27. Clinical Trial Design  450 subjects age >=8 years 330 with A1c >7.0% and 120 with HbA1c <7.0% 1/3 in each age group: 8- 25 50% pump users, 50% MDI  Randomization to RT-CGM or Usual Care Navigator, DexCom, Paradigm/Guardian REAL-Time  Primary outcome at 6 months  Months 7-12: both groups use RT-CGM  Outcomes: HbA1c, hypoglycemia, quality of life  Cost-effectiveness ancillary study

28. Current status JDRF RCT 6 month data collection already completed 12 month data collection still in progress.

29. Insurance coverage for pediatrics Currently only one device approved for pediatric use Real time technology not universally covered Some success with approval on case by case basis Usually approved on appeals process

30. Presentation Outline RT- CGM systems for pediatrics Accuracy & research Insurance coverage for pediatrics Barbara Davis Center experience Real-Time and retrospective use of CGM Practical child and family issues

31. Barbara Davis Center experience with CGM Currently: 100+ pediatric pts on CGM 5 years old through adulthood Commercially: Paradigm REAL-Time, Dexcom SEVEN Research: Navigator Varied experiences with devices

32. Using a sensor on daily basis Insert sensor (every 3-7 days) Warm up period with no glucose readings Entering fingerstick BG for calibrations Device starts reading REAL-TIME information Occasional downloading of device for RETROSPECTIVE information

33. Real Time CGM Use SENSOR glucose levels Different from BG levels due to lag time Updates every 1-5 minutes ArrowsAlarms Trend information

34. Real Time CGM Use EDUCATION POINT: –Must always do a BG for insulin, treatment and management decisions WHY? No device currently FDA approved for replacement therapy Sensor may not be reading accurately

35. Retrospective data Downloaded at home or in clinic (anyone have experience with this?)

36. Retrospective data EDUCATION POINTS Must know the WHY before knowing WHAT to change! Make dosing changes if BG/SG is out of range 2 out of 3 days Important to look at trends Look at most recent week Questions before changing: missed bolus? menses? Illness? Bad pump set? Mistake in dose? Sports?

37. Retrospective data Trend graph (sensor daily overlay, modal day)

38. Coming soon: JDRF online CGM school!

39. Pediatric issues Expectations Sensor sticking SportsAlarmsCalibrations Family dynamics

40. Pediatric issues Expectations Expectations No fingerstick BGs Will read from the moment you put on Alarms will prevent all highs and lows Reality: 4-8 BGs per day Periods where not calibrated, not reading Sensor errors for no reason Alarms annoying

41. Pediatric issues Sensor sticking Three main problems: 1) Sensor does not stick Try different types of preps (IV prep, skin prep, Skin Tac, Mastisol, tincture of benzoine 2) Tape or preps causes skin reactions Try different preps or tapes Use IV3000/Tegaderm FIRST, and cut hole for sensor to insert through 3) Not enough skin “real estate” Try different sensors Pinch up even if not indicated Chart on handout Chart on handout

42. Pediatric issues Sensor sticking

43. Placement Consider where least impact and movement Arm– can cover with ace bandage for extra support (take off at night) Sweating Use antiperspirant under tape Breaking Never take CGM receiver out into game Pediatric issues Sports PROBLEM: CGM sensors fall off, sweat off, get broken

44. Calibration reminder * Calibration error * Replace sensor * High Glucose * Low Glucose * Projected Low Glucose * Projected High Glucose * Meter BG Now * Sensor end * W Calibration reminder * Calibration error * Replace sensor * High Glucose * Low Glucose * Projected Low Glucose * Projected High Glucose * Meter BG Now * Sensor end * Weak signal * Disconnected * Low transmitter * Bad transmitter * Sensor error * Bad sensor Pediatric issues Alarms Alarms can become overwhelming/ annoying Why?.... PROBLEM: Alarms can become overwhelming/ annoying Why?....

45. HIGH ALARM: 250-300 mg/dl* LOW ALARM: 70-80 mg/dl Consider higher with hypoglycemia unawareness Can gradually “tighten” alarms as glucose levels get tighter * My opinion only! Pediatric issues Alarms GOAL: Set alarms that are MEANINGFUL and will NOT drive the child crazy!

46. Can I change the type of alarm notice?” Navigator: YES: vibrate or sound at three different volumes Medtronic: YES: vibrate or sound at different volumes Dexcom: NO: Will first vibrate then sound at increasing volumes Pediatric issues Alarms

47. Solution: Improvise! On bedside table (in a glass) or under pillow on vibrate In hallway outside of room Baby monitor Sibling in the room! Spy equipment Paradigm Real-Time: More difficult because usually under blankets– new tech coming soon! Pediatric issues Overnight alarms Parent/child has difficulty hearing alarms at night PROBLEM : Parent/child has difficulty hearing alarms at night

48. Pediatric issues Calibrations GOAL: Be the BOSS of the Calibration: Only enter a calibration if BGs are STABLE SOLUTION: Calibrate before meals or 2 hours after food or insulin shot –Less likely to get a failed calibration alarm –More likely to get accurate sensor readings Calibration alarms annoying, inconvenient, and when fail, are frequent PROBLEM : Calibration alarms annoying, inconvenient, and when fail, are frequent

49. Family issues and dynamics Adaptation: “It is just part of our life now. I wear it all the time and don’t think much about it anymore.” 12 y.o. female Anxiety: “ I was worried that my mom was mad at my blood sugars all the time so I didn’t want to show her” 11 y.o. male Ambivalence: “I like it when it works but I worry it is going to fall out and I will have to put a new sensor in again” 14 y.o. male

50. Family issues and dynamics THE BOTTOM LINE: They have to live with diabetes, not with CGM Interval wear (example: 1 sensor/week) Occasional wear (example: during finals) Try again later

51. The future of CGM Smaller Longer sensor wears Less calibrations More insurance coverage Closed loop system (insulin pump responds to sensor glucose levels) Implantable sensors

52. Questions?