INTRODUCTION TO CONTINUOUS GLUCOSE MONITORS H. Peter Chase, MD Professor of Pediatrics Barbara Davis Center Aurora, CO Keystone Conference Wednesday, July 16, 2008 Barbara Davis Center for Childhood Diabetes May 2008

CGM Introduction Class The slides from our course for families interested in starting CGM are available for use in your centers. They are on our website: www.barbaradaviscenter.org. The slides can then be accessed by any of the following methods: 1. Click on the “CGM Slideset” tab 2. In the “Online Books and Teaching Slides” page: http://www.uchsc.edu/misc/diabetes/books.html 3. In the Clinical Resources section (last entry): http://www.uchsc.edu/misc/diabetes/school.html

What is a CGM? (Continuous Glucose Monitor) A device that provides “real-time” glucose readings and data about trends in glucose levels Reads the glucose levels under the skin every 1-5 minutes (10-15 minute delay) Provides alarms for high and low glucose levels and trend information The 3rd era in diabetes management Barbara Davis Center for Childhood Diabetes May 2008

Who Should Use a CGM?* The person and the family must both want a CGM A youth must be willing to wear the sensor (and carry the receiver) Using good diabetes care (4 BGs/day) Good support system Adequate body “real estate” Cost of CGM (RNs to elaborate) *(Understanding Pumps and CGMs, p.100) Barbara Davis Center for Childhood Diabetes May 2008

Continuous Glucose Monitoring (CGM) WHY? Prevention of low blood sugars (alarms) Prevention of high blood sugars (ketones) Minimize wide glucose fluctuations Behavior Modification Prevention of Complications (?) Barbara Davis Center for Childhood Diabetes May 2008

How common are glucose levels <60mg/dl during the night in children with T1D? French (i) and Australian (ii) data showed approximately 50% of children with low BG (<60mg/dl) during the night (on NPH bid) DirecNet data (one night in hospital with blood sugars every 30 min.) A) 2001-2002: 39 of 91 (43%) low BG (44% of children on insulin pumps/56% on NPH) B) 2004: 14 of 50 (28%) with low BG (all on insulin pumps or Lantus) Beregszaszi M, et al. J Pediatr. 131, 27, 1997 Porter PA, et al. J. Pediatr. 13, 366, 1997 Barbara Davis Center May 2008

Continuous Glucose Monitoring (CGM) WHY? Prevention of low blood sugars (alarms) Prevention of high blood sugars (ketones) Minimize wide glucose fluctuations Behavior Modification Prevention of Complications (?) Barbara Davis Center for Childhood Diabetes May 2008

“Snapshot of BG levels” Barbara Davis Center for Childhood Diabetes May 2008

Continuous Glucose Monitoring Barbara Davis Center for Childhood Diabetes May 2008

Hyperglycemia is common, especially after meals 50% > 300 40% 30% Breakfast Lunch 241 - 300 20% Dinner 181 - 240 10% < 180 0% Barbara Davis Center May 2008 Boland et al, Diabetes Care 24:1858, 2001

Continuous Glucose Monitoring (CGM) WHY? Prevention of low blood sugars (alarms) Prevention of high blood sugars (ketones) Minimize wide glucose fluctuations Behavior Modification Prevention of Complications? Barbara Davis Center for Childhood Diabetes May 2008

Three Parts to All CGMs:* Sensor Transmitter Receiver/Monitor *(Understanding Pumps and CGMs, p.103) Barbara Davis Center for Childhood Diabetes May 2008

Sensor (p.103) Barbara Davis Center for Childhood Diabetes May 2008

B)Transmitter (p.103) Barbara Davis Center for Childhood Diabetes May 2008

C)Receiver or Monitor (p.103) Barbara Davis Center for Childhood Diabetes May 2008

What does “Calibration” mean and why do I need to do it? Calibration is a process that gives a fingerstick BG value to the CGM system so the values will align with each other Number of Calibrations vary by device Best times to calibrate are when the BG values are stable: before meals and before bed Do not calibrate when arrows are present Barbara Davis Center for Childhood Diabetes May 2008

What type of data will we get? “Real-time” (Immediate) i. Trend graphs (p.109)* ii. Alarms (p.110)* iii. Trend arrows (p.113)* Barbara Davis Center May 2008 *(Understanding Pumps and CGMs)

i) TREND GRAPHS* Trend graphs – Knowing a glucose level is 240 mg/dl may not be as important as knowing the “trend.” *(Understanding Pumps and CGMs, p.103) Barbara Davis Center for Childhood Diabetes May 2008

ii) ALARMS (p.109) Can warn patients of current or projected high and low blood sugar Projected alarms: 10, 20, or 30 minute warning of impending hypo- or hyperglycemia (Navigator and Guardian devices) Threshold alarms: warning when glucose is below or above a set value (all devices) Barbara Davis Center for Childhood Diabetes May 2008

iii) TREND ARROWS (p.110) Rate of Change Arrows Gives the up-to-the-minute glucose value and a rate of change arrow Glucose rising quickly >2 (mg/dL)/min Glucose going up 1 to 2 (mg/dL)/min Fairly stable glucose -1 to 1 (mg/dL)/min Glucose going down -1 to -2 (mg/dL)/min Glucose falling quickly >-2 (mg/dL)/min Barbara Davis Center for Childhood Diabetes May 2008

Second type of data: (Retrospective, must download) Modal Day Graphs (p.113) Pie Chart (p.114) Statistics (p.113) *(Understanding Pumps and CGMs, Chapter 17, p.109) Barbara Davis Center for Childhood Diabetes May 2008

A) Case Study: Modal Day Graphs* Teenager with T1D for 9.5 years Started Navigator: Sept. 2005 Starting HbA1c: 7.1% Most recent HbA1c: 6.0% Current number of low BGs per week (<60 mg/dL or <3.3 mmol/L): 1/week Three “modal-day” graphs: *(Understanding Pumps and CGMs, p.113) Barbara Davis Center for Childhood Diabetes May 2008

A) BASELINE GLUCOSE MODAL DAY: i) Prior to Navigator Use Barbara Davis Center for Childhood Diabetes May 2008

A) GLUCOSE MODAL DAY Breakfast/Lunch Improvements ii) After three months of use Barbara Davis Center for Childhood Diabetes May 2008

A) GLUCOSE MODAL DAY iii) Most recent report Barbara Davis Center for Childhood Diabetes May 2008

B) PIE CHARTS (p.114) Barbara Davis Center for Childhood Diabetes May 2008

C) STATISTICS (p.113) Barbara Davis Center for Childhood Diabetes May 2008

(To “fine-tune” insulin and diabetes management) USE OF CGM RESULTS: (To “fine-tune” insulin and diabetes management) Important not to overwhelm families *** One change at a time *** Look for patterns 2 out of 3 days A behavior modification device  Missed boluses, snacking, low BGs on CGM iv) Good initial communication with HCP Barbara Davis Center for Childhood Diabetes May 2008

Questions? The presentation by the nurses will be next. You will then examine the CGMs from 3 companies. Barbara Davis Center for Childhood Diabetes May 2008

Part 2: CLINICAL STUDIES Use of CGM (The Navigator) in Clinical Studies of Children: A) Insulin Pump Study (JPediatr 151:388,2007) B) Lantus Study (DiabetesCare 31:525,2008)

CGM can help with glycemic control A) 30 Pump Patients Using Navigator x 13 weeks* N 30 Mean Age T1D duration 11.2 yr 5.8 years Female 40% HbA1c Initial 13 wks 7.1±0.6% 6.8±0.7% (p=0.02) *DirecNet J Pediatri 151,388,2007

* HbA1c HbA1c (%) § Baseline Week 7 Week 13 Week 26 Baseline A1c 7.0% 8.5 Baseline A1c 7.0% Baseline A1c >7.0% 8.0 N=15 7.5 * N=15 N=12 N=15 HbA1c (%) 7.0 N=13 § 6.5 N=15 N=15 N=13 6.0 5.5 Baseline Week 7 Week 13 Week 26 Black dots denote mean values and boxes denote median, 25th and 75th percentiles. * p=0.004 vs. baseline; § p=0.002 vs. wks 9-13.

Percentage of Navigator Glucose Values in Target Range 90% Baseline A1c 7.0% Baseline A1c >7.0% 80% 70% N=11 N=13 N=15 Percent in target range (71-180) 60% N=11 N=15 N=9 N=15 N=15 N=11 50% N=14 40% 30% Baseline Wks 1-4 Wks 5-8 Wks 9-13 Wks 14-17 Wks 18-21 Wks 22-26

Percentage of Navigator Glucose Values Below 70 mg/dL 14% Baseline A1c 7.0% 12% Baseline A1c >7.0% 10% 8% Percent below 70 mg/dL N=13 N=13 N=11 N=13 6% N=15 N=15 N=11 N=11 4% N=15 N=11 N=15 N=15 2% N=14 N=9 0% Baseline Wks 1-4 Wks 5-8 Wks 9-13 Wks 14-17 Wks 18-21 Wks 22-26

B) Lantus Subjects using CGM* 27 (23 completed) Age 11.0 ± 3.9 yr Female 14 (52%) Caucasian 25 (93%) HbA1c 7.9 ± 1.0% T1D duration 4.0 ± 3.1 yr MDI Regimen Glargine + RAIA* Glargine + RAIA* + NPH Other 21 (78%) 5 (16%) 1 ( 4%) * DirecNet: Diabetes Care 31:525, 2008

Lantus Subjects using CGM Results – Glycemic Control 9.5 Baseline A1c > 7.5% Baseline A1c ≤ 7.5% 9.0 8.5 * 8.0 HbA1c (%) 7.5 ** 7.0 6.5 6.0 ** p = 0.03 * p = 0.02 5.5 Baseline Week 7 Week 13

Lantus Subjects using CGM Results – Glycemic Variability 180 Baseline A1c > 7.5% Baseline A1c ≤ 7.5% 160 * 140 Mean Amplitude of Glycemic Excursion (MAGE, mg/dL) 120 ** 100 ** p = 0.17 * p = 0.004 80 Baseline Wks 1-4 Wks 5-8 Wks 9-13

Lantus Subjects using CGM Conclusions Use of the Navigator CGM was associated with an improvement in glycemic control without an accompanying rise in hypoglycemia Glycemic variability decreased with use of the Navigator Subjects and parents reported high overall satisfaction with the Navigator and did not demonstrate deterioration in quality of life during 3-month use CGM are tolerable and effective in children using MDI regimens

CGM Influences on Glucose Levels Blinded vs Non-Blinded CGM Tracings: p-value 21% less time <55 mg/dl <0.001 23% less time >240 mg/dl <0.001 26% more time in target <0.001 (81 – 140 mg/dl) (Garg et al, Diabetes Care 27:1922,2004)

COMMON MISCONCEPTIONS OF CGM (QUIZ) 1) “If I use CGM, I do not have to do BG checks anymore.” Barbara Davis Center for Childhood Diabetes May 2008

COMMON MISCONCEPTIONS OF CGM 2) “The starting of CGM will make diabetes management a breeze – so simple!” Barbara Davis Center for Childhood Diabetes May 2008

COMMON MISCONCEPTIONS OF CGM 3) “The use of CGM will fix the diabetes – all blood sugars will be perfect.” Barbara Davis Center for Childhood Diabetes May 2008

COMMON MISCONCEPTIONS OF CGM 4) “My CGM values should match my BG values.” Barbara Davis Center for Childhood Diabetes May 2008

COMMON MISCONCEPTIONS OF CGM 5) “The alarms will catch every low or pending low so I don’t need to worry about lows anymore.” Barbara Davis Center for Childhood Diabetes May 2008

CLOSED LOOP (BIONIC) PANCREAS “The Future” Will probably come in parts JDRF supporting algorithm development Should reduce glucose highs, lows, and fluctuations Will probably be more realistic than islet cell transplant FDA and medical insurance approvals (as with CGM) will be critical

Q. Why combine insulin pumps (CSII) and Continuous Glucose Monitors (CGM)? (p121) A: “They complement each other tremendously and provide the most ‘state of the art’ diabetes care available.” The CGM helps with: Cannulas dislodging Missed food boluses Hypoglycemia Corrections

Our Initial Data: Two oral presentations at ADA in June, 2008 (Abstract # 230-OR and 42-OR). Our emphasis: Preventing severe hypoglycemia at night. This may be the first part of a closed loop system acceptable to the FDA. We have shown that 80% of pending lows can be predicted. Safety remains the primary goal.

“Now let me get this right, Dr. Chase… You want the elves to make an artificial pancreas?” THANK YOU