1. Suggestions on Diabetes Care What Parents Should Know Jeff Hitchcock Children with Diabetes January 2007

2. www.childrenwithdiabetes.com Goals for Today Overview of current tools and techniques Its more than type 1 diabetes Some science Hints at the future Mostly, reassurance

3. www.childrenwithdiabetes.com Knowledge is … "...you shall know the truth, and the truth shall make you free." John 8:32 Power Life: The diabetic who knows the most lives the longest. -- Elliott Joslin

4. www.childrenwithdiabetes.com Tools … or Diabetes Technology Glucose Meters Other Meters LancingWhere the metal meets the skin Insulin delivery Other drugs Continuous sensors

5. www.childrenwithdiabetes.com What to Look for in a Glucose Meter Accuracy –Major brands make a difference –But technique matters Memory with PC download –Pattern analysis to reduce variability Intangibles –Lighting –Ease of use –On board data analysis

6. www.childrenwithdiabetes.com FreeStyle Flash Smallest meter 0.3 microliter sample 7+ second test time 250 test memory 14 day average 4 built in alarms for test reminders Built in backlight and test strip light Interfaces with a PC Most popular at CWD: 21% Last poll: http://www.childrenwithdiabetes.com/poll/poll20061001.htm

7. www.childrenwithdiabetes.com ACCU-CHEK Compact Plus 17-test strip drum 1.5 microliter blood volume 5 second test time One handed testing Could attach to car dashboard and check while driving

8. www.childrenwithdiabetes.com OneTouch UltraSmart On board analysis and graphing 1 microliter sample 5 second test time 3,000 test memory Tracks glucose, insulin, food, and exercise Interfaces with a PC Clinical trial shows use can lower A1c

9. www.childrenwithdiabetes.com GlucoMON How do I know my child checked at … ? Wireless interface to a OneTouch Ultra Remote oversight of glucose testing Available in limited markets in the US

10. www.childrenwithdiabetes.com Other Meters: Ketone Testing Old Way: Urine –Yucky –15 seconds –As low as 10¢ per test –Accuracy issues –Force a child to pee? New Way: Blood –Familiar, easy –10 seconds –1.5 microliters –About $4 per test –Clinical benefits Diabetic Medicine 23 (3), 278-284

11. www.childrenwithdiabetes.com Other Meters: A1c Measurement Old way: venous blood draw, results long after the clinic visit Can be very stressful, sometimes painful In 1999, study showed that discussing A1c at clinic visit improved control Enter the DCA2000 and A1cNow+ Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin- treated type 2 diabetic patients (Diabetes Care. 1999 Nov;22(11):1785-9) New A1cNow+ has variance of around 3% and a blood volume of 5 microliters. About $10 per test. Available early 2007 for home use. DCA2000 is for office use. Finger stick sample, results in minutes.

12. www.childrenwithdiabetes.com Lancing Lancing is often overlooked, yet its a major reason people dont check because it hurts Many people rarely change lancets –25% report changing only when painful or bounces MultiClix is the best lancing device for kids –No exposed sharp ever –6 lancets on board –Very easy to use

13. www.childrenwithdiabetes.com Insulin Delivery – Some Science 65% of kids on pumps missed more than 1 meal bolus/week 2 missed meal bolus/week caused A1c to increase ½% Insulins a great drug if you take it -- Dr. Darrell Wilson, Stanford Burdick, Chase, Pediatrics 113: e221, 2004

14. www.childrenwithdiabetes.com Insulin Delivery – Injection Devices Pens and pen-like devices becoming more common in the US; the norm elsewhere Dosing convenience the issue Allows for very precise dosing that cannot be matched with syringes Downside is no mixing

15. www.childrenwithdiabetes.com Insulin Delivery – Insulin Pumps Studies show better A1c with lower risk of hypoglycemia, especially in grade school kids Studies show efficacy even in infants Untethered Regimen allows for pump breaks Pumps not shown to scale

16. www.childrenwithdiabetes.com SymlinAnother Drug Slows gastric emptying Suppresses postprandial glucagon secretion Makes you feel full sooner Can help you lose weight But … –Nausea at first –Must decrease insulin because of delayed absorption of food –Severe lows if not attentive Use in <18 off label

17. www.childrenwithdiabetes.com Diabetes Mixology Lantus –No change in A1c when mixed and immediately injected Glucagon –Glucagon is effective for at least 7 days once mixed and stored at room temperature Symlin –Anecdotal evidence shows no difference via syringe –Some reports of mixing in pumps This is all very off label J Pediatr. 2006 Apr;148(4):481-4

18. www.childrenwithdiabetes.com Continuous Glucose Sensors Promises a revolution in diabetes care Minute-by-minute glucose data has dramatic clinical implications Predictive alarming for impending lows and highs Future: Sensor + Pump = Closed Loop? MiniMed Paradigm® REAL-Time System DexCom STS® Abbott Freestyle Navigator

19. www.childrenwithdiabetes.com Pumps and Sensors Integrated display Separate probes No control

20. www.childrenwithdiabetes.com Its Not About Blood Anymore Continuous sensors look at interstitial fluid, not blood Blood has been easy to access, but … … interstitial might be the better compartment We really care about the brain, not the fingertip Danish pot belly pig study

21. www.childrenwithdiabetes.com CGMS Performance From Use of Continuous Glucose Monitoring in the Detection and Prevention of Hypoglycemia by Howard A. Wolpert, M.D. (J Diabetes Sci Technol 2007; 1:146-150). Original from Evaluating the Clinical Accuracy of Two Continuous Glucose Sensors Using Continuous Glucose–Error Grid Analysis by William Clarke, et al (Diabetes Care 2005 28: 2412-2417) Performance of the two sensors during induced moderate hypoglycemia.

22. www.childrenwithdiabetes.com CGMS Accuracy % MAD of HGM 1989-1996 Diabetes Care 26:1176, 2003 From Bruce Buckingham, CWD FFL 2005

23. www.childrenwithdiabetes.com Navigator Accuracy CONCLUSIONS The Navigators accuracy does not yet approach the current generation home glucose meters, but it is sufficient to believe that the device has the potential to be an important adjunct to treatment of youth with type 1 diabetes.

24. www.childrenwithdiabetes.com More than DiabetesCeliac Allergy to gluten (wheat, barley, rye) Autoimmune disease About 10% of people with type 1 have celiac Can explain erratic control Testing is easy … … Living with getting easier

25. www.childrenwithdiabetes.com The Effects of Celiac Left: Healthy villi – increases the absorption area of the intestinal mucosa to ~ 250 square yards Right: Villi that have been destroyed by celiac antibodies – absorption area just ~ 2 square yards From Ragnar Hanas, CWD FFL 2006

26. www.childrenwithdiabetes.com Some Science– Risk for Retinopathy 0 1 2 3 4 5 6 7 8 9 24201612840 Conventional Adapted from Diabetes 44:968-983, 1995 From Irl Hirsch, DTM 2006 11% Rate Per Patient Year 10% 9% 8% 7% Time During Study (Years) Mean HbA1c 0 1 2 3 4 5 6 7 8 9 Intensive Rate Per Patient Year 9% 8% 7% Time During Study (Years) 24201612840 Mean HbA1c Tight Control Matters More Than We Thought

27. www.childrenwithdiabetes.com Could it be Glucose Variability? Cell death of human umbilical vein endothelial cells Variability in glycemic control may be more deleterious than a constant high concentration of glucose Am J Physiol Endocrinol Metab 281: E924-E930, 2001 From Irl Hirsch DTM2006

28. www.childrenwithdiabetes.com OK, So Give Me a Goal What makes this hard to achieve? –Not taking enough insulin (check fasting) –Miscounting carbs (under or over bolusing) –Gastroparesis or celiac –Not pre-bolusing or missing meal boluses –Erratic snacking and not covering with insulin –Absorption variability Youre not still using NPH are you? SD X 2 < MEAN From Irl Hirsch DTM2006

29. www.childrenwithdiabetes.com Hints at the FutureClosing the Loop Sensor + Pump = Set it and forget it? Semi closed loop –Pre-meal bolus, or at least partial pre-meal bolus –Even semi closed loop can provide essentially normal blood sugars for at least 1/3 rd of the day – at night Fully closed loop –Set it and forget it –Sensor lag (?) and kinetics of insulin action remain a major challenge Is glucagon also needed? –At recent Diabetes Technology Meeting, 60% of attendees decided yes after one presentation (vs. 47% pre)

30. www.childrenwithdiabetes.com Why Even Semi-Closed Loop Matters Artificial External Insulin Pump GARRY M. STEIL, Diabetes 53:A3, 2004 SLEEP!

31. www.childrenwithdiabetes.com Sensor glucose levels during CL control vs. home open-loop pump therapy From Stu Weinzimer, DTM 2006

32. www.childrenwithdiabetes.com Comparing Closed vs. Semi Closed Loop: Single Meal Example From Stu Weinzimer, DTM 2006

33. www.childrenwithdiabetes.com Reference Glucose Levels in Closed Loop Versus Hybrid (Semi Closed) MeanDaytimePeak PP Full CL 149 57160 59226 51 Hybrid 140 46149 47197 47 From Stu Weinzimer, DTM 2006

34. www.childrenwithdiabetes.com In Closing … The tools are good and getting better Pump therapy has decided advantages Dont be afraid to mix More data means better decision making –Continuous sensing is real Variability might be as important as A1c Get checked for celiac