2. Utilizing Insulin Pump Therapy in Challenging Populations Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia

3. ACE / AACE Targets for Glycemic Control A1C (HbA 1c ) < 6.5 % Fasting/preprandial glucose< 110 mg/dL Postprandial glucose< 140 mg/dL ACE / AACE Consensus Conference, Washington DC August 2001

4. RELATIVE RISK HbA 1c Skyler, Endo Met Cl N Am 1996 Relative Risk of Progression of Diabetic Complications by Mean A1C Based on DCCT Data

5. HbA1c and Plasma Glucose l 26,056 data points (A1c and 7-point glucose profiles) from the DCCT l Mean plasma glucose = (A1c x 35.6) – 77.3 l Post-lunch, pre-dinner, post-dinner, and bedtime correlated better with A1c than fasting, post-breakfast, or pre-lunch Rohlfing et al, Diabetes Care 25 (2) Feb 2002

6. Insulin The most powerful agent we have to control glucose

7. Patient J.L., December 15, 1922 February 15, 1923 The Miracle of Insulin

8. 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Plasma insulin Ideal Basal/Bolus Insulin Absorption Pattern

9. Glargine Plasma Glucose Time (hours) 220 200 180 160 140 120 12 11 10 9 8 7 04812162024 mg/dL mmol/L Lepore M, et al. Diabetes. 2000;49:2142–2148. n = 20 T1DM Mean ± SEM SC insulin NPH Ultralente CSII

10. Lauritzen. Diabetologia. 1983;24:326–329. Fast (n = 12) Semilente (n = 9) Intermediate (n = 36) Fraction at inj. site 1.00 0.75 0.50 0.25 0 6 121824 36 424830 Hours after single SC injections Femoral region Variability of Insulin Absorption CSII <2.8% Subcutaneous Injectable 10% to 52%

11. Pump Therapy Basal & Bolus Short-Acting Insulin

13. l Combined with SMBG, physiologic insulin requirements can be achieved more closely l Flexibility in lifestyle

14. History of Pumps

15. PARADIGM PUMP Paradigm. Simple. Easy.

16. Paradigm Pump: Advantages l 29% smaller, water resistant l Menu driven: bolus, suspend, basal, prime, utilities l Reservoir based (easier to fill) l Silent motor l AAA batteries

17. Paradigm Pump: Advantages l Various bolus options normal, square, dual, and “easy bolus” l Enhanced memory l Enhanced safety features (low reservoir alarm, auto off, etc.)

18. Pump Infusion Sets Softset QRSilhouette

19. Lauritzen. Diabetologia. 1983;24:326–329. Pharmacokinetic Advantages CSII vs MDI l Uses only regular or very rapid insulin –More predictable absorption than modified insulins (variation 3% vs 25 to 52%) l Uses 1 injection site –Reduces variations in absorption due to site rotation l Eliminates most of the subcutaneous insulin depot l Programmable delivery simulates normal pancreatic function

20. Metabolic Advantages with CSII l Improved glycemic control l Better pharmacokinetic delivery of insulin –Less hypoglycemia –Less insulin required l Improved quality of life

21. Case 1: DM 1 not at goal A1C l 35 year old female physician presents with Type 1 Diabetes since age 7 l Control suboptimal (A1C 8.7%) on MDI with Regular AC and NPH HS. l SMBG 5/day with CHO counting l Complications: mild retinopathy and neuropathy, and hypoglycemia induced migraines

22. Case 1: DM 1 not at goal A1C l Recommend CSII but refuses; Does not want to be attached to something l Ask her to record, monitor 6 to 7 times per day, fax readings, and try lispro l She complies with minimal change in A1C falling to 8.4% at 3 months and 7.7% at 6 months l Still refuses CSII l Recommend a sensor (CGMS)

23. Case 1: DM 1 not at goal A1C l CGMS confirms a dawn rise l Try giving NPH later but no help; Try lente and ultralente but no help; Glargine only available in Germany l Patient gets married and desires children l Attempt to get Glargine from Germany but my contacts say no one uses glargine in pregnancy. Put her on a pump

24. Case 1: DM 1 Agrees to CSII

25. l Patient loves the pump l No more migraines from hypoglycemia l Patient now 13 weeks pregnant with A1C at 5.7%

26. CSII Reduces HbA 1c 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5.09 9.5 10.0 n = 58n = 107n = 116n = 50n = 25n = 56 Mean dur. = 36 Adolescents Adults Mean dur. = 36Mean dur. = 54Mean dur. = 42Mean dur. = 12 Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327; Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Bell DSH, et al. Endocrine Practice. 2000;6:357–360; Chase HP, et al. Pediatrics. 2001;107:351–356. BellRudolphChanteleauBodeBolandChase Pre-pumpPost-pump HbA 1c

27. CSII Reduces Hypoglycemia 0 20 40 60 80 100 120 140 160 n = 55 Mean age 42 n = 107 Mean age 36 n = 116 Mean age 29 n = 25 Mean age 14 n = 56 Mean age 17 Events per hundred patient years Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327; Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Chase HP, et al. Pediatrics. 2001;107:351–356. BodeRudolphChanteleauBoland Chase Pre-pumpPost-pump

28. l Monitoring –HbA 1c = 8.3 - (0.21 x BG per day) l Recording 7.4 vs 7.8 l Diet practiced –CHO: 7.2 –Fixed: 7.5 –Other: 8.0 CSII Factors Affecting HbA 1c Bode et al, Diabetes 1997;46:143

29. Case 2: New Onset Diabetes l 45 year old male lawyer presents with polys and weight loss l Sees internist who recommends metformin (blood glucose 500, urine ketones small, BMI 26) l The lawyer does some internet reading and seeks a second opinion from diabetes specialist who was a high school classmate he has not seen for 27 years

30. Case 2: New Onset Diabetes l Sees myself the following am (BG 514, urine ketones small) l I concur with him he has Type 1 Diabetes and metformin is not the treatment, insulin is. l He asks about insulin pump therapy instead of multiple injections. l I hospitalized him and told him I would get back to him the following am.

31. Case 2: New Onset Diabetes l I see him in the am and tell him that 8 out of 10 CSII patients polled yesterday would have started CSII at onset if offered the choice. l Dr. Pozzilli, an expert in DM 1 prevention, also recommended CSII at onset if it was him or a close relative l Patient opted for CSII

32. Case 2: New Onset Diabetes on CSII: A1C Results

33. Case 2: New Onset Diabetes on CSII l Patient extremely satisfied with his care l C-peptide 0.9 to 0.8 at 1 year l Does not understand why everyone is not on CSII with optimal control

34. Case 3: DM 2 Poorly Controlled l 58 year old female presented with a 12 year history of poorly controlled, insulin treated diabetes l Ht 66’’, Wt 174#, BMI 28, C-peptide 2.1 l A1C 10.4% on 165 units per day (70/30 BID) l Added troglitazone, metformin, glimepiride to MDI insulin l A1C range 7.7 to 12.6% over 3 years

35. Case 3: DM 2 Poorly Controlled l Admitted twice for IV insulin and fasting with short lived success (A1C to 7.6% but back up to 12.6%) l Tried weight watchers and appetite suppressants; no help l Decided to try CSII

36. Case 3: DM 2 on CSII, A1C Results

37. Case 3: DM 2 Poorly Controlled l Patient loves the pump l On 110 units per day consuming 2 meals only per day (1.4 units per kg or 0.6 units per lbs) l Also on rosiglitazone 4 mg/day

38. 7.19 7.57 9.2 5.00 6.00 7.00 8.00 9.00 10.00 Baseline6 months18 months P = 0.026P = 0.040 N = 11 CSII Usage in Type 2 Patients Atlanta Diabetes Experience Mean HbA 1c (%) Davidson et al, Diabetologia 1999; 42: 796

39. Glycemic Control in Type 2 DM: CSII vs MDI in 127 patients l A1C 7.0 7.2 7.4 7.6 7.8 8.0 8.2 8.4 CSIIMDI Baseline End of Study (24 wks) Raskin, Diabetes 2001; 50(S2):A106

40. DM 2 Study: CSII vs MDI l Overall treatment satisfaction improved in the CSII group: 59% pre to 79% at 24 weeks l 93% in the CSII group preferred the pump to their prior regiment (insulin +/- OHA) l CSII group had less hyperglycemic episodes (3 subjects, 6 episodes vs. 11 subjects, 26 episodes in the MDI group) p<0.01

41. Normalization of Lifestyle l Liberalization of diet — timing & amount l Increased control with exercise l Able to work shifts & through lunch l Less hassle with travel — time zones l Weight control l Less anxiety in trying to keep on schedule

42. N = 165 Average Duration = 3.6 years Average Discontinuation <1%/yr Continued 97% Discontinued 3% Current Continuation Rate Continuous Subcutaneous Insulin Infusion (CSII) Bode BW, et al. Diabetes. 1998;47(suppl 1):392.

43. U.S. Pump Usage Total Patients Using Insulin Pumps

44. Pump Therapy Indications l HbA 1c >6.5% l Frequent hypoglycemia l Dawn phenomenon l Exercise l Pediatrics l Pregnancy l Gastroparesis l Hectic lifestyle l Shift work l Type 2 Marcus. Postgrad Med. 1995.

45. Current Candidate Selection Patient Requirements –Willing to monitor and record BG –Motivated to take insulin –Willing to quantify food intake –Willing to follow-up

46. Meal bolus 1 2 3 4 5 6 12 am12 pm12 am Time of day Basal rate Pump Therapy Units Meal boluses l Insulin needed pre-meal – Pre-meal BG – Carbohydrates in meal – Activity level l Correction bolus for high BG Basal rate l Continuous flow of insulin l Takes the place of NPH or glargine insulin

47. If A1C Not to Goal l SMBG frequency and recording l Diet practiced –Do they know what they are eating? –Do they bolus for all food and snacks? l l Infusion site areas –Are they in areas of lipohypertrophy? l l Other factors: –Fear of low BG –Overtreatment of low BG Must look at:

48. If A1C Not to Goal and No Reason Identified l Place on a continuous glucose monitoring system (CGMS) to determine the cause

49. Summary l Insulin pump therapy offers improvement in glycemic control with less major hypoglycemia and greater flexibility in lifestyle l Insulin pump therapy should be considered in all DM 1 patients and DM 2 patients failing conventional insulin therapy (basal insulin)

50. QUESTIONS l For a copy or viewing of these slides, contact l WWW.adaendo.com WWW.adaendo.com