1. P UMPMASTER AND G LUCOMMANDER THE FAR SIDE OF THE DIABETES WORLD Presented by Paul Davidson MD at the MiniMed Symposium Atlanta, GA December 13, 2003

2. AIM Formulae (Accurate Insulin Management) Background l CSII dosing is related to a patient’s size l It consists of four parameters: –Total insulin dose per day (TDD) –Basal Insulin as percent of TDD –Bolus insulin for meals Based on CHO to insulin ratio (CIR) –Correction boluses from the correction factor (CF) l A database of 1815 records was used to find the optimal parameters for the most ideally controlled pump patients. l The interaction of the AIM formulae is portrayed as a nomogram.

3. Materials and Methods Two groups of patients: –Target Group (TG)--183 patients with A1C <7% –Not-to-Target Group (NTG) the remainder of the patients –Individual's slopes determined: Basal versus TDD CF versus 1/TDD –Median of all slopes in the TG was used as the slope for each formula –Slignificant differences between TG and NTG. TDD versus BW CIR versus BW/TDD

4. AIM Formulae for adults Carbohydrate / Insulin Ratio (CIR) CIR = 2.8 x BodyWeight(lbs) / TDD Correction Factor (CF) CF = 1700 / TDD Basal Insulin Basal = 0.48 x TDD

5. Starting Total Daily Insulin Dose TDDstart = 0.24 * Wt(lb) n = 199 File: AIM031208 199 points

6. Basal Insulin Basal = 0.48 * TDD n = 199 File: AIM031208 199 points

7. If HbA 1c is Not to Goal i.e. 6.5% l SMBG –frequency –recording –memory meter l Diet –accurate CHO counting –appropriate CHO/insulin bolusing l l Infusion site areas l l Over-treatment of low BG l l Delayed or under-treatment of high BG

8. If HbA 1c Not to Goal i.e. 6.5% l SMBG –frequency –recording –memory meter l l Infusion site areas l l Over-treatment of low BG l l Delayed or under-treatment of high BG More than 4/day 2.8 x Wt / TDD 1700 Rule (100-BG) x 0.2 lDiet –accurate CHO counting –appropriate CHO/insulin bolusing

9. Average 2 BG’s/d Average 12 BG’s/d 24 Blood Glucose Hours Frequency of Blood Glucose Monitoring Effect of Recurrent Adjustment for Increased BG’s

10. Improvement in HbA 1c with Increased BG Testing

11. If HbA 1c Not to Goal i.e. 6.5% l SMBG –frequency –recording –memory meter l l Infusion site areas l l Over-treatment of low BG l l Delayed or under-treatment of high BG More than 4/day 2.8 x Wt / TDD 1700 Rule (100-BG) x 0.2 lDiet –accurate CHO counting –appropriate CHO/insulin bolusing

12. 450 Rule vs 2.8 Rule Purpose of rule: Estimate the ratio: carbs / insulin. Start with: CIR = CarbsPerDay / TDD 2.8 Rule : says CarbsPerDay proportional to Wt(lb): CIR = 2.8 * Wt(lb) / TDD 450 Rule : says CarbsPerDay is the same for all people: CIR = 450 / TDD The case for 450 rule: Advocates say it works better for children. The case for 2.8 Rule: Wt(lb) for CarbsPerDay makes better sense than constant. Consistent with 1700 Rule 450 Rule’s scatter chart data look curved. A future study is planned for children. They were under-represented in AIM study.

13. Median slope = 2.79 Data: file: AIM031208.xls, 179 pts CARBOHYDRATE TO INSULIN RATIO CIR = 2.8 * BW# / TDD for adults

14. Median slope = 450 Data: file: AIM031208.xls, 179 pts CARBOHYDRATE TO INSULIN RATIO CIR = 450 / TDD

15. If HbA 1c Not to Goal i.e. 6.5% l SMBG –frequency –recording –memory meter l l Infusion site areas l l Over-treatment of low BG l l Delayed or under-treatment of high BG More than 4/day 2.8 x Wt / TDD 1700 Rule (100-BG) x 0.2 lDiet –accurate CHO counting –appropriate CHO/insulin bolusing

16. Correction of Hypoglycemia with Glucose 100-BG X 0.2 Grams BeforeAfter Richardson Diabetes 1999 50:A200 100-BG X 0.15 Grams

17. If HbA 1c Not to Goal i.e. 6.5% l SMBG –frequency –recording –memory meter l l Infusion site areas l l Over-treatment of low BG l l Delayed or under-treatment of high BG More than 4/day 2.8 x Wt / TDD 1700 Rule (100-BG) x 0.2 lDiet –accurate CHO counting –appropriate CHO/insulin bolusing

18. Correction Factor The 1700 Rule CF = 1705 / TDD n = 199 File: AIM031208 199 points

19. 1700 Rule Mathematical Model Purpose of 1700 Rule: Estimate Correction Factor (CF) 1700 Rule: says glucose burned per day and body volume are both proportional to Wt(lb). These cancel as shown below: CF = (glucose burned per day)/[(Body volume)*TDD] CF = K1 * Wt(lb) / [ Wt(lb) * TDD] CF = K1 / TDD Statistics give: CF = 1700 / TDD

20. 125 100 75 50 25 Correction Factor 25 20 15 12 10 8 7 6 5 Carbohydrate to Insulin Ratio CF Curve AIM Nomogram ( CIR = 2.8 Wt / TDD ) ( CF = 1700 / TDD ) Initial Dosing: Plot BW and 25 CIR for BI Plot BW and 12 CIR for TDD Plot BW and TDD for CIR Plot TDD and CF curve for CF 4 3 2

21. 125 100 75 50 25 Correction Factor 25 20 15 12 10 8 7 6 5 Carbohydrate to Insulin Ratio CF Curve ( CIR = 2.8 Wt / TDD ) ( CF = 1700 / TDD ) 4 3 2 CIR TDD BI Weight Example 210 lb.. Man Type 1 Diabetes Starting CSII Poorly controlled HgA1c 8.1% 10 units lispro tid 28 units glargine hs Initial Dosing: Plot BW and 25 CIR for BI Plot BW and 12 CIR for TDD

22. 125 100 75 50 25 Correction Factor 25 20 15 12 10 8 7 6 5 Carbohydrate to Insulin Ratio CF Curve ( CIR = 2.8 Wt / TDD ) ( CF = 1700 / TDD ) 4 3 2 CF TDD Plot TDD and CF curve for CF

23. 125 100 75 50 25 Correction Factor 25 20 15 12 10 8 7 6 5 Carbohydrate to Insulin Ratio CF Curve ( CIR = 2.8 Wt / TDD ) ( CF = 1700 / TDD ) 4 3 2 New TDD New CIR New BI Follow-up One Month Later Weight 200# 4.5 BG’s per day Average BG 172 Current basal 1.2 u/hr (28.8 u/d) TDD from pump 64 units New CF New Weight

24. AIM “N” Nomogram

25. Total CIR Daily Wt Wt for adults Insulin CF (kg) (lb) (gm/unit) (unit) (mg/dL/unit) 149 ┼ 329 ┼ 47 20 ┼ 88 142 ┼ 313 ┼ 43 21 ┼ 84 135 ┼ 298 ┼ 39 22 ┼ 80 129 ┼ 284 ┼ 35 23 ┼ 76 123 ┼ 270 ┼ 32 24 ┼ 72 117 ┼ 258 ┼ 29 25 ┼ 69 111 ┼ 245 ┼ 26 26 ┼ 65 106 ┼ 234 ┼ 24 28 ┼ 62 101 ┼ 222 ┼ 22 29 ┼ 59 96 ┼ 212 ┼ 20 30 ┼ 57 92 ┼ 202 ┼ 18 32 ┼ 54 87 ┼ 192 ┼ 16 33 ┼ 51 83 ┼ 183 ┼ 15 35 ┼ 49 79 ┼ 174 ┼ 13 37 ┼ 47 75 ┼ 166 ┼ 12 39 ┼ 44 72 ┼ 158 ┼ 11 41 ┼ 42 68 ┼ 151 ┼ 10 43 ┼ 40 65 ┼ 143 ┼ 9 45 ┼ 38 62 ┼ 137 ┼ 8 47 ┼ 36 59 ┼ 130 ┼ 7 49 ┼ 35 56 ┼ 124 ┼ 7 52 ┼ 33 54 ┼ 118 ┼ 6 55 ┼ 31 51 ┼ 112 ┼ 5 57 ┼ 30 49 ┼ 107 ┼ 5 60 ┼ 29 46 ┼ 102 ┼ 5 63 ┼ 27 44 ┼ 97 ┼ 4 66 ┼ 26 42 ┼ 92 ┼ 4 70 ┼ 25 40 ┼ 88 ┼ 3 73 ┼ 23 38 ┼ 84 ┼ 3 77 ┼ 22 36 ┼ 80 ┼ 3 81 ┼ 21 35 ┼ 76 ┼ 3 85 ┼ 20 33 ┼ 72 ┼ 2 89 ┼ 19 31 ┼ 69 ┼ 2 93 ┼ 18 30 ┼ 66 ┼ 2 98 ┼ 18 28 ┼ 63 ┼ 2 103 ┼ 17 27 ┼ 60 ┼ 2 108 ┼ 16 26 ┼ 57 ┼ 1 113 ┼ 15 25 ┼ 54 ┼ 1 119 ┼ 14 23 ┼ 51 ┼ 1 125 ┼ 14 Accurate Insulin Management (AIM) Nomogram 1.Connect the columns with a straight line between weight and total daily dose of insulin (TDD). 2.Read correction factor (CF) and carbohydrate/insulin ratio (CIR). 3.Basal insulin is one-half total daily dose of insulin.

26. AIM Study (uncontrolled) l 21 Patients l HbA1c>8 l Competent Self- Monitoring l Pump Veterans l Bi-Weekly Fax and Phone Follow-Up l Three Month Study Davidson et al Diabetes Technology & Therapeutics 2003 180 160 140 120 P<0.0001

27. PumpMaster A Combined Database Collector and Patient-Treatment Advisor for Interactive Use by Practitioners

28. Pumpmaster l Day divided into five periods –Sleep, dawn, am, pm, evening l BG monitored initially for each period –Mean and SD l Variation of mean from target –Correction formula used to quantify average insulin need for each period –Summed for day l Program suggests change in insulin for each period balancing change in basal against CIR –Simulates best controlled patients in database

29. Input Form, Screen 1

30. Input Form, Screen 2

31. In development (Patent Pending) Has shown that it lowers A1c Will advise the pump therapist Will advise the pump-wearing diabetic Will encourage more pump prescribing Will facilitate progress to target control Can be programmed into PDA or pump Overview of PumpMaster

32. Future of Diabetes Management Improvements in Insulin & Delivery l Insulin analogs and inhaled insulin l Smart external pumps l Internal pumps l Real-time sensors l Closed-loop systems l Unconceived-of solutions

33. QUESTIONS? l For a copy or viewing of these slides –Contact www.adaendo.com l How can I get use of Glucommander? (Computer-directed IV insulin program) – Available for review on internet, www.glucommander.com l How can I get use of Pumpmaster? – Contact us expressing interest: Pumpmaster@adaendo.com