1. Basal-Bolus, Insulin Pumps, Carbohydrate Counting, Combination Therapy Dr.Ihab Tadros Medical Director Daisy Care Medical – USA The Leader in insulin Pump Therapy

2. Educational Objectives  At the completion of this presentation the attendee will be able to: Describe the principles behind physiologic basal-bolus insulin therapy. Recite the principles and the indications for CSII (Insulin pump therapy) in the management of diabetes. Apply the concepts of counting grams for appropriate insulin therapy and review the Quick-Carb Count system for determining carbohydrate grams. Discuss the principles and appropriate indications for combination therapy.

3. 4:00 25 50 75 8:0012:0016:0020:0024:00 4:00 BreakfastLunchDinner Plasma Insulin µ U/ml) Physiological Insulin Secretion Profile Time

4. Comparative Action of Insulins OnsetPeakDuration Lispro5-15 min0.5-1.5 hr5 hr Aspart5-15 min0.5-1.5 hr5 hr Glulisine5-15 min0.5-1.5 hr5 hr Regular30-60 min2-3 hr6-8 hr NPH2-4 hr4-10 hr10-16 hr Glargine2-4 hrNone20-24 hr Detemir2-4 hrNone12-24 hr

5. Profiles of Human Insulins and Analogs 0 2468 10 12141618202224 Plasma insulin levels Regular (6–8 h) NPH (10–16 h) Hours Detemir, Glargine (20-24 h) Aspart, Glulisine, Lispro (4–5 h)

6. Insulins That Most Closely Match the Physiologic Insulin Profile  Bolus (prandial) insulin analogs Rapid acting When taken ten minutes before eating, most closely coincides with CHO absorption rate  Basal (background) insulin analogs Long-acting Slow and steady rate of absorption

7. 4:00 25 50 75 16:0020:0024:004:00 BreakfastLunchDinner Plasma Insulin µ U/ml) Ideal Insulin Replacement Pattern 12:008:00 Time

8. Augmentation of the Beta-Cell  Exogenous insulin administered to augment endogenous production  Often required at about 6 years post diagnosis  Glucose rises in spite of treatment with oral antidiabetic drug(s)

9. Mr. Brown  52 yo CM with T2DM for 7 years  Treated with SU, metformin, lifestyle changes Has lost 28 pounds since diagnosis Walks 30-45 minutes 5-6 days per week  Last A1C has increased from 7.2% to 9.3% and HGM has indicated rising values

10. ARS Question #1  What do you recommend? 1. Do you add another oral agent? 2. Do you consider an alternative agent? 3. Do you consider insulin?

11. Mr. Brown  Insulin therapy has the best chance of achieving target A1C  The natural history indicates that insulin is needed  Other agents work in the presence of adequate insulin—endogenous plus exogenous

12. Mr. Brown  Choices for beginning insulin Basal insulin each evening  Insulin detemir (Levemir)  Insulin glargine (Lantus)  NPH Combination (rapid-acting/ intermediate acting) insulin before evening meal  Insulin protaminated aspart/ aspart (NovoLog 70/30)  Insulin protaminated lispro/lispro (Humalog 75/25)

13. 4:0016:0020:0024:004:00 BreakfastLunchDinner 12:008:00 Time Detemir, Glargine Plasma Insulin Basal Insulin Bedtime Only

14. Analog Mixed Insulin Program 4:0016:0020:0024:004:00 BreakfastLunchDinner 12:00 Time Plasma Insulin 8:00

15. ARS Question #2  How do you begin insulin therapy? 1. Insulin detemir 0.1-0.2 units/kg or 10-20 units each evening 2. Insulin glargine 0.1-0.2 units/kg or 10-20 units each evening 3. Insulin protaminated aspart/aspart (NovoLog Mix 70/30) 12 units before evening meal 4. Any of the above

16. 24-Hour Plasma Glucose Curve Normal and Type 2 Diabetes Time of Day 400 300 200 100 0 0600 10001400180022000200 NEJM 318: 1231-1239, 1988 Glucose (mg/dL) Diabetes Normal

17. ARS Question #3  What do you do with the existing oral agents? 1. Continue the SU and metformin 2. Continue the SU but not metformin 3. Continue metformin but not the SU 4. Discontinue the SU and metformin

18. Mrs. Blue  59 yo AAF with T2DM for 13 years Currently treated with SU, MF, and insulin detemir once each evening  Recently her A1C has increased from 7.4% to 8.5%

19. ARS Question #4  What do you now recommend? 1. Continue SU and metformin; give insulin detemir twice daily 2. Discontinue SU and metformin; give insulin detemir twice daily 3. Discontinue SU, add bolus insulin before largest meal (dinner) 4. Discontinue SU, add bolus insulin before breakfast and dinner 5. None of the above

20. Diabetes 44: 1249-1258, 1995 UKPDS: β-Cell Function over 6 Years Years After Diagnosis -Cell Function (% ) N=376 51% residual secretion 28% residual insulin secretion Decline to insulin deficiency ~ 12 yrs after Dx! Insulin loss starts 10 yrs before Dx. Half gone by Dx. Insulin loss is part of T2 DM 10/22/02

21. Replacement Insulin Therapy  Beta cells are now producing very little insulin  She requires a physiologic insulin replacement regimen Basal-bolus system Similar to a patient with T1DM

22. 4:00 25 50 75 8:0012:0016:0020:0024:00 4:00 BreakfastLunchDinner Plasma Insulin µ U/ml) Physiological Insulin Secretion Profile Time

23. Mrs. Blue  Insulin choices Basal  Insulin detemir  Insulin glargine Bolus  Insulin aspart  Insulin lispro  Insulin glulisine

24. 4:00 25 50 75 16:0020:0024:004:00 BreakfastLunchDinner Plasma Insulin µ U/ml) Ideal Insulin Replacement Pattern 12:008:00 Time

25. As Patients Get Closer to A1C Goal, the Need to Manage PPG Significantly Increases Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Diabetes Care. 2003;26:881-885. Increasing Contribution of PPG as A1C Improves % Contribution 0 20 40 60 80 100 A1C Range (%)

26. 4:0016:0020:0024:004:00 BreakfastLunchDinner 12:008:00 Time Detemir/ Glargine Basal + Meal-Related Regimen Plasma Insulin Aspart Aspart, Aspart, Lispro Lispro, Lispro, Glulisine Glulisine Glulisine

27. 4:0016:0020:0024:004:00 BreakfastLunchDinner 12:00 Time Plasma Insulin 8:00 Basal Insulin: Twice Daily - AM & Bedtime Detemir/ Glargine

28. Mrs. Blue  In a person with T2DM Total daily insulin dose = 1.0 -1.2 units/ kg Divide total daily dose  50% basal insulin (insulin detemir, glargine)  Give each evening and adjust based on the fasting glucose  50% bolus insulin (insulin aspart, glulisine, lispro)  Give pre-meal and adjust based on the next pre-meal glucose or ideally 2 hours post-meal  Goal: 2 h post-meal = pre-meal +/- 40 mg/dL

29. Mrs. Blue  Most patients will require more insulin on board in the AM (physiologic basis) Start with bolus dose divided pre-meal 1/3, 1/3, 1/3  Adjust based on post-prandial blood glucose Most patients require:  38% of total bolus dose pre-breakfast  28% of total bolus dose pre-lunch  33% of total bolus dose pre-dinner

30. ARS Question #5  What to do with the oral agents? 1. Discontinue the SU and metformin 2. Discontinue the SU, continue metformin 3. Discontinue metformin, continue the SU 4. Continue the SU and metformin

31. Mrs. Blue 1. Discontinue the SU Very little beta-cell reserve No reason to give an agent to stimulate phase 2 insulin release 2. Continue metformin Improve insulin resistance Lowers total insulin requirement Limits potential weight gain

32. Continuous Subcutaneous Insulin Infusion (CSII): Insulin Pump Therapy  Principles Allows reproduction of an intact endogenous system of insulin release Allows variation in the basal infusion rate during the 24-hour period Allows an immediate insulin bolus with carbohydrate intake Allows temporary suspension (cessation) of insulin infusion

33. 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Basal infusion Bolus Plasma insulin Variable Basal Rate: CSII Program

34. Indications for CSII  Elevated A1C  Hypoglycemia  Exercise  Dawn phenomenon  Pregnancy  Gastroparesis  Changing work schedules  Changing work/ activity demands  Pediatric patients requiring small insulin dosages  Special situations— menstrual cycles

35. Applications of CSII  Any person with diabetes who faces specific problems or complications Type 1 diabetes Type 2 diabetes  Loss of beta-cell reserve and endogenous insulin production  Requires a “C-peptide of less than 110 percent of the lower limit of normal of the laboratory’s measurement method”  Required by Medicare and many insurance companies

36. Patient Requirements for Pump Use  Motivated to improve control  Willingness to monitor BG 4-6 times a day  Willingness to do CHO counting  Willingness to participate in regular medical follow-up  Covered by insurance or can afford increased costs

37. Carbohydrate Counting  Insulin dosing (bolus) is based on CHO intake  Permits more exact dosing of insulin  Carbohydrate content can be easily determined  Requires familiarity with CHO vs. proteins or fats  Requires familiarity with portion sizes  Requires ability to do simple calculations  Consider referral to CDE  Direct patient to materials on CHO counting

38. Quick-carb Counting  All of the below contain approximately 15 grams of carbohydrate:  ½ cup or 4 oz of fruit juice  ½ cup canned fruit  1 cup or 8 oz of whole fresh fruit  1 slice of bread, 6 inch tortilla, 2 oz bagel  1 cup of milk  ½ cup of potatoes, rice, pasta, beans, peas

39. Reading Food Labels

40. Fat free can be misleading

41. Quick-carb Counting  Dosage of insulin is based on total grams of carbohydrates  Insulin: CHO ratio of 1:15  If the total grams of carbohydrate is 60, then 4.0 units of insulin would be administered.  Insulin: CHO ratio of 1:10  If the total grams of CHO is 60, then 6.0 units of insulin would be administered.  T2DM patients may require 1 unit for each 3-5 grams of CHO  Ex: 60 g  3 units/g = 20 units or 60 g  5 units/g = 12 units  How do you know? Test the blood glucose 2 hours post prandial

42. Correction Factor  Generally 1 unit of insulin will drop blood glucose by 30-50 points  To determine if this is true for your patient – ask them to test  Use either the 1500 or 1800 rule 1500 rule for short-acting insulin (Regular) 1800 rule for rapid-acting insulin  It is an art – not an exact science

43. Insulin Sensitivity Factor  1800 = Insulin Sensitivity Factor TDD  Example: 1800 = 50 36 units One unit of rapid-acting insulin will affect glucose by 50 mg/dL  TDD = Total Daily Dose of Insulin

44. Putting it All Together  GH is about to eat lunch. His BG is 183. He is planning to eat a salad, a six inch Subway club sandwich, a small bag of Sunchips and a diet soda.  How many CHO in this meal? How much insulin to cover the CHO?  (Imagine a 1:15 insulin to CHO ratio)  What is target pre-meal BG? How much insulin to correct for 183?  How much total insulin for this meal?

45. What Does My Patient Need to Know About Using Insulin?  Blood glucose goals and testing regimen  Insulin action profile and how insulin, physical activity and food all impact blood glucose  Signs and symptoms of hypoglycemia How to treat How to prevent  Sharps disposal  Storage of insulin

46. Finding the Right Therapy for Your Patient  Who is the patient? BG profile  Fairly stable or wide variation? Psychosocial/cultural factors Dexterity Lifestyle and willingness to adhere to regimen  About the insulin regimen Ability to mimic endogenous insulin secretion Potential adverse effect Cost Complexity

47. Summary  Timely initiation of insulin is critical  Insulin analogs most closely match normal physiology  There is a wide variety of insulin regimens and insulin delivery methods  It is important to match the insulin regimen to patient lifestyle and characteristics  When blood glucose goals are not met, titrate insulin in a timely manner  Refer to a Certified Diabetes Educator

48. Basal-Bolus, Insulin Pumps, Carbohydrate Counting, Combination Therapy Dr.Ihab Tadros Daisy Care Medical – USA The Leader in Insulin Pump Therapy And Diabetes Management