Basal-Bolus, Insulin Pumps, Carbohydrate Counting, Combination Therapy

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. Physiological Insulin Secretion Profile 75 Breakfast Lunch Dinner 50 Plasma Insulin µU/ml) 25 4:00 4:00 8:00 12:00 16:00 20:00 24:00 Time

4. Comparative Action of Insulins

5. Profiles of Human Insulins and Analogs Aspart, Glulisine, Lispro (4–5 h) Regular (6–8 h) NPH (10–16 h) Detemir, Glargine (20-24 h) Plasma insulin levels 2 4 6 8 12 14 16 18 20 22 24 0 10 Hours

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. Ideal Insulin Replacement Pattern 75 Breakfast Lunch Dinner 50 Plasma Insulin µU/ml) 25 4:00 8:00 12:00 16:00 20:00 24:00 4:00 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? • Do you add another oral agent? • Do you consider an alternative agent? • 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. Basal Insulin Bedtime Only Breakfast Lunch Dinner Plasma Insulin Detemir, Glargine 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time

14. Analog Mixed Insulin Program Breakfast Lunch Dinner Plasma Insulin 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time

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

16. Diabetes 24-Hour Plasma Glucose CurveNormal and Type 2 Diabetes 400 300 200 Glucose (mg/dL) Normal 100 0 0600 1000 1400 1800 2200 0200 0600 Time of Day NEJM 318: 1231-1239, 1988

17. ARS Question #3 • What do you do with the existing oral agents? • Continue the SU and metformin • Continue the SU but not metformin • Continue metformin but not the SU • 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? • Continue SU and metformin; give insulin detemir twice daily • Discontinue SU and metformin; give insulin detemir twice daily • Discontinue SU, add bolus insulin before largest meal (dinner) • Discontinue SU, add bolus insulin before breakfast and dinner • None of the above

20. UKPDS: β-Cell Function over 6 Years 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 -Cell Function (% ) 51% residual secretion 28% residual insulin secretion N=376 Years After Diagnosis Diabetes 44: 1249-1258, 1995 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. Physiological Insulin Secretion Profile 75 Breakfast Lunch Dinner 50 Plasma Insulin µU/ml) 25 4:00 4:00 8:00 12:00 16:00 20:00 24:00 Time

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

24. Ideal Insulin Replacement Pattern 75 Breakfast Lunch Dinner 50 Plasma Insulin µU/ml) 25 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time

25. 100 80 60 40 20 0 As Patients Get Closer to A1C Goal, the Need to Manage PPG Significantly Increases Increasing Contribution of PPG as A1C Improves % Contribution A1C Range (%) 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.

26. Aspart Aspart, Aspart, Lispro Lispro, Lispro, Glulisine Glulisine Glulisine Basal + Meal-Related Regimen Breakfast Lunch Dinner Plasma Insulin Detemir/ Glargine 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time

27. Basal Insulin: Twice Daily - AM & Bedtime Breakfast Lunch Dinner Plasma Insulin Detemir/ Glargine 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time

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? • Discontinue the SU and metformin • Discontinue the SU, continue metformin • Discontinue metformin, continue the SU • Continue the SU and metformin

31. Mrs. Blue • Discontinue the SU • Very little beta-cell reserve • No reason to give an agent to stimulate phase 2 insulin release • 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. Variable Basal Rate: CSII Program Breakfast Lunch Dinner Bolus Bolus Bolus Plasma insulin Basal infusion 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time

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

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