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Irl B. Hirsch, M.D. University of Washington, Seattle Maximizing MDI.

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Presentation on theme: "Irl B. Hirsch, M.D. University of Washington, Seattle Maximizing MDI."— Presentation transcript:

1 Irl B. Hirsch, M.D. University of Washington, Seattle Maximizing MDI

2 First, Why is Mealtime Insulin So Important? Raise your hand if you or your child take 1 shot daily Raise your hand if you or your child take 2 shots daily Raise your hand if you or your child take 3 shots daily Raise your hand if you or your child take 4 or more shots daily Raise your hand if you or your child wear an insulin pump

3 Why do so many physicians frown when they meet patients with type 1 diabetes on one or two daily injections?

4 Risk for Retinopathy in Conventional and Intensive Treatment: Thinking Out of the Box Conventional Adapted from Diabetes 44: , % Rate Per Patient Year 10% 9% 8% 7% Time During Study (Years) Mean HbA1c Risk for Retinopathy in Subgroups of the DCCT Intensive Rate Per Patient Year 9% 8% 7% Time During Study (Years) Mean HbA1c

5 What We Now Know The more up AND down the more damage to cells through a mechanism called oxidative stress Most of this is based on very basic science data, but clinical studies now supporting this finding New goal of therapy: improve A1c AND reduce glucose variability

6 Does Intensive Therapy (Reduced GV) Preserve Beta Cell Function? Adapted from: DCCT Study Group: Ann Intern Med. 1998;128: Years Post Enrollment Number of evaluated patients in each treatment group Intensive Conventional Conventional therapy Intensive therapy Patient probability of maintaining C-peptide > 2.0 Could some of this preservation also be related to improvement in glucose variability?

7 Trends in Average # Injections/Day, GfK Market Measures U=678 W=3995

8 Implications? Postprandial hyperglycemia and glycemic variability Ability to proceed to more sophisticated diabetes regimens What are the main barriers why so many receiving insulin do so poorly?

9 Basics of MDI: What to Consider

10 Who Does Best With MDI (or CSII!?) Minimum of 4-6 SMBG/day Carb counting or similar system for estimation of prandial insulin dosing Frequent SMBG can make up for poor carb estimation! Understanding basics of insulin therapy, knowing how to correct ac and pc hyperglycemia POINT 1

11 The Physiological Insulin Profile Adapted from Polonsky, et al Insulin (mU/l) Short-lived, rapidly generated prandial insulin peaks Low, steady, basal insulin profile Normal free insulin levels from genuine data (mean) BreakfastLunchDinner POINT 2

12 Definitions for Flexible Diabetes Management Basal insulin replacement that insulin required to suppress hepatic glucose production over night and between meals Bolus (prandial or mealtime) insulin replacement that insulin required to dispose of glucose in muscle after eating Standardization of Terminology

13 Definitions for Flexible Diabetes Management Correction dose (also called a supplement) additional insulin for premeal hyperglycemia can also be between-meal hyperglycemia this insulin can only be regular, lispro, aspart or glulisine (Humulin R, Novolin R, Humalog, Novalog, Apidra) Standardization of Terminology

14 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Glargine or Detemir Lispro Lispro Lispro Aspart, Aspart, Aspart, or Plasma insulin Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs Glulisine Glulisine Glulisine

15 Does Basal Insulin Really Look Like a Flat Line?

16 Klein et al: 325-OR, ADA, 2006

17 POINT 3 In general, 40-50% of insulin should be basal insulin glargine (Lantus), insulin detemir (Levemir), or delivery from a pump and the rest should be mealtime (bolus) insulin

18 Pearls with MDI Basal Insulin Basal insulin approximately 40-50% total daily insulin dose (TDD) Basal insulin best assessed by fasting glucose levels and glycemic curves with missed meals Lower doses often require twice daily injections of basal insulin With MDI, most patients prefer pens for prandial insulin; however, less likely to make an error in insulin if basal insulin used is vial (or at least pens are different brands)

19 Pearls with MDI: Prandial Insulin LAG times The amount of time between giving the prandial insulin and eating the meal Due to the timing of insulin absorption compared to carbohydrate absorption, insulin usually needs to be injected a minimum of 10 min prior to eating, even if glucose levels are within target. Longer lag times are required for pre-meal hyperglycemia

20 Humalog with Different Lag Times Diabetes Care 22:133,

21 Pearls with MDI: Prandial Insulin Insulin-on-Board (IOB)

22 Key Concepts Pharmacokinetics Measurement of insulin levels after subcutaneous injection Pharmacodynamics Measurement of insulin action in a glucose clamp study

23 Key Concepts INSULIN-ON-BOARD (IOB, insulin remaining) The amount of insulin from the last prandial dose which has not yet been absorbed based on insulin action (not insulin blood levels) INSULIN STACKING Using correction dose insulin to treat before-meal or between-meal hyperglycemia in a situation when there is still significant IOB

24 % insulin remaining Insulin lispro (Humalog) and insulin aspart (NovoLog) insulin action disappearance curves

25 Correction Dose (insulin sensitivity factor) The amount of glucose reduction (in mg/dL) to expect from 1 unit of insulin Numerous formulas published but in general most type 1s start with an ISF of about 50

26 Example TIMEBGDOSE 7 PM 95 8 U 8 PM 9 PM 9:30 PM180 With a target of 120 mg% and an ISF of 30, how much insulin should be provided at 9:30 pm?

27 Example TIMEBGDOSE 7 PM 95 8 U 8 PM 9 PM 9:30 PM180 IOB 7.2 U 5.0 U 4.0 U 10:00 PM U NOW what should be done with the insulin?

28 Example 210 – 120 = 90 mg/dL over target 3.2 units on board – 3 units for correction dose Correction dose = 90/30 = 3 units So how much insulin should be given?

29 TAKE HOME POINT Glycemic trend trumps IOB! One can only know GT by frequent SMBG

30 Pearls for Success Frequent SMBG (until CGM available) Knowledge of how to best use lag times General knowledge of insulin requirements for food, but with frequent SMBG not required Keeping track of IOB Keeping track of glycemic trend

31 Some Concerning Facts ¼-1/3 of those with T1DM are still taking 1 or 2 shots daily-shown ineffective in 1993 < 20% of T1DM in US with A1c < 7% Insulin therapy is not taught in medical schools or residency The average primary care resident doesnt know what 1 unit of insulin is.

32 Conclusion (1) After 84 years we are finally starting to understand a little about how to use insulin

33 Conclusion (2) Although it is a lot of work, rewards later on are huge. Frequencies of PDR, ESRD, LEA are declining rapidly

34 Conclusion (3) The number 1 barrier to type 1 diabetes therapy (especially in adults) in 2006 is…?


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