Presentation on theme: "University of Washington, Seattle"— Presentation transcript:
1University of Washington, Seattle Maximizing MDIIrl B. Hirsch, M.D.University of Washington, Seattle
2First, Why is Mealtime Insulin So Important? Raise your hand if you or your child take 1 shot dailyRaise your hand if you or your child take 2 shots dailyRaise your hand if you or your child take 3 shots dailyRaise your hand if you or your child take 4 or more shots dailyRaise your hand if you or your child wear an insulin pump
3Why do so many physicians frown when they meet patients with type 1 diabetes on one or two daily injections?
4Risk for Retinopathy in Conventional and Intensive Treatment: Thinking Out of the Box Risk for Retinopathy in Subgroups of the DCCT242016128411%10%9%Mean HbA1cConventionalRate Per Patient Year8%7%Time During Study (Years)IntensiveRate Per Patient Year9%8%7%Time During Study (Years)2420161284Mean HbA1cAdapted from Diabetes 44: , 1995
5What We Now KnowThe 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 findingNew goal of therapy: improve A1c AND reduce glucose variability
6Does Intensive Therapy (Reduced GV) Preserve Beta Cell Function? 1.00.9Could some of this preservation also be related to improvement in glucose variability?0.80.7Patientprobabilityof maintaining C-peptide > 2.00.60.50.40.3Intensive therapy0.20.1Conventionaltherapy0.0123456Years Post EnrollmentNumber of evaluated patients in each treatment groupIntensive10813180533282Conventional1651506332223Adapted from: DCCT Study Group: Ann Intern Med. 1998;128:
7Trends in Average # Injections/Day, 2001-2005 U=678W=3995GfK Market Measures
8Implications? Postprandial hyperglycemia and glycemic variability Ability to proceed to more sophisticated diabetes regimensWhat are the main barriers why so many receiving insulin do so poorly?
10Who Does Best With MDI (or CSII!?) POINT 1Who Does Best With MDI (or CSII!?)Minimum of 4-6 SMBG/dayCarb counting or similar system for estimation of prandial insulin dosingFrequent SMBG can make up for poor carb estimation!Understanding basics of insulin therapy, knowing how to correct ac and pc hyperglycemia
11The Physiological Insulin Profile POINT 2The Physiological Insulin ProfileShort-lived, rapidly generated prandial insulin peaks70Normal free insulin levels from genuine data (mean)6050Insulin (mU/l)40Low, steady, basal insulin profile302010060009001200150018002100240003000600BreakfastLunchDinnerAdapted from Polonsky, et al
12Definitions for Flexible Diabetes Management Standardization of TerminologyDefinitions for Flexible Diabetes ManagementBasal insulin replacementthat insulin required to suppress hepatic glucose production over night and between mealsBolus (prandial or mealtime) insulin replacementthat insulin required to dispose of glucose in muscle after eating
13Definitions for Flexible Diabetes Management Standardization of TerminologyDefinitions for Flexible Diabetes ManagementCorrection dose (also called a supplement)additional insulin for premeal hyperglycemiacan also be between-meal hyperglycemiathis insulin can only be regular, lispro, aspart or glulisine (Humulin R, Novolin R, Humalog, Novalog, Apidra)
14Glulisine Glulisine Glulisine Basal/Bolus Treatment Program with Rapid-acting and Long-acting AnalogsBreakfastLunchDinnerAspart, Aspart, Aspart,Lispro Lispro LisproorororGlulisine Glulisine GlulisinePlasma insulinGlargineorDetemir4:008:0012:0016:0020:0024:004:008:00Time
15Does Basal Insulin Really Look Like a Flat Line?
17POINT 3In 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
18Pearls 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 mealsLower doses often require twice daily injections of basal insulinWith 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)
19Pearls with MDI: Prandial Insulin LAG timesThe amount of time between giving the prandial insulin and eating the mealDue 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
20Humalog with Different Lag Times 270230180200160Diabetes Care 22:133, 1999
21Pearls with MDI: Prandial Insulin Insulin-on-Board (IOB)
22Key Concepts Pharmacokinetics Pharmacodynamics Measurement of insulin levels after subcutaneous injectionPharmacodynamicsMeasurement of insulin action in a glucose clamp study
23Key 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 STACKINGUsing correction dose insulin to treat before-meal or between-meal hyperglycemia in a situation when there is still significant IOB
25Correction Dose (insulin sensitivity factor) The amount of glucose reduction (in mg/dL) to expect from 1 unit of insulinNumerous formulas published but in general most type 1’s start with an ISF of about 50
26ExampleTIME BG DOSE7 PM U8 PM9 PM9:30 PM 180With a target of 120 mg% and an ISF of 30, how much insulin should be provided at 9:30 pm?
27NOW what should be done with the insulin? ExampleTIME BG DOSE7 PM UIOB8 PM7.2 U9 PM5.0 U9:30 PM 1804.0 U10:00 PM UNOW what should be done with the insulin?
28So how much insulin should be given? Example210 – 120 = 90 mg/dL over targetCorrection dose = 90/30 = 3 units3.2 units on board – 3 units for correction doseSo how much insulin should be given?
29Glycemic trend trumps IOB! One can only know GT by frequent SMBG TAKE HOME POINTGlycemic trend trumps IOB!One can only know GT by frequent SMBG
30Pearls for Success Frequent SMBG (until CGM available) Knowledge of how to best use lag timesGeneral knowledge of insulin requirements for food, but with frequent SMBG not requiredKeeping track of IOBKeeping track of glycemic trend
31Some Concerning Facts¼-1/3 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 residencyThe average primary care resident doesn’t know what 1 unit of insulin is.
32Conclusion (1)After 84 years we are finally starting to understand a little about how to use insulin
33Conclusion (2)Although it is a lot of work, rewards later on are huge. Frequencies of PDR, ESRD, LEA are declining rapidly
34Conclusion (3)The number 1 barrier to type 1 diabetes therapy (especially in adults) in 2006 is…?