gregory o. clark, md - jdrf · understanding your insulin activity curve—aka your crystal ball(or...
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Understanding your Insulin Activity Curve—AKAYour Crystal Ball (or Timing is Everything!)
Gregory O. Clark, MD
CHICAGO DIABETES EXPERTSThursday, February 23, 2017
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Type 1 Diabetes—Controlled or Not?
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Type 1 Diabetes– Controlled, Really?!
Avgglucose
140 =
A1c ~7
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What We Expect
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A Better Reflection of Reality
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Problems In Type 1
Glucose variability
Glucagon excess, esp. post‐meal
Insulin deficiency, less than ideal injected insulin
Western Diet, large meals, carbohydrate heavy
Liver overproduction of glucose
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Islet Architecture
Type 1 Diabetes NormalGlucagon excess Insulin predominates
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Insulin
Glucagon
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Subcutaneous insulin leads to whole body insulin excess
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Normal is the Problem
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Principles of Intensive Therapy ofType 1 DiabetesInsulin Options
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Lepore M. Diabetes. 2000;49:2142-48; Porcellati F. Diabetes Care. 2007;30:2447-52; Plank J. Diabetes Care. 2005;28: 1107-12; Mudaliar SR. Diabetes Care 1999;22:1501-06; Becker RHA. Exp Clin Endocrinol Diab 2005;113:435-443
Action Profiles of Insulins
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Insulin Action
Regular 6–8 hoursNPH 12–18 hours
Hours
Lantus >24 hours
Humalog, Novolog, Apidra ~4 hours
Levemir 12-24 hours
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Basal insulin Controls glucose production between meals and overnight Near‐constant levels Usually ~50% of daily needs
Bolus insulin (mealtime or prandial) Limits hyperglycemia after meals Immediate rise and sharp peak at 2 hours postmeal 10% to 20% of total daily insulin requirement at each meal
Physiologic Multiple Injection RegimensThe Basal‐Bolus Insulin Concept
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Plasma
Insulin
(U/mL)
Time4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00
Breakfast Lunch Dinner
Glargine/Levemir
Lispro/Aspart/Glulisine
75
50
25
0Adapted from Skyler J, Kelley’s Textbook of Internal Medicine. 2000.
Insulin Absorption Pattern with Intensive Insulin Therapy
Basal and Bolus
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Variable Basal Rate Continuous Subcutaneous Insulin Infusion (CSII) Program‐uses Rapid Acting
Insulin
4:00
25
50
75
16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Plas
ma
Insu
lin µ
U/m
l)
8:0012:008:00Time
Bolus Bolus Bolus
Basal Infusion
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No Repeating Pattern
30 yo female - Continuous glucose tracings for 21 days –A1c 7.5
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Action Profile of “Rapid” InsulinHere is your Crystal Ball
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Insulin Action
Hours
Humalog, Novolog, Apidra ~4 hours
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Lepore M. Diabetes. 2000;49:2142-48; Porcellati F. Diabetes Care. 2007;30:2447-52; Plank J. Diabetes Care. 2005;28: 1107-12; Mudaliar SR. Diabetes Care 1999;22:1501-06; Becker RHA. Exp Clin Endocrinol Diab 2005;113:435-443
Action Profiles of Insulins
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Insulin Action
Hours
Humalog, Novolog, Apidra 4–5 hours
2 hours to peak is not “fast”
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CarbsDeliciousNutritious
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Carbohydrates – Some are Only Delicious
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A Glucose Spike with Every MealG
luco
se
B L D
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Pure Carbs Meals are Most Tricky
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Use of Advance Insulin
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When Do You Think This Patient Started Using Insulin In Advance of Meals?
24
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Delay the Meal After Insulin if Glucose is High
A lower glucose at the start of a meal reduces glucose exposure.
Rules:
Test early
Bolus early
Don’t forget to eat on time
Don’t forget you’ve already bolused
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Proteins and Fats are not Free!
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ProteinsIntermediate Effect on Blood Glucose
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FATS ARE SLOOOOOOW…..
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Lepore M. Diabetes. 2000;49:2142-48; Porcellati F. Diabetes Care. 2007;30:2447-52;
Plank J. Diabetes Care. 2005;28: 1107-12; Mudaliar SR. Diabetes Care 1999;22:1501-06;
Becker RHA. Exp Clin Endocrinol Diab 2005;113:435-443
Action Profiles of Insulins
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Insulin
Action
Hours
Humalog, Novolog, Apidra 4–5 hours
4 hours often not long enough for food effect
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High Carb + High fatCarbs Spike FastFats Keep You Up
Carbs
Fat kicking in as rapid insulin wears off
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The Ultimate Test!
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Insulin Action
Hours2pm 530pm 9pm 6am100 160 120 90
6 units 4 2 + 10% ↑ basal
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The Ultimate Test
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Minimize Variables to Minimize Variance
Variables: food and insulin
If the doses of food and insulin are kept small, the variance in blood glucose is minimized
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My strategy for success
A protein and 2 veggiesVeggies are very important!
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This is More Flat than People Without Diabetes
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Low Carbohydrate Diets are Often an Important Consideration
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New Devices Make It Easier to Remember Where You Are on the Insulin Activity Curve
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Lepore M. Diabetes. 2000;49:2142-48; Porcellati F. Diabetes Care. 2007;30:2447-52; Plank J. Diabetes Care. 2005;28: 1107-12; Mudaliar SR. Diabetes Care 1999;22:1501-06; Becker RHA. Exp Clin Endocrinol Diab 2005;113:435-443
Action Profiles of InsulinsEven Basal Insulins Require Consideration
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
InsulinAction
Hours
Glargine >24 hours
Detemir 12-24 hours
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Thank you!
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