3After-Meal Peaks Defined The net rise that occurs from before eating to the highest point after eating.ADA Goal:<10 mmol 1-2 hrs after start of mealAACE Target:<7.8 mmol at peakEuropean Diabetes Policy Group:<9 mmol (to prevent complications)International Diabetes Federation:< 7.8 mmol 2 hrs after meal
4After-Meal Goals for Children Under 5 Years:1 hr. post-meal(<6.7 mmol Rise)5-11 Years:1 hr. post-meal(<5.5 mmol Rise)12 Years +< 1 hr. post-meal(<4.4 mmol Rise)
5After-Meal Peaks: Reality for children Source: Boland et al, Diabetes Care 24: 1858, 2001
6After-Meal Peaks: Reality in Children Source: Boland et al, Diabetes Care 24: 1858, 2001
8After-Meal Highs: Immediate Problems Australian Study of Children w/Type 1. Parents & children reported BG > 15 had negative impact on:Thinking (68%)Mood/Emotions (75%)Coordination (53%)J Pediatr Endocrinol Metab Jul;19(7);
9Long-Term Problems Relative Influence on HbA1c Source: Monnier et al, Diabetes Care, 26, 3/03,
10Long-Term Problems (contd) 52 Type 1’s, similar BP between groupsPost-prandial glucoseRangeTime to onset of proteinuriaPersistent <1123 yrsIntermittent >1119 yrsPersistent > 11>1114 yrsSource: Kidney Intl. 1987; 32 (supp 22): S53-S56
11Long-Term Problems (contd) 22-yr CVD Mortality Risk by Baseline post-challenge glucoseSource: Chicago Heart Study, Lowe et al, Diabetes Care, 1997; 20:
12Long-Term Problems (contd) Rates of eye and kidney disease based on glucose variability (using CGM) in Type-2 DiabetesSource: Liu et al, American Diabetes Association 71st Scientific Sessions 2011, Abstract 2205-PO.
14Measurement of After-Meal Peaks SMBGCapillary (finger) testAfter completion of mealCheck BG 1 Hr PP(or) every 15, 20 or 30 min until 2 consecutive BG drops occurNo addl. Food/insulin until test is completed
15Meter Test Example Brea kfast Lun ch Din ner Pre 1h Post 6.1 15.2 5.5 9.210.711.25.016.12.9188.8.131.52.514.74.08.813.3Interpretation:Excessive after-meal peak following breakfast; not after lunch or dinner
16Meter Test Example Time pp BG Value Interpretation: Premeal 6.8 ::1:1:1:2:Interpretation:Peak occurred at 1hr, 20min pp; rise from premeal to peak was approx. 5 mmol
17Measurement of After-Meal Peaks iPro CGM (Medtronic)Worn for 72 hrs, then data is downloaded for analysis
18Measurement of After-Meal Peaks Real-Time Continuous Glucose MonitorsAllow tracking of post-meal trendsProduce BG estimates every 1-5 minutes
24Glycemic IndexAll carbs (except fiber) convert to blood glucose eventuallyG.I. Reflects the magnitude of blood glucose rise for the first 2 hours following ingestionG.I. Number is % or rise relative to pure glucose (100% of glucose is in bloodstream within 2 hours)
25Glycemic Index (contd.) Example:SpaghettiGI = 37Only 37% of spaghetti’s carbs turn into blood glucose in the first 2 hours.The rest will convert to blood glucose over the next several hours.
26Glycemic Index (contd) Parillo M et al. Effects of meals with different glycaemic index on postprandial blood glucose response in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion. Diabet Med; 2011 Feb;28(2):227-9
27Dietary Intervention Use of Glycemic Index Lower GI foods digest & convert to glucose more slowlyHigh-fiber slower than lowHi-fat slower than lowSolids slower than liquidsCold foods slower than hotType of sugar/starch affects GI
28Glycemic Index (contd.) Slow StuffAverage StuffFast StuffPastaLegumesSalad VeggiesDairyChocolateFruitJuicePizzaSoupCakeBreads/CrackersSalty SnacksPotatoesRiceCerealsSugary Candies
29Examples: Use of GI Meal High-GI Options Low-GI Options Breakfast Examples: Use of GIMealHigh-GI OptionsLow-GI OptionsBreakfastCereal, Bagel, Waffle, Pancakes, MuffinsOatmeal, Milk,Whole FruitLunchWhite Bread, Fries, Tortillas, CupcakeSourdough/Pumpernickel, Yogurt, Corn, CarrotsSnacksPretzels, Chips, Crackers, DoughnutsFruit, Popcorn, Nuts, Ice Cream, ChocolateDinnerRice, Mashed or Baked Potatoes, RollsPasta, Peas, Beans, Sweet Potato, Salad Veggies
30Add Some Acidity 60-min glucose response 55%* TomatoesSourdoughVinegar (Salad Dressing/Condiments)*Journal of the American Dietetic Association, 2005: v7 no12.
31Split The Meal Part at the usual mealtime Part minutes later
32 Meal Sequences Eat veggies before starch when having mixed meals Eat veggies before starch when having mixed mealsMake lunch the “higher carb” meal (less at breakast & dinner)Presented at the American Diabetes Associaion Scientific Sessions, 2012, symposium on minimizing glucose variability.
35Timing of Bolus Insulin (humalog/novolog)High GIModerate GILow GIBG Above Target Range30-40 min. prior15-20 min. prior0-5 min. priorBG Within Target Range15-20 min. afterBG Below Target Range30-40 min. after
36Does Timing Matter? Note: Carbs estimated w/pre-meal insulin. Carbs known with post-meal insulin.Source: Clinical Therapeutics 2004; 26:
38Does Timing Matter? Insulin taken with meal Insulin taken min Pre-Meal (if >150)A1cDuran-Valdez, et al (U of New Mexico). Insulin Timing—A Beneficial Addition to Intensive Insulin Therapy in Type-1 Diabetes. Presented at the American Diabetes Association Scientific Sessions 2012, poster 964-P.
39Insulin Delivery Method Jet InjectionVs.Needle Injection31 Minutes to PeakPeak conc. 108 mU/LSame total absorptionSame total action105 Minutes to PeakPeak conc. 79 mU/LEngwerda et al, Diabetes Care, 2011
40Warming The Injection/Infusion Site “Insupatch” (experimental)Heating element in pump infusion siteWarms site to 38-40C30-40 minute earlier insulin peak
44Injectible Symlin (Amylin Pharmaceuticals) IssuesNauseaMust be injected*, cannot mix w/insulinInsulin doses must be adjusted, delayedNot yet FDA approved for children* pumped???
45Effect of Pramlintide on Gastric Emptying in Type 1 Diabetes BreakfastInsulin + PlaceboInsulin + Pramlintide4**~1-h delay3DISCUSSION POINTS:Pramlintide slows gastric emptying of the solid portion of a standard meal in subjects with type 1 diabetes.Gastric emptying is the rate-limiting step that regulates glucose delivery from the GI tract into the bloodstream.The effects of pramlintide, seen at the first meal, were no longer present at a subsequent meal.SLIDE BACKGROUND:Double-blind, randomized, crossover study (n = 11 males with type 1 diabetes).Participants self-injected their usual dose of insulin and 15 min later, self-injected either placebo, 30 µg pramlintide, or 60 µg pramlintide prior to the first of 2 meals issued.Study participants then ate a standard meal (a radio-labeled pancake and milkshake). Radio images of the stomach were obtained for the next 8 h.Data presented are mean SEM.Mean Half-Emptying Time (h)21Placebo30 µg60 µgSingle SC pramlintide doses: n = 11, crossover; *P<0.004;99m Tc labelled pancake; solid component measured Data from Kong MF, et al. Diabetologia 1998; 41:
46Pramlintide Reduces Postprandial Glucagon Type 2 Diabetes, Late StageType 1 DiabetesPlaceboPramlintideInsulinInsulinSustacal®30Sustacal®6020DISCUSSION POINTS:Pramlintide reduces postprandial glucagon secretion in insulin-using patients with both type 2 and type 1 diabetes.This slide demonstrates the effect of intravenous infusion of pramlintide on postprandial glucagon in 2 separate studies involving insulin-using patients with type 2 diabetes (left figure) and type 1 (right figure) diabetes.SLIDE BACKGROUND:Left figure: Crossover design study; insulin-treated patients with type 2 diabetes (n = 12) were infused with either pramlintide (100 g/h) or placebo for 5 h during a SUSTACAL® meal challenge test.Right figure: Crossover study design; patients with type 1 diabetes (n = 9) infused with pramlintide (25 g/h) or placebo for 5 h during a SUSTACAL® meal challenge test.In both studies, pramlintide or placebo was infused at t = 0 min, regular insulin injected at t = 30 min, and SUSTACAL® meal ingested at t = 60 min. Data presented are mean ( SE) plasma glucagon (pg/mL).A similar study, conducted in non-insulin-using patients with type 2 diabetes, yielded similar results.SUSTACAL® is a registered trademark of Mead Johnson.5010Plasma Glucagon (pg/mL) Plasma Glucagon (pg/mL)40-1030Placebo or 100 µg/h pramlintide infusion12345Placebo or 25 µg/h pramlintide infusion-2012345Time (h)Time (h)Type 2 diabetes, n = 12; AUC1-4 h: P = 0.005Type 1 diabetes, n = 9; AUC1-5 h: P<0.001;Data from: Fineman M, et al. Metabolism 2002; 51: ; Fineman M, et al. Horm Metab Res 2002; 34:
47Pramlintide Reduces Caloric Intake in Type 2 Diabetes 1250-202 kcal(-23%)P <0.01PlaceboPramlintide1000DISCUSSION POINTS:Pramlintide reduced mean caloric intake and macronutrient intake during a buffet study in subjects with type 2 diabetes.SLIDE BACKGROUND:In a randomized, double-blind, placebo (PBO)-controlled, crossover study, subjects underwent a standardized buffet meal test on 2 occasions. After an overnight fast, subjects received a single SC injection of pramlintide (120 g) or PBO, immediately followed by a standardized preload meal. After 1 h, subjects were offered an ad-libitum buffet meal. Total caloric intake (TCI) and meal duration were measured.750CHOAd-LibitumCaloric Intake(kcal)CHO500FatFat250ProteinProteinn = 11; subjects given buffet meal Pramlintide (single SC injection, 120 g) Data from Chapman I, et al. Diabetologia 2005; 48:
48Pre-Meal Hypoglycemia “Sieve Effect”Accelerates gastric emptying of liquids and solidsProduces more rapid BG rise after mealJ Clin Endo Metab 2005; 90:A v o i d P r e – M e a l L o w s !
49Physical Activity Intervention Muscle Use Soon After EatingAccelerated Delayed Glucose Uptake/Insulin Absorption Digestion UtilizationImproved After-Meal Control
50Effects of Post-Meal Walking 30 Minutes of casual stop & go walking after mealsAvg. 30 mg/dl (1.75 mmol/L) BG reductionPeak post-meal glucose 45% higher when not walkingKudva, et al. Diabetes Care, published online Aug 8, 2012