Strategies for Combatting After-Meal Highs Gary Scheiner MS, CDE Strike The Spike! Strategies for Combatting After-Meal Highs Gary Scheiner MS, CDE

Overview Definitions Risks Detection Management

After-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 meal AACE Target: <7.8 mmol at peak European Diabetes Policy Group: <9 mmol (to prevent complications) International Diabetes Federation: < 7.8 mmol 2 hrs after meal

After-Meal Goals for Children Under 5 Years: <14 @ 1 hr. post-meal (<6.7 mmol Rise) 5-11 Years: <12.5 @ 1 hr. post-meal (<5.5 mmol Rise) 12 Years + < 11 @ 1 hr. post-meal (<4.4 mmol Rise)

After-Meal Peaks: Reality for children Source: Boland et al, Diabetes Care 24: 1858, 2001

After-Meal Peaks: Reality in Children Source: Boland et al, Diabetes Care 24: 1858, 2001

After-Meal Highs: Immediate Problems Tiredness Difficulty Concentrating Impaired Athletic Performance Decreased desire to move Mood Shifts Enhanced Hunger

After-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. 2006 Jul;19(7); 927-36

Long-Term Problems Relative Influence on HbA1c Source: Monnier et al, Diabetes Care, 26, 3/03, 881-885

Long-Term Problems (contd) 52 Type 1’s, similar BP between groups Post-prandial glucose Range Time to onset of proteinuria Persistent <11 6.1-11.0 23 yrs Intermittent >11 6.6-12.7 19 yrs Persistent > 11 >11 14 yrs Source: Kidney Intl. 1987; 32 (supp 22): S53-S56

Long-Term Problems (contd) 22-yr CVD Mortality Risk by Baseline post-challenge glucose Source: Chicago Heart Study, Lowe et al, Diabetes Care, 1997; 20: 163-170.

Long-Term Problems (contd) Rates of eye and kidney disease based on glucose variability (using CGM) in Type-2 Diabetes Source: Liu et al, American Diabetes Association 71st Scientific Sessions 2011, Abstract 2205-PO.

Measurement of After-Meal Peaks SMBG Capillary (finger) test After completion of meal Check BG 1 Hr PP (or) every 15, 20 or 30 min until 2 consecutive BG drops occur No addl. Food/insulin until test is completed

Meter Test Example Brea kfast Lun ch Din ner Pre 1h Post 6.1 15.2 5.5 9.2 10.7 11.2 5.0 16.1 2.9 13.1 5.4 7.9 7.5 14.7 4.0 8.8 13.3 Interpretation: Excessive after-meal peak following breakfast; not after lunch or dinner

Meter Test Example Time pp BG Value Interpretation: Premeal 6.8 :20 6.9 :40 8.2 1:00 11.3 1:20 11.7 1:40 10.4 2:00 9.9 Interpretation: Peak occurred at 1hr, 20min pp; rise from premeal to peak was approx. 5 mmol

Measurement of After-Meal Peaks iPro CGM (Medtronic) Worn for 72 hrs, then data is downloaded for analysis

Measurement of After-Meal Peaks Real-Time Continuous Glucose Monitors Allow tracking of post-meal trends Produce BG estimates every 1-5 minutes

CGMS Case Study 37 year old man

CGMS Case Study 8 year old girl

CGMS Case Studies 12 year old boy

1,5 – anhydroglucitol “GlycoMark” Spike Measurement 1,5 – anhydroglucitol “GlycoMark” Laboratory Blood Test Measures Duration & Magnitude of High BG Excursions for past 10-14 days “Normal” is >14 g/ml

After-Meal Spike Reduction Lifestyle Approaches Medicinal Approaches

Glycemic Index All carbs (except fiber) convert to blood glucose eventually G.I. Reflects the magnitude of blood glucose rise for the first 2 hours following ingestion G.I. Number is % or rise relative to pure glucose (100% of glucose is in bloodstream within 2 hours)

Glycemic Index (contd.) Example: Spaghetti GI = 37 Only 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.

Glycemic 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

Dietary Intervention Use of Glycemic Index Lower GI foods digest & convert to glucose more slowly High-fiber slower than low Hi-fat slower than low Solids slower than liquids Cold foods slower than hot Type of sugar/starch affects GI

Glycemic Index (contd.) Slow Stuff Average Stuff Fast Stuff Pasta Legumes Salad Veggies Dairy Chocolate Fruit Juice Pizza Soup Cake Breads/Crackers Salty Snacks Potatoes Rice Cereals Sugary Candies

Examples: Use of GI   Meal High-GI Options Low-GI Options Breakfast   Examples: Use of GI Meal High-GI Options Low-GI Options Breakfast Cereal, Bagel, Waffle, Pancakes, Muffins Oatmeal, Milk, Whole Fruit Lunch White Bread, Fries, Tortillas, Cupcake Sourdough/Pumpernickel, Yogurt, Corn, Carrots Snacks Pretzels, Chips, Crackers, Doughnuts Fruit, Popcorn, Nuts, Ice Cream, Chocolate Dinner Rice, Mashed or Baked Potatoes, Rolls Pasta, Peas, Beans, Sweet Potato, Salad Veggies

Add Some Acidity 60-min glucose response 55%* Tomatoes Sourdough Vinegar (Salad Dressing/Condiments) *Journal of the American Dietetic Association, 2005: v7 no12.

Split The Meal  Part at the usual mealtime  Part 60-90 minutes later

   Meal Sequences Eat veggies before starch when having mixed meals    Eat veggies before starch when having mixed meals Make lunch the “higher carb” meal (less at breakast & dinner) Presented at the American Diabetes Associaion Scientific Sessions, 2012, symposium on minimizing glucose variability.

Choice of Bolus Insulin Humalog Novorapid or Apidra Vs. Regular Insulin 1-hr. peak 3-4 hr. effective duration 2-3 hr. peak 4-6 hr. effective duration

Timing of Bolus Insulin

Timing of Bolus Insulin (humalog/novolog) High GI Moderate GI Low GI BG Above Target Range 30-40 min. prior 15-20 min. prior 0-5 min. prior BG Within Target Range 15-20 min. after BG Below Target Range 30-40 min. after

Does Timing Matter? Note: Carbs estimated w/pre-meal insulin. Carbs known with post-meal insulin. Source: Clinical Therapeutics 2004; 26:1492-7.

Does Timing Matter? Bolus w/meal Bolus pre-meal

Does Timing Matter?  Insulin taken with meal  Insulin taken 15-30 min Pre-Meal (if >150) A1c Duran-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.

Insulin Delivery Method Jet Injection Vs. Needle Injection 31 Minutes to Peak Peak conc. 108 mU/L Same total absorption Same total action 105 Minutes to Peak Peak conc. 79 mU/L Engwerda et al, Diabetes Care, 2011

Warming The Injection/Infusion Site “Insupatch” (experimental) Heating element in pump infusion site Warms site to 38-40C 30-40 minute earlier insulin peak

Warming The Injection/Infusion Site

Choice of Insulin Program Lantus & MDI Vs. Daytime isophane Meal/snack boluses Prolonged peak covers midday meals/snacks

Injectible Symlin (Amylin Pharmaceuticals) Acts on CNS  Appetite Slows gastric emptying Inhibits glucagon secretion Really flattens postprandial BGs

Injectible Symlin (Amylin Pharmaceuticals) Issues Nausea Must be injected*, cannot mix w/insulin Insulin doses must be adjusted, delayed Not yet FDA approved for children * pumped???

Effect of Pramlintide on Gastric Emptying in Type 1 Diabetes Breakfast Insulin + Placebo Insulin + Pramlintide 4 * * ~1-h delay 3 DISCUSSION 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) 2 1 Placebo 30 µg 60 µg Single SC pramlintide doses: n = 11, crossover; *P<0.004; 99m Tc labelled pancake; solid component measured Data from Kong MF, et al. Diabetologia 1998; 41:577-583

Pramlintide Reduces Postprandial Glucagon Type 2 Diabetes, Late Stage Type 1 Diabetes Placebo Pramlintide Insulin Insulin Sustacal® 30 Sustacal® 60 20 DISCUSSION 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. 50 10 Plasma Glucagon (pg/mL)  Plasma Glucagon (pg/mL) 40 -10 30 Placebo or 100 µg/h pramlintide infusion 1 2 3 4 5 Placebo or 25 µg/h pramlintide infusion -20 1 2 3 4 5 Time (h) Time (h) Type 2 diabetes, n = 12; AUC1-4 h: P = 0.005 Type 1 diabetes, n = 9; AUC1-5 h: P<0.001; Data from: Fineman M, et al. Metabolism 2002; 51:636-641; Fineman M, et al. Horm Metab Res 2002; 34:504-508

Pramlintide Reduces Caloric Intake in Type 2 Diabetes 1250 -202 kcal (-23%) P <0.01 Placebo Pramlintide 1000 DISCUSSION 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. 750 CHO Ad-Libitum Caloric Intake (kcal) CHO 500 Fat Fat 250 Protein Protein n = 11; subjects given buffet meal Pramlintide (single SC injection, 120 g) Data from Chapman I, et al. Diabetologia 2005; 48:838-848

Pre-Meal Hypoglycemia “Sieve Effect” Accelerates gastric emptying of liquids and solids Produces more rapid BG rise after meal J Clin Endo Metab 2005; 90: 4489-95 A v o i d P r e – M e a l L o w s !

Physical Activity Intervention Muscle Use Soon After Eating Accelerated Delayed Glucose Uptake/ Insulin Absorption Digestion Utilization Improved After-Meal Control

Effects of Post-Meal Walking 30 Minutes of casual stop & go walking after meals Avg. 30 mg/dl (1.75 mmol/L) BG reduction Peak post-meal glucose 45% higher when not walking Kudva, et al. Diabetes Care, published online Aug 8, 2012

Examples: After-Meal/Snack Activity Walking Pets Household Chores Planned Exercise Yard Work Gym Class??? Shooting Hoops Dancing Bowling Mini Golf Skating

Examples: After-Meal/Snack Activity “Free Time With Siblings”

Summary After-Meal Blood Sugar Levels Are: Important to Control Measurable Manageable

For More Information: Gary Scheiner MS, CDE Integrated Diabetes Services (USA) 877-735-3648 (USA) (877-SELF-MGT) Website: www.integrateddiabetes.com E-mail: gary@integrateddiabetes.com