Dataset Information

Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.

ABSTRACT: OBJECTIVE:Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-?g/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS:Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-?g pramlintide (CL + P), after a 3-4-week outpatient dose escalation. Eleven subjects (age 18-27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3-4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS:Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS:Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.

SUBMITTER: Sherr JL

PROVIDER: S-EPMC4915555 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.

Sherr Jennifer L JL Patel Neha S NS Michaud Camille I CI Palau-Collazo Miladys M MM Van Name Michelle A MA Tamborlane William V WV Cengiz Eda E Carria Lori R LR Tichy Eileen M EM Weinzimer Stuart A SA

Diabetes care 20160505 7

<h4>Objective</h4>Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration.<h4>Research design and methods</h4>Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7.2 ...[more]

PMID: 27208332

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Project description:Background: The potential confounding effect of different amounts and proportions of macronutrients across eating patterns on meal or dietary glycemic index (GI) and glycemic load (GL) value determinations has remained partially unaddressed.Objective: The study aimed to determine the effects of different amounts of macronutrients and fiber on measured meal GI and GL values.Design: Four studies were conducted during which participants [n = 20-22; women: 50%; age: 50-80 y; body mass index (in kg/m2): 25-30)] received food challenges containing different amounts of the variable nutrient in a random order. Added to the standard 50 g available carbohydrate from white bread was 12.5, 25, or 50 g carbohydrate; 12.5, 25, or 50 g protein; and 5.6, 11.1, or 22.2 g fat from rice cereal, tuna, and unsalted butter, respectively, and 4.8 or 9.6 g fiber from oat cereal. Arterialized venous blood was sampled for 2 h, and measured meal GI and GL and insulin index (II) values were calculated by using the incremental area under the curve (AUCi) method.Results: Adding carbohydrate to the standard white-bread challenge increased glucose AUCi (P < 0.0001), measured meal GI (P = 0.0066), and mean GL (P < 0.0001). Adding protein (50 g only) decreased glucose AUCi (P = 0.0026), measured meal GI (P = 0.0139), and meal GL (P = 0.0140). Adding fat or fiber had no significant effect on these variables. Adding carbohydrate (50 g), protein (50 g), and fat (11.1 g) increased the insulin AUCi or II; fiber had no effect.Conclusions: These data indicate that uncertainty in the determination of meal GI and GL values is introduced when carbohydrate-containing foods are consumed concurrently with protein (equal amount of carbohydrate challenge) but not with carbohydrate-, fat-, or fiber-containing foods. Future studies are needed to evaluate whether this uncertainty also influences the prediction of average dietary GI and GL values for eating patterns. This trial was registered at clinicaltrials.gov as NCT01023646.

Dataset Information

Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.

Publications

Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide.

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