The Role of Amylin and Glucagon in the Dampening of Glycemic Excursions in Children With Type 1 Diabetes

Abstract

Postprandial hyperglycemia and preprandial hypoglycemia contribute to poor glycemic control in type 1 diabetes. We hypothesized that postprandial glycemic excursions could be normalized in type 1 diabetes by suppressing glucagon with pramlintide acetate in the immediate postprandial period and supplementing glucagon in the late postprandial period. A total of 11 control subjects were compared with 8 type 1 diabetic subjects on insulin pump therapy, using the usual insulin bolus–to–carbohydrate ratio during a standard liquid meal. Type 1 diabetic subjects were then randomized to two open-labeled studies. On one occasion, type 1 diabetic subjects received a 60% increase in the insulin bolus–to–carbohydrate ratio with minidose glucagon rescue injections, and on the other occasion type 1 diabetic subjects received 30–45 μg pramlintide with their usual insulin bolus–to–carbohydrate ratio. Glucose, glucagon, amylin (pramlintide), and insulin concentrations were measured for 420 min. The plasma glucose area under the curve (AUC) for 0–420 min was lower in control versus type 1 diabetic subjects (316 ± 5 vs. 929 ± 18 mg · h−1 · dl−1, P < 0.0001). Pramlintide, but not an increase in insulin, reduced immediate postprandial hyperglycemia (AUC0–180 min 470 ± 43 vs. 434 ± 48 mg · h−1 · dl−1, P < 0.01). Pramlintide administration suppressed glucagon (P < 0.02), and glucagon injections prevented late hypoglycemia with increased insulin. In summary, in type 1 diabetes, glucagon modulation with pramlintide as an adjunct to insulin therapy may prove beneficial in controlling postmeal glycemic swings.