title: 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 microg 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 x h(-1) x dl(-1), P < 0.0001). Pramlintide, but not an increase in insulin, reduced immediate postprandial hyperglycemia (AUC(0-180 min) 470 +/- 43 vs. 434 +/- 48 mg x h(-1) x 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.
authors.affiliation: Department of Pediatrics, Division of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA. heptulla@bcm.tmc.edu <heptulla@bcm.tmc.edu>
authors.forename: Rubina A
authors.initials: RA
authors.lastname: Heptulla
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Rodriguez
authors.forename: Lisa
authors.initials: L
authors.lastname: Bomgaars
authors.forename: Morey W
authors.initials: MW
authors.lastname: Haymond
mesh_terms: D000293:Adolescent; D000682:Amyloid / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide; D008297:Male
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide