The role of prandial pramlintide in the treatment of adolescents with type 1 diabetes.
Pramlintide, a synthetic analog of amylin, improves postprandial hyperglycemia. We compared subcutaneous (s.c.) pramlintide injection with square wave pramlintide infusion in adolescents with type 1 diabetes (T1DM). Eight subjects with T1DM underwent two randomized studies. Subcutaneous pramlintide (dose = 5 microg/unit of insulin) bolus, was given one time and another time, the same dose was given as a 120-min s.c. infusion. Insulin dose was constant between studies. Gastric emptying was assessed with oral acetaminophen and [l-13C]glucose in meal. Plasma glucagon, pramlintide, and insulin concentrations were measured. Insulin concentrations (p < 0.99) between pramlintide injection versus infusion were similar; however, glucose concentrations were different (p < 0.0001), with the absence of hypoglycemia during pramlintide infusion [AUC (0-120 min) -0.07 +/- 0.2 versus 1.05 +/- 0.24 mg * h/dL (p < 0.0088)]. Insulin-only administration resulted in postprandial hyperglycemia and late postprandial hypoglycemia (p < 0.0001). Two subjects experienced hypoglycemia with pramlintide injection. Pramlintide bolus caused pronounced glucagon suppression (p < 0.0003) and delayed gastric emptying as ([13CO2] p < 0.0003 and acetaminophen p < 0.01) compared with infusion. We conclude that pramlintide bolus may result in an increase in risk of immediate postprandial hypoglycemia. Further modifications in pramlintide delivery are indicated before it can be safely used in children.
Rodriguez
Luisa M
LM
Department of Pediatrics, Division of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston Texas 77030, USA.
Mason
Kimberly J
KJ
Haymond
Morey W
MW
Heptulla
Rubina A
RA
D000293:Adolescent; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D058228:Islet Amyloid Polypeptide; D008297:Male; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide