The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus.
OBJECTIVE
Amylin is a second beta-cell hormone that is normally co-secreted with insulin in response to meals; it complements the effects of insulin in postprandial glucose control, in part by suppressing glucagon secretion. In patients with type 2 diabetes, mealtime administration of the human amylin analog pramlintide markedly improves postprandial glucose excursions. The aim of this study was to examine whether pramlintide reduces the postprandial hyperglucagonemia that is often seen in this patient population.


METHODS
Utilizing a single-blind, placebo-controlled crossover design, 24 patients with type 2 diabetes, 12 insulin-treated and 12 non-insulin-treated, underwent a standardized mixed meal test on 2 occasions during which they received, in randomized order, a five-hour intravenous infusion of placebo or pramlintide (100 microg/h).


RESULTS
During the placebo infusion, plasma glucose and plasma glucagon concentrations increased substantially after the meal. During the pramlintide infusion, postprandial plasma glucose and plasma glucagon responses were significantly (p < 0.05, all) reduced following ingestion of the same meal, both in the insulin-treated and non-insulin-treated subgroups.


CONCLUSIONS
Supplementation of mealtime amylin with pramlintide reduces postprandial hyperglucagonemia in patients with type 2 diabetes, a mechanism that likely contributes to pramlintide's postprandial glucose-lowering effect.
Fineman
M
M
Amylin Pharmaceuticals, Inc, San Diego, California 92121, USA. mfineman@amylin.com
Weyer
C
C
Maggs
D G
DG
Strobel
S
S
Kolterman
O G
OG
D000328:Adult; D000682:Amyloid / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide