ISSN:
1432-0428
Keywords:
Keywords Insulin-dependent diabetes mellitus
;
amylin
;
pramlintide hyperglycaemia
;
glycaemic control
;
insulin resistance.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU · kg–1· h–1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 μg pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-μg pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-μg dose group. Peak plasma pramlintide concentrations for the 30-μg group were 21 ± 3 and 29 ± 5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the groups. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0–4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 μg, 322 ± 92 vs –38 ± 161 mmol/l · min, p = 0.010; 100 μg, 317 ± 92 vs –39 ± 76 mmol/l · min, p = 0.001; and 300 μg, 268 ± 96 vs –245 ± 189 mmol/l · min, p = 0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal. [Diabetologia (1996) 39: 492–499]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00400683
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