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The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus

Authors
Journal
Metabolism
0026-0495
Publisher
Elsevier
Publication Date
Volume
48
Issue
7
Identifiers
DOI: 10.1016/s0026-0495(99)90232-9
Disciplines
  • Medicine

Abstract

Abstract To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 μg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 am to 4:30 pm) was performed. Serum fructosamine was decreased after pramlintide (314 ± 14 μmol/L) compared with placebo (350 ± 14 μmol/L, P = .008). On the profile day, the mean plasma glucose (8.3 ± 0.7 v 10.2 ± 0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration ( P < .01 for both) despite comparable circulating insulin levels (359 ± 41 v 340 ± 35 pmol/L). Mean blood glycerol values were reduced (0.029 ± 0.004 v 0.040 ± 0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274 ± 0.012 v 0.246 ± 0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished ( P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8 ± 7.3 v 72.4 ± 8.0 ng/L, P = .005) and lunch (47.6 ± 9.0 v 60.9 ± 8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 μg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.

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