Overnight GLP-1 normalizes fasting but not daytime plasma glucose levels in NIDDM patients

Summary

GLP-1 (7 — 36 amide) normalizes fasting plasma glucose in NIDDM patients. It was the aim to study the effect of overnight intravenous GLP-1 (7-36 amide) on the following 24 h-glucose profiles. Ten NIDDM patients (7 female, 3 male; age 62 ± 4 y., BMI (Body-Mass-Index) 29.6 ± 3.9 kg/m², duration 10 ± 7 y., HbA_lc 10.9 ± 1.3% (normal 4.0—6.1%), treated with glibenclamide and/or metformin) were studied on two occasions in random order: Either GLP-1 (7-36 amide) (Saxon Biochemicals, Hannover, FRG, 1 pmol • kg⁻¹ • min⁻¹) or placebo (0.9% NaCl with 1% human serum albumin, Behringwerke, Marburg, FRG) were infused intravenously from 22⁰⁰ to 7⁰⁰ (9 h) and plasma glucose profiles were obtained during the GLP-1 infusion and the following 24 hours. GLP-1 (7-36 amide) (plasma concentration 110 ± 12 pmol/1) raised plasma Cpeptide concentrations (p = 0.0005), suppressed glucagon (p = 0.01) and lowered plasma glucose to 5.5 ± 0.6 and 6.3 ± 0.4 mmol/1 at 3⁰⁰ and 7⁰⁰ a.m. (vs. 10.3 ± 0.9 and 11.3 ± 0.6 mmol/1, p = 0.0003 and p < 0.0001, respectively, with placebo). Thereafter, starting 1 h after breakfast, no significant differences in plasma glucose, insulin, C-peptide or glucagon profiles were found between experiments with GLP-1 (7-36 amide) and placebo. Average plasma glucose concentrations over the whole 24 h period were reduced by 18% by GLP-1 administered overnight. In conclusion, (1) overnight GLP-1 (7 — 36 amide) normalizes fasting plasma glucose, but (2) has no sustained effect on meal-induced glucose, insulin or glucagon concentrations once its administration has been stopped. (3) Normalization of fasting plasma glucose alone does not improve daytime metabolic control in NIDDM patients on oral agents.

Key words

GLP-1 (7–36 amide) - incretin - insulin - glucagon - pharmacokinetics