Volume 49, Number 3, 452-458, DOI: 10.1007/s00125-005-0126-y

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European Association for the Study of Diabetes

Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

J. J. Meier, A. Gethmann, O. Götze, B. Gallwitz, J. J. Holst, W. E. Schmidt and M. A. Nauck

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Abstract

Aims/hypothesis  

Diabetic dyslipidaemia contributes to the excess morbidity and mortality in patients with type 2 diabetes. Exogenous glucagon-like peptide 1 (GLP-1) lowers postprandial glycaemia predominantly by slowing gastric emptying. Therefore, the effects of GLP-1 on postprandial lipid levels and gastric emptying were assessed.

Methods  

14 healthy male volunteers were studied with an i.v. infusion of GLP-1 (1.2 pmol kg−1 min−1) or placebo over 390 min in the fasting state. A solid test meal was served and gastric emptying was determined using a 13C-labelled sodium octanoate breath test. Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA.

Results  

GLP-1 administration lowered fasting and postprandial glycaemia (p<0.0001). Gastric emptying was delayed by GLP-1 compared with placebo (p<0.0001). During GLP-1 administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33±0.14 mmol/l in the placebo experiments (p<0.0001). In contrast, the postprandial increase in triglyceride levels was completely abolished by GLP-1 (change in triglycerides, −0.023±0.045 mmol/l; p<0.05). During GLP-1 infusion, plasma concentrations of NEFA were suppressed by 39% in the fasting state (p<0.01) and by 31±5% after meal ingestion (p<0.01).

Conclusions/interpretation  

GLP-1 improves postprandial lipidaemia, presumably as a result of delayed gastric emptying and insulin-mediated inhibition of lipolysis. Thus, by lowering both glucose and lipid concentrations, GLP-1 administration may reduce the cardiovascular risk in patients with type 2 diabetes.

Keywords  Gastric emptying - Glucagon-like peptide 1 - GLP-1 - Insulin secretion - NEFA - Triglycerides

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