Antidiabetic Actions of Endogenous and Exogenous GLP-1 in Type 1 Diabetic Patients With and Without Residual β-Cell Function
- 1Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark
- 2Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Denmark
- Corresponding author: Urd Kielgast, .
OBJECTIVE To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function.
RESEARCH DESIGN AND METHODS Eight type 1 diabetic patients with (+), eight without (−) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9–39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact GIP, free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured.
RESULTS Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In type 1 diabetic+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In type 1 diabetic− patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in type 1 diabetic+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in type 1 diabetic+ and type 1 diabetic− patients. The insulinogenic index (the ratio of insulin to glucose) decreased in type 1 diabetic+ patients during blockade of endogenous GLP-1 receptor action.
CONCLUSIONS Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.
- Received December 28, 2010.
- Accepted February 17, 2011.
- © 2011 by the American Diabetes Association.
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