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Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of glucocorticoids in men with the metabolic syndrome? A randomized controlled trial.
- Source :
-
European Journal of Endocrinology . Mar2014, Vol. 170 Issue 3, p429-439. 11p. - Publication Year :
- 2014
-
Abstract
- Objective: Anti-inflammatory glucocorticoid (GC) therapy often induces hyperglycemia due to insulin resistance and islet-cell dysfunction. Incretin-based therapies may preserve glucose tolerance and pancreatic islet-cell function. In this study, we hypothesized that concomitant administration of the dipeptidyl peptidase-4 inhibitor sitagliptin and prednisolone in men at high risk to develop type 2 diabetes could protect against the GC-induced diabetogenic effects. Design and methods: Men with the metabolic syndrome but without diabetes received prednisolone 30 mg once daily plus sitagliptin 100 mg once daily (n=14), prednisolone (n=12) or sitagliptin alone (n=14) or placebo (n=12) for 14 days in a double-blind 2×2 randomized-controlled study. Glucose, insulin, C-peptide, and glucagon were measured in the fasted state and following a standardized mixed-meal test. β-cell function parameters were assessed both from a hyperglycemic-arginine clamp procedure and from the meal test. Insulin sensitivity (M-value) was measured by euglycemic clamp. Results: Prednisolone increased postprandial area under the curve (AUC)-glucose by 17% (P<0.001 vs placebo) and postprandial AUC-glucagon by 50% (P<0.001). Prednisolone reduced 1st and 2nd phase glucose-stimulated-and combined hyperglycemia-arginine-stimulated C-peptide secretion (all P≤0.001). When sitagliptin was added, both clamp-measured β-cell function (P=NS for 1st and 2nd phase vs placebo) and postprandial hyperglucagonemia (P=NS vs placebo) remained unaffected. However, administration of sitagliptin could not prevent prednisolone-induced increment in postprandial glucose concentrations (P<0.001 vs placebo). M-value was not altered by any treatment. Conclusion: Fourteen-day treatment with high-dose prednisolone impaired postprandial glucose metabolism in subjects with the metabolic syndrome. Concomitant treatment with sitagliptin improved various aspects of pancreatic islet-cell function, but did not prevent deterioration of glucose tolerance by GC treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08044643
- Volume :
- 170
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- European Journal of Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 94957736
- Full Text :
- https://doi.org/10.1530/EJE-13-0610