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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.

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.

journal_name

Eur J Endocrinol

journal_title

European journal of endocrinology

authors

van Genugten RE,van Raalte DH,Muskiet MH,Heymans MW,Pouwels PJ,Ouwens DM,Mari A,Diamant M

doi

10.1530/EJE-13-0610

subject

Has Abstract

pub_date

2014-02-04 00:00:00

pages

429-39

issue

eissn

0804-4643

issn

1479-683X

pii

EJE-13-0610

journal_volume

170

pub_type

杂志文章,随机对照试验

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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.