Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans
- Daniël H. van Raalte, MD1,
- Renate E. van Genugten, MD1,
- Margot M.L. Linssen, MSC2,
- D. Margriet Ouwens, PHD3 and
- Michaela Diamant, MD, PHD1
- 1Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
- 2Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands
- 3The Institute of Clinical Biochemistry and Pathobiochemistry, The German Diabetes Center, Düsseldorf, Germany
- Corresponding author: Daniël H. van Raalte,
D.H.v.R. and R.E.v.G. contributed equally to this work.
OBJECTIVE Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance.
RESEARCH DESIGN AND METHODS A randomized, placebo-controlled, double-blind, crossover study in eight healthy men (age: 23.5 [20.0–28.3] years; BMI: 26.4 [24.3–28.0] kg/m2) was conducted. Participants received three therapeutic regimens for 2 consecutive days: 1) 80 mg of oral prednisolone (PRED) every day (q.d.) and intravenous (IV) EXE infusion (PRED+EXE); 2) 80 mg of oral PRED q.d. and IV saline infusion (PRED+SAL); and 3) oral placebo-PRED q.d. and intravenous saline infusion (PLB+SAL). On day 1, glucose tolerance was assessed during a meal challenge test. On day 2, participants underwent a clamp procedure to measure insulin secretion and insulin sensitivity.
RESULTS PRED+SAL treatment increased postprandial glucose levels (vs. PLB+SAL, P = 0.012), which was prevented by concomitant EXE (vs. PLB+SAL, P = NS). EXE reduced PRED-induced hyperglucagonemia during the meal challenge (P = 0.018) and decreased gastric emptying (vs. PRED+SAL, P = 0.028; vs. PLB+SAL, P = 0.046). PRED+SAL decreased first-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL, P = 0.017 and P = 0.05, respectively), whereas PRED+EXE improved first- and second-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL; P = 0.017, 0.012, and 0.093, respectively).
CONCLUSIONS The GLP-1 RA EXE prevented PRED-induced glucose intolerance and islet-cell dysfunction in healthy humans. Incretin-based therapies should be explored as a potential strategy to prevent steroid diabetes.
Clinical trial reg. no. NCT00744224, clinicaltrials.gov.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc10-1677/-/DC1.
- Received August 30, 2010.
- Accepted October 23, 2010.
- © 2011 by the American Diabetes Association.
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