title: Glucagon-like peptide-1 receptor agonist treatment prevents glucocorticoid-induced glucose intolerance and islet-cell dysfunction in humans.
abstract: 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.
  
  
  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/m(2)) 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.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands. d.vanraalte@vumc.nl
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: Renate E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: Margot M L
authors.initials: MM
authors.lastname: Linssen
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D005938:Glucocorticoids / Q000009:adverse effects; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D006946:Hyperinsulinism / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011241:Prednisone / Q000009:adverse effects*; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D011241:Prednisone