title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Diabetes Center.
authors.forename: Renate E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: Marcel H
authors.initials: MH
authors.lastname: Muskiet
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005215:Fasting; D005938:Glucocorticoids; D018149:Glucose Intolerance / Q000517:prevention & control; D006801:Humans; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology; D011239:Prednisolone / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005938:Glucocorticoids; D011719:Pyrazines; D014230:Triazoles; D011239:Prednisolone; D000068900:Sitagliptin Phosphate