title: Short-term metabolic effects of prednisone administration in healthy subjects.
abstract: OBJECTIVE
  Supraphysiologic glucocorticoid activity is well established to cause impaired glucose tolerance and insulin resistance, yet no study has evaluated dose-dependent effects of low-dose prednisone during short-term oral administration.
  
  
  METHODS
  The objective of this study was to quantify the effects of daily 10 or 25 mg prednisone administration for one week on insulin sensitivity by employing a two-step hyperinsulinemic euglycemic glucose clamp (Step 1: insulin infusion = 20 mU/m²/min; Step 2: insulin infusion = 80 mU/m²/min) in healthy, lean males. The amount of glucose infused at steady-state to maintain stable blood glucose [90 mg/dl (4.95 mmol/l)] was used to calculate several indices of insulin sensitivity.
  
  
  RESULTS
  During Step 1 of the clamp, whole body glucose disposal (M) was reduced by 35% (p = 0.003) and M/I was reduced by 29% (p = 0.025) for 25 mg prednisone compared to placebo. No appreciable effect of 10 mg prednisone was observed. During Step 2, M was reduced by 33% (p = 0.001) and 15% (p = 0.006) for 25 and 10 mg prednisone compared to placebo; and M/I ratio was reduced by 31% (p < 0.001) and 13% (p = 0.026), respectively. The insulin sensitivity index, Si, calculated as the quotient of augmentation of M/I between Step 1 and 2, was reduced by 35.3% (p < 0.01) and 23.5% (p < 0.05) for 25 and 10 mg prednisone, respectively.
  
  
  CONCLUSIONS
  Administration of relatively low pharmacological doses of prednisone for one week impaired insulin sensitivity in a dose-dependent manner in healthy males. These observed changes in insulin sensitivity are likely to be clinically relevant, especially in individuals predisposed to develop glucose intolerance.
authors.affiliation: Merck Sharp & Dohme Corporation, North Wales, PA, USA. eunkyung_kauh@merck.com
authors.forename: E A
authors.initials: EA
authors.lastname: Kauh
authors.forename: L A
authors.initials: LA
authors.lastname: Mixson
authors.forename: S
authors.initials: S
authors.lastname: Shankar
authors.forename: J
authors.initials: J
authors.lastname: McCarthy
authors.forename: V
authors.initials: V
authors.lastname: Maridakis
authors.forename: L
authors.initials: L
authors.lastname: Morrow
authors.forename: L
authors.initials: L
authors.lastname: Heinemann
authors.forename: M K
authors.initials: MK
authors.lastname: Ruddy
authors.forename: G A
authors.initials: GA
authors.lastname: Herman
authors.forename: D E
authors.initials: DE
authors.lastname: Kelley
authors.forename: M
authors.initials: M
authors.lastname: Hompesch
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D011241:Prednisone