title: Effects of low-dose prednisolone on hepatic and peripheral insulin sensitivity, insulin secretion, and abdominal adiposity in patients with inflammatory rheumatologic disease.
abstract: OBJECTIVE
  The metabolic effects of low-dose prednisolone and optimal management of glucocorticoid-induced diabetes are poorly characterized. The aims were to investigate the acute effects of low-dose prednisolone on carbohydrate metabolism and whether long-term low-dose prednisolone administration increases visceral adiposity, amplifying metabolic perturbations.
  
  
  METHODS
  Subjects with inflammatory rheumatologic disease without diabetes mellitus were recruited. Nine subjects (age, 59 ± 11 years) not using oral glucocorticoids were studied before and after a 7- to 10-day course of oral prednisolone 6 mg daily. Baseline data were compared with 12 subjects (age, 61 ± 8 years) using continuous long-term prednisolone (6.3 ± 2.2 mg/day). Basal endogenous glucose production (EGP) was estimated by 6,6-(2)H2 glucose infusion, insulin sensitivity was estimated by two-step hyperinsulinemic-euglycemic clamp, insulin secretion was estimated by intravenous glucose tolerance test, and adipose tissue areas were estimated by computed tomography.
  
  
  RESULTS
  Prednisolone acutely increased basal EGP (2.44 ± 0.46 to 2.65 ± 0.35 mg/min/kg; P = 0.05) and reduced insulin suppression of EGP (79 ± 7 to 67 ± 14%; P = 0.03), peripheral glucose disposal (8.2 ± 2.4 to 7.0 ± 1.6 mg/kg/min; P = 0.01), and first-phase (5.9 ± 2.0 to 3.9 ± 1.6 mU/mmol; P = 0.01) and second-phase (4.6 ± 1.7 to 3.6 ± 1.4 mU/mmol; P = 0.02) insulin secretion. Long-term prednisolone users had attenuated insulin suppression of EGP (66 ± 14 vs. 79 ± 7%; P = 0.03) and nonoxidative glucose disposal (44 ± 24 vs. 62 ± 8%; P = 0.02) compared with nonglucocorticoid users, whereas basal EGP, insulin secretion, and adipose tissue areas were not significantly different.
  
  
  CONCLUSIONS
  Low-dose prednisolone acutely perturbs all aspects of carbohydrate metabolism. Long-term low-dose prednisolone induces hepatic insulin resistance and reduces peripheral nonoxidative glucose disposal. We conclude that hepatic and peripheral insulin sensitivity should be targeted by glucose-lowering therapy for glucocorticoid-induced diabetes.
authors.affiliation: Faculty of Health Sciences, Flinders University, Adelaide, Australia. carolynpetersons@yahoo.com.au
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Petersons
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Mangelsdorf
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Jenkins
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Smith
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.forename: Campbell H
authors.initials: CH
authors.lastname: Thompson
authors.forename: Morton G
authors.initials: MG
authors.lastname: Burt
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D050260:Carbohydrate Metabolism / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D012213:Rheumatic Fever
chemical_list: D000893:Anti-Inflammatory Agents; D011239:Prednisolone; D005947:Glucose