title: Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction.
abstract: OBJECTIVE
  To investigate the dose-related effects of glucocorticoid treatment on glucose tolerance, beta cell function, and insulin sensitivity in patients with early active rheumatoid arthritis (RA).
  
  
  METHODS
  A randomized, controlled, single-blind trial was conducted in 41 patients with early active RA. At the beginning of the trial patients had not been treated for their RA, and were randomized to begin treatment with prednisolone at 60 mg/day or 30 mg/day. Before and at the end of 1 week of treatment, a frequently sampled oral glucose tolerance test was performed. The glucose area under the curve (AUC(G) ) was calculated. In addition, beta cell function and insulin sensitivity parameters were computed.
  
  
  RESULTS
  Patients (mean ± SD age 55.5 ± 14.8 years and 54.2 ± 12.6 years in the prednisone 60 mg/day and prednisone 30 mg/day groups, respectively; body mass index 24.5 ± 4.1 kg/m(2)  and 25.4 ± 4.2 kg/m(2) , respectively) had active disease at baseline (mean ± SD Disease Activity Score in 44 joints 4.1 ± 0.7 and 4.0 ± 0.8, respectively; median C-reactive protein [CRP] level 14 mg/liter [interquartile range 6-34] and 19 mg/liter [interquartile range 3-39], respectively). In addition, 56% of the patients had impaired glucose tolerance at baseline, and 7% were found to have previously unrecognized type 2 diabetes mellitus (DM). Associations of the AUC(G)  with erythrocyte sedimentation rate (β = 2.430 [95% confidence interval 0.179-4.681], P = 0.04) and with CRP level (β = 2.358 [95% confidence interval 0.210-4.506], P = 0.03) were demonstrated. Treatment with prednisolone at both dosages reduced CRP levels significantly. The incidence of type 2 DM increased to 24% (P < 0.001) (evenly distributed across the groups). The mean AUC(G)  did not change in either treatment arm. Beta cell function improved during prednisone treatment at 60 mg/day (P = 0.02) and at 30 mg/day (P = 0.04). Disease duration was associated with changes in the AUC(G)  (β = 3.626 [95% confidence interval 1.077-6.174], P = 0.007) and with deterioration of the glucose state (odds ratio 1.068 [95% confidence interval 1.017-1.122], P = 0.009).
  
  
  CONCLUSIONS
  In this study, short-term treatment with prednisolone 60 mg or 30 mg per day improved disease activity without deterioration of glucose tolerance in patients with active RA. However, due to individual differences, monitoring is recommended.
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: den Uyl
authors.forename: Daniel H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Jos N
authors.initials: JN
authors.lastname: Hoes
authors.forename: Ben A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D042241:Early Diagnosis; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006304:Health Status; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects* / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D011239:Prednisolone