Objectives To compare glucose tolerance and parameters of insulin sensitivity and β-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA).
Methods Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and β-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics.
Results Glucose tolerance state, insulin sensitivity and β-cell function did not differ between the two RA populations; de novo T2DM was detected in 11% and impaired glucose metabolism in 35% of patients with RA. In patients with RA, cumulative GC dose was associated with T2DM, which seemed mostly driven by the effects of cumulative GC dose on insulin resistance; however, the association decreased when corrected for current disease activity. Patients with RA had decreased insulin sensitivity and impaired β-cell function compared with controls, and multivariate regression analyses showed a negative association between the presence of RA and insulin sensitivity.
Conclusions GC-using and GC-naive patients with RA had comparable metabolic parameters, and had decreased insulin sensitivity and β-cell function as compared with healthy controls. Although cumulative GC dose was shown to have a negative impact on glucose tolerance state and insulin sensitivity, confounding by indication remains the main challenge in this cross-sectional analysis.
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Funding This research was performed within the framework of project T1-106 of the Dutch Top Institute Pharma.
Competing interests JNH, MCvdG, DHvR, NJvdZ, DdU, WFL, JWGJ, PMJW and JWJB declared no conflicts of interest. MD disclosed advisory board membership for Abbott, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Poxel Pharma; is consultant for Astra Zeneca/BMS, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Sanofi Aventis; is on the speaker's bureau for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk; through MD the Diabetes Center, VU University Medical Center receives all fees related to the activities mentioned above, as well as research support from Amylin Pharmaceuticals, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Takeda.
Ethics approval This study was conducted with the approval of the University Medical Center Utrecht.
Provenance and peer review Not commissioned; externally peer reviewed.