Background/Purpose: Increased insulin resistance and impaired β-cell function have been demonstrated in rheumatoid arthritis (RA). The aim of the study was to analyze the association of these metabolic disturbances with glucocorticoid (GC) therapy.

Methods: The study population included 127 non-diabetic subjects: 90 RA pts (mean age 52.4±9.9 yrs, disease duration 9 yrs, range 4-13) and 37 matched controls (mean age 49.0±7.5 yrs). All pts were on disease modifying anti-rheumatic drugs (methotrexate in 93.3%), biologic therapy in 27.8%, and GC in 65.6%, none on GC>10 mg/day (median dose 5 mg/day, range 5-10, during 4 yrs (range 2-6 yrs), cumulative GC dose was 9.1 g (5.5-16.4 g). Clinical work-up included determination of the body mass index (BMI), waist circumference (WC), blood pressure (BP), disease activity (mDAS28-SE), inflammation markers, lipids, glucose, specific insulin, and C peptide. The updated-computer Homeostasis Model Assessment was used to calculate insulin resistance (HOMA2-IR) and β-cell function (HOMA2-%B). HOMA2-IR>1 was defined as increased insulin resistance. Lack of compensatory rise of HOMA2-%B implied impaired β-cell function.

Results: Increased insulin resistance (logHOMA2-IR>1) was detected in 74.4% of RA pts and in 54.2% of controls, p=0.025. RA pts had also higher values of logHOMA2-IR than controls 1.4 (range 1.0-2.3) vs. 1.2 (range 0.8-1.4); p=0.008; which was followed with impaired β cell function: HOMA2-%B 148 (116-190) vs.141 (114-158) p=0.186. Univariate regression revealed association of logHOMA2-IR with all insulin resistance risk factors: age, BMI, WC, BP, and triglycerides, while multivariate analysis demonstrated that beside BMI, and triglycerides, daily dose of GC was an independent risk factor for logHOMA2-IR (β 0.191, 95% CI 0.020-0.361, p=0.029).  On the other hand, statistical difference was not found for duration of GC therapy and cumulative GC dose. Analyzing patients with and without GC therapy statistical difference was not found regarding any parameters of glucose metabolism, as well as all classic insulin resistance risk factors (Table 1). In comparison with controls, higher insulin resistance was found for RA pts with GC therapy, which was not followed with differences in B cell function. Patients without GC therapy also had higher insulin resistance, but the statistical significance was borderline. Both RA groups had significantly higher number of subjects with increased insulin resistance than controls.

Conclusion: There was no significant difference in insulin resistance between RA pts with and without GC therapy. Daily dose has more significant influence than duration of GC therapy and cumulative GC dose but this therapy does not play a principal role in increased insulin resistance in RA pts.