Background/Purpose: Accelerated atherosclerosis in rheumatoid arthritis (RA) is well established but the role of insulin resistance in RA pts without diabetes or metabolic syndrome remains to be determined. Therefore, the aim of our study was to investigate the prevalence of insulin resistance in RA pts with normal glycoregulation and its association with carotid intima-media thickness (IMT) and therapy exposure.

Methods: Our study population included 90 RA pts (age 52.4±9.9 yrs, 86.7% females, disease duration 9 yrs, range 4-13). We determined body mass index (BMI), waist circumference (WC), blood pressure, smoking habits, and disease activity score (mDAS28-SE). IMT was measured bilaterally, at common carotid (CCA), bifurcation (BF), and internal carotid arteries (CI). All pts were treated with disease modifying antirheumatic drugs, 65.6% were on steroids (<10 mg/day), and 27.8% were on biological therapy. IR was calculated using the updated-computer Homeostasis Model Assessment (HOMA2-IR), based on fasting plasma glucose and serum specific insulin concentrations (measured by ELISA). Insulin resistance was defined as HOMA2-IR>1.

Results: Insulin resistance was detected in 74.4% of pts with median value of 1.4 (range 1.0-2.3). Pts with insulin resistance compared to those without this condition had increased IMT (mm) at all levels of carotid arteries. CCA_max: 0.841±0.144 vs. 0.762±0.105 (p=0.018); CCA_mean 0.740±0.129 vs. 0.653±0.097, p=0.004; BF_max: 1.059±0.169 vs. 0.920±0.124, p=0.001; BF_mean: 0.908±0.141 vs. 0.782±0.126, p=0.000; CI_max: 0.678±0.085 vs. 0.620±0.121, p=0.014; CI_mean: 0.599±0.077 vs. 0.553±0.091, p=0.020. Both groups were comparable regarding RA duration and anti-inflammatory treatment including glycocorticoids. In multivariate logistic regression adjusted for age, BMI, WC, and triglycerides we found that statistical significance disappeared for CCA and CI but stil persisted for BF (e.g. for age BF_max β coef. 4.479, p=0.030; BF_mean: β coef. 6.516, p=0.017). In univariant regression analysis, we revealed predictive value of logHOMA2-IR for IMT BF_max:  β coef. 0.253, p=0.001; BF_mean: β coef. 0.178, p= 0.006; CI_max: β coef 0.097 p=0.026; while for other levels statistical significance was borderline (for CI_mean and CCA_meanp=0.052, and for CCAmax p=0.064). On the other hand we found significant association of logHOMA2-IR with disease activity: DAS28 β coef 0.034, p=0.037.

Conclusion: RA pts with insulin resistance had significantly increased carotid IMT at all evaluated levels. Significant difference persisted for carotid BF even after adjustment for well known risk factors for atherosclerosis. Significant association of insulin resistance and disease activity may indicate the important role of RA itself in the interplay of IR and atherosclerosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-insulin-resistance-in-the-development-of-premature-atherosclerosis-in-patients-with-rheumatoid-arthritis/