Insulin resistance is an independent risk factor for atherosclerosis in rheumatoid arthritis

The objective of this study was to investigate the relationship between insulin resistance (IR) and subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Carotid artery intima media thickness (IMT), using ultrasound evaluation, and other clinical and laboratory variables were investigated in 45 RA outpatients and in 48 controls with soft tissue disorders. IR was assayed by homeostasis model assessment (HOMA2) and metabolic syndrome by National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. Insulin resistance, as defined by HOMA2-IR>1, was seen in 40 (88.9%) RA patients and in three (6.2%) controls (p<0.001). No significant difference was detected in the prevalence of metabolic syndrome. The median IMT was greater in RA patients (0.76 mm; interquartile range [IQR] 0.65, 0.85) than in the controls (0.66 mm; IQR 0.60, 0.72) (p<0.001). Dividing the RA patients according to the cut-off IMT value (0.72 mm), a difference was detected in both systolic (p=0.04) and diastolic blood pressure (p=0.02), disease activity score (DAS28) (p=0.008), HOMA2-IR (p<0.001) and cumulative oral steroid dose (p=0.001). Moreover, the frequency of cases with increased IMT was higher in glucocorticoid users than in non-users (21/23 vs. 9/22, respectively) (p<0.001). Spearman's rho correlation showed a significant positive relationship between IMT and HOMA2-IR (p<0.001). Multivariate stepwise analysis selected HOMA2-IR plus diastolic BP plus glucocorticoid exposure as the best predictive model for subclinical atherosclerosis (R2c=0.577, F=21, p<0.001). In conclusion, this study showed a significantly higher prevalence of IR in RA patients and pointed out a significant association between IR and subclinical atherosclerosis. This relationship may be driven primarily by exposure to steroid therapy.