Background Rheumatoid arthritis (RA) and atherosclerosis are both considered inflammatory diseases who share several common pathogenic mechanisms¹. In general population, insulin resistance (IR) is an established risk factor for cardiovascular diseases (CVD)². Chronic inflammation and endothelial activation play a pivotal role in development of IR³. Hence IR and premature atherosclerosis may be implicated as major co-morbidities in enhancing the CV risk in RA.

Objectives The study aim was to elucidate the relationship between inflammatory markers, IR state and atherosclerotic indices in RA patients.

Methods Forty consecutive RA patients (20 early RA with disease duration<1year and 20 late RA with disease duration>5years) fulfilling the selection criteria (ACR '87; excluded confounding variables) were recruited from the OPD of Rheumatology Department, IPGME&R, Kolkata. Volunteers meeting selection criteria were recruited as healthy controls (HC). The demographic features of both patients and controls and clinical features of patients were documented. Composite Disease Activity Score (DAS28) was calculated using SJC28, TJC28, VAS and Westergren erythrocyte sedimentation rate (ESR).

Overnight fasting serum samples were obtained from early RA, late RA and HC. Lipid levels and glucose were determined with biochemical kits. High sensitivity C-reactive protein (hsCRP) was measured using turbidometric technique. Insulin levels were measured by ELISA. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was calculated using glucose and insulin values. Atherosclerotic indices like mean carotid intima-media thickness (cIMT) and endothelial dependent flow mediated vasodilatation (ED-FMD) were measured using HRUS.

One way ANOVA with post hoc tests and linear regression analyses were used. All statistical analyses were performed using GraphPad Prism software v 5.0.

Results Mean disease duration of Late RA patients was 9.6±3.3 yrs and that of early RA was 0.46±0.36 yrs. There were no significant differences in the demographic variables and lipid profile among the three groups. Unlike ESR, hsCRP levels were significantly lower in the late RA patients as compared to that of the early RA (p=0.04). DAS 28 did not show significant difference among the two patients group. HOMA-IR was significantly higher in the Late RA group [1.04 (0.3–7.04)] when compared to early RA [0.59 (0.007–1.8)] and HC [0.42 (0.07–1.5)]. Mean cIMT was significantly higher in both the early RA patients (0.49±0.08mm) and late RA patients group (0.51±0.09mm) than in the HC (0.42±0.07 mm). In early RA patients median FMD% was significantly lower (6.71±4.32) as compared to late RA patients (11.75±7.67) and HC (12.23±4.6). Regression analysis showed significant associations of HOMA-IR with Mean cIMT, DAS 28 and hsCRP (figure 1) and also with age, disease duration, ESR and trends in association with FMD% values for late RA group.

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Conclusions Underlying inflammation prevailing in RA patients probably leads to stimulation of an insulin resistant state which further enhances the already significant atherosclerotic milieu in these patients.

References

1. Snow MH, et al. Curr. Opin. Rheumatol. 2005; 17: 234–241.

2. Grundy SM. Endocrinol Metab Clin North Am. 2004; 33:267–82.

3. Shoelson SE, et al. J Clin Invest. 2006; 116: 1793–1801.

Acknowledgements The presenting author is grateful to the INDIAN COUNCIL OF MEDICAL RESEARCH (ICMR) for providing the fellowship grant.

Disclosure of Interest None declared