Rheumatoid factor mediates excess serum lipoprotein(a) for independent association with type 2 diabetes in men

OBJECTIVE The potential association of rheumatoid factor (RF) and lipoprotein (Lp)(a) levels, as well as with the likelihood of type 2 diabetes and hypertension, needs exploring. METHODS Cross-sectional associations were sought in this unselected and population-based 1539-adult cohort (age 58.8±10.6 years). RF was assayed nephelometrically. Multiple logistic regression analyses were used for covariates of RF positivity and for the latter's association with diabetes and hypertension. RESULTS RF-positive individuals were older, fewer current smokers, had significantly lower fasting triglycerides (by 13%), higher fibrinogen, and tended to higher sex hormone-binding globulin (SHBG) levels. Whereas, women had a similar risk profile irrespective of RF status, RF-positive men had significantly higher Lp(a). In contrast to Lp(a) being positively correlated with SHBG in RF-negative subjects (r=0.08; p=0.007), an inverse correlation existed in seropositive individuals (r=-0.32, p=0.011), suggesting the interplay of an immune complex. In regression analyses, RF positivity was associated with Lp(a) in men but not in women, [OR 1.53 (1.19; 1.96)], independent of age, SHBG, and C-reactive protein (CRP). RF positivity was further associated with diabetes [OR 1.98 (95% CI 1.11; 3.52)] in the whole sample, additively to waist circumference and CRP, major determinants of diabetes. RF-positive subjects were not significantly associated independently with hypertension. CONCLUSION Autoimmune activation linked to Lp(a) is mediated by the autoantibody RF in contributing to the development of type 2 diabetes.