A prospective study of soluble tumor necrosis factor-α receptor II (sTNF-RII) and risk of coronary heart disease among women with type 2 diabetes

OBJECTIVE - Tumor necrosis factor-α (TNF-α), a cytokine secreted by adipose tissue and other cells, might play a role in insulin resistance. RESEARCH DESIGN AND METHODS - Of 32,826 women from the Nurses' Health Study who provided blood at baseline, we followed 929 women with type 2 diabetes. During 10 years of follow-up, we documented 124 incident cases of coronary heart disease (CHD). RESULTS - After adjustment for age, smoking, BMI, and other cardiovascular risk factors, the relative risks (RRs) comparing extreme quartiles of soluble TNF-α receptor II (sTNF-RII) were 2.48 (95% Cl 1.08-5.69; P = 0.034) for myocardial infarction (MI) and 2.02 (1.17-3.48; P = 0.003) for total CHID. The probability of developing CHD over 10 years was higher among diabetic subjects with substantially higher levels of both sTNF-RII (> 75th percentile) and HbA(1c) (> 7%), compared with diabetic subjects with lower levels (25% Vs. 7%, P < 0.0001). Diabetic subjects with only higher sTNF-RII or HbA(1c) had similar (16-17%) risk. In a multivariate model, diabetic subjects with higher levels of both sTNF-RII and HbA(1c) had an RR of 3.66 (1.85-7.22 for MI and 3.03 (1.82-5.05) for total CHD, compared with those with lower levels of both biomarkers. CONCLUSIONS - increased levels of sTNF-RII were strongly associated with risk of CHD among diabetic women, independent of hypoglycemia.