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

Abstract

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% CI 1.08–5.69; P = 0.034) for myocardial infarction (MI) and 2.02 (1.17–3.48; P = 0.003) for total CHD. 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 hyperglycemia.