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

  1. Iris Shai, RD, PHD123,
  2. Matthias B. Schulze, DRPH1,
  3. JoAnn E. Manson, MD, DRPH245,
  4. Kathryn M. Rexrode, MD, MPH5,
  5. Meir J. Stampfer, MD, DRPH124,
  6. Christos Mantzoros, MD, SCD6 and
  7. Frank B. Hu, MD, PHD124
  1. 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  2. 2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  3. 3S. Daniel Abraham International Center for Health and Nutrition, Department of Epidemiology, Ben-Gurion University, Beer-Sheva, Israel
  4. 4Channing Laboratory, Department of Medicine, Brigham Women Hospital and Harvard Medical School, Boston, Massachusetts
  5. 5Division of Preventive Medicine, Department of Medicine, Brigham Women Hospital and Harvard Medical School, Boston, Massachusetts
  6. 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  1. Address correspondence and reprint requests to Iris Shai, RD, PhD, Harvard School of Public Health, Department of Epidemiology, 677 Huntington Ave., Boston, MA 02115. E-mail: ishai{at}hsph.harvard.edu or irish{at}bgu.ac.il

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 HbA1c (>7%), compared with diabetic subjects with lower levels (25% vs. 7%, P < 0.0001). Diabetic subjects with only higher sTNF-RII or HbA1c had similar (16–17%) risk. In a multivariate model, diabetic subjects with higher levels of both sTNF-RII and HbA1c 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.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted March 7, 2005.
    • Received December 20, 2004.
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  1. doi: 10.2337/diacare.28.6.1376 Diabetes Care June 2005 vol. 28 no. 6 1376-1382
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