A prospective study of soluble tumor necrosis factor-alpha receptor II (sTNF-RII) and risk of coronary heart disease among women with type 2 diabetes.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by adipose tissue and other cells, might play a role in insulin resistance.


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-alpha 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.
Shai
Iris
I
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. ishai@hsph.harvard.edu
Schulze
Matthias B
MB
Manson
Joann E
JE
Rexrode
Kathryn M
KM
Stampfer
Meir J
MJ
Mantzoros
Christos
C
Hu
Frank B
FB
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000453:epidemiology; D008019:Life Style; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012306:Risk; D012907:Smoking; D013997:Time Factors
D015415:Biomarkers; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein