CIRCULATING TUMOR-NECROSIS-FACTOR-ALPHA IS ELEVATED IN MALE BUT NOT IN FEMALE-PATIENTS WITH TYPE-II DIABETES-MELLITUS

The cytokine tumor necrosis factor alpha (TNF alpha) was proposed to m ediate obesity related insulin resistance upon production in fat cells and to participate in tissue remodelling leading to vascular complica tions upon being released by macrophages. To assess its putative role in diabetes we determined plasma levels of TNF alpha in 105 adult huma ns. Male nondiabetic subjects had significantly lower TNF alpha levels than female controls (4.4 +/- 0.3, n = 17 vs. 6.6 +/- 1.0 pg/ml, n = 13; p = 0.049). Men with NIDDM had elevated TNF alpha (6.7 +/- 0.6 pg/ ml, n = 34) compared to nondiabetic subjects (4.4 +/- 0.3 pg/ml, n = 1 7; p = 0.012). Such a difference was not apparent in women. Levels of TNF alpha were correlated with serum triglyceride levels in male contr ols (r(2) = 0.64; p = 0.007) but not in NIDDM. Neither body mass index nor glycosylated hemoglobin correlated with TNF alpha in any of the g roups. The presence of retinopathy (p = 0.046) but not of neuropathy o r nephropathy or macroangiopathy was associated with significantly ele vated plasma TNF alpha. We conclude that plasma levels of TNF alpha ar e sex-dependent and that increased TNF alpha occurs in male but not fe male NIDDM and may participate in the development of diabetic complica tions.