Plasma levels of tumor necrosis factor-alpha (TNF-alpha] are essentially dependent on visceral fat amount in type 2 diabetic patients

TNF-alpha is considered as one of the potential determinants of insulin res istance. However several data suggest that TNF-alpha expression itself, cou ld be modulated by the degree of adiposity and/or plasma insulin levels. To clarify the determinants of plasma TNF-alpha levels in type 2 diabetes mel litus, we studied the impact of intensive insulin treatment on plasma TNF-a lpha levels in 16 type 2 diabetic subjects with failure to oral antidiabeti c medication (HbA1c: 10.8 +/- 1.2 %). Furthermore, we analyzed the relation ship between plasma TNF-alpha levels and total or regional body fat measure ments using anthropometry, bienergetic absorptiometry and computed tomograp hy in a cohort of 33 caucasian obese type 2 diabetic subjects (BMI: 32.2 +/ - 4.4 kg/m(2)). The plasma TNF-alpha level was neither affected by plasma g lucose level variations nor intensive insulin treatment despite a 37 % decr ease in daily insulin needs at the end of insulin therapy (total duration: 11.5 +/- 2.0 days). The plasma TNF-alpha level was similar in men and women and unrelated to age, fasting glycemia or HbA1c. A relationship was highli ghted with BMI (r = 0.39, p < 0.02), but not with total fat mass. This rela tionship was only dependent on the intra-abdominal fat mass amount as asses sed by the waist-to-hip circumference ratio (r = 0.52, p < 0.01) and the vi sceral adipose tissue area (r = 0.56, p < 0.01). These results show that pl asma TNF-alpha levels are essentially dependent on visceral fat amount, thu s suggesting that TNF-alpha could be one of the factors mediating insulin r esistance and cardiovascular risk in obese type 2 diabetic patients.