TNF-alpha levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance

The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.