1. TNF-alpha levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance
- Author
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Henriette A. Delemarre-van de Waal, Coen D.A. Stehouwer, Mirjam M. van Weissenbruch, John S Yudkin, Erik H. Serné, Jasper J. Voordouw, Richard G. IJzerman, Internal medicine, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Pediatric surgery, ACS - Microcirculation, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: CARIM School for Cardiovascular Diseases
- Subjects
Adult ,Male ,medicine.medical_specialty ,Necrosis ,medicine.medical_treatment ,Microcirculation ,Hyperaemia ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Obesity ,Child ,Skin ,Microscopy, Video ,Anthropometry ,business.industry ,Tumor Necrosis Factor-alpha ,Insulin ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,Capillaries ,Endocrinology ,Glucose Clamp Technique ,Linear Models ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,Insulin Resistance ,business ,Body mass index - Abstract
The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α 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-α 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-α 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-α 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-α and insulin sensitivity [-0.527 mg · kg-1 of body weight · min-1 per pmol/l per pg/ml TNF-α (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-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
- Published
- 2006