title: TNF-alpha levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Voordouw
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: Van Weissenbruch
authors.forename: John S
authors.initials: JS
authors.lastname: Yudkin
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000886:Anthropometry; D002196:Capillaries / Q000502:physiology; D002648:Child; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018715:Microscopy, Video; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D012867:Skin / Q000098:blood supply*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha