Published in:
01-12-2007 | Article
Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes
Published in: Diabetologia | Issue 12/2007
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Aims/hypothesis
Clear evidence exists that TNF-α inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-α in type 2 diabetes.
Methods
We obtained blood and biopsy samples from skeletal muscle and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103).
Results
Patients with type 2 diabetes had higher plasma levels of fasting insulin (p < 0.0001) and glucose (p < 0.0001) compared with controls, but there was no difference between groups with regard to fat mass. Plasma levels of TNF-α (p = 0.0009) and soluble TNF receptor 2 (sTNFR2; p = 0.002) were elevated in diabetic patients. Insulin sensitivity was correlated with quartiles of plasma TNF-α after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O2 uptake \(
{\left( {\ifmmode\expandafter\dot\else\expandafter\.\fi{V}O_{{\text{2}}} {\text{/kg}}} \right)}
\) in the diabetes group (p < 0.05). The TNF mRNA content of adipose or muscle tissue did not differ between the groups, whereas muscle TNF-α protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-α protein in type 2 than in type 1 muscle fibres.
Conclusions/interpretation
After adjustment for multiple confounders, plasma TNF-α is associated with insulin resistance. This supports the idea that TNF-α plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-α protein levels in plasma and skeletal muscle indicate that measurement of TNF mRNA content in adipose or muscle tissue provides no information with regard to the degree of insulin resistance.