Relation Between Plasma Tumor Necrosis Factor- and Insulin Sensitivity in Elderly Men With Non–Insulin-Dependent Diabetes Mellitus

From the King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm (J.N., S.J., A.N.), and the Department of Geriatrics, University of Uppsala, Uppsala (R.R., H.L.), Sweden.

Correspondence to Jan Nilsson, King Gustaf V Research Institute, Karolinska Hospital, 171 76 Stockholm, Sweden.

Abstract—Human obesity is associated with an increased tumor necrosis factor- (TNF-) mRNA expression in adipose tissue. TNF- decreases insulin-dependent glucose uptake by inhibiting autophosphorylation of the insulin receptor, suggesting that TNF- may play a role in insulin resistance. In this study, we analyzed plasma levels of TNF- in 40 70-year-old men with newly detected non–insulin-dependent diabetes mellitus and in 20 age-matched controls. Twenty of the patients had a moderate level of insulin resistance and 20 were severely insulin resistant. The plasma levels of TNF- were higher in patients (4.00±1.53 pg/mL in moderately insulin resistant and 4.91±1.43 pg/mL in severely insulin resistant subjects) than in controls (3.27±0.79 pg/mL, P<0.001). TNF- was significantly related to body mass index, fasting glucose levels, and serum triglyceride levels and inversely related to the high density lipoprotein cholesterol level. The finding of an association between high plasma levels of TNF- and several metabolic abnormalities characteristic for the insulin resistance syndrome suggests that TNF- may be involved in the pathogenesis of non–insulin-dependent diabetes mellitus.

Key Words: tumor necrosis factor- • diabetes • insulin resistance • triglycerides • HDL

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