Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients

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Abstract
The relationship between basal serum tumor necrosis factor alpha (TNFα) levels and peripheral tissue (muscle) sensitivity to insulin was examined in 63 subjects with normal glucose tolerance (NGT), 18 subjects with impaired glucose tolerance (IGT), and 123 patients with type 2 diabetes mellitus (T2DM). The BMI was similar in NGT (28.8±0.7 kg/m2), IGT (31.1±1.0), and T2DM (30.0±0.4) groups. The fasting serum TNFα concentration in T2DM (4.4±0.2 pg/ml) was significantly higher than in NGT (3.1±0.2) and IGT (3.4±0.2; both PP2 min euglycemic insulin clamp in combination with 3H-glucose) was reduced in T2DM (102±3 mg/m2 min) compared with NGT (177±10) and IGT (151±14; both Pr=−0.47, Pr=0.32, P=0.004) and FPI (r=0.32, P=0.004) in NGT plus IGT. No correlation was observed between serum TNFα and Rd (r=−0.02), FPG (r=0.15), or FPI (r=0.15) in T2DM. In stepwise multiple regression analysis using age, sex, BMI, FPG, FPI and serum TNFα concentration as independent variables, only BMI and serum TNFα concentration were significant and independent predictors of Rd (r2=0.29, Pr2=0.13, P<0.0001) in T2DM. These results suggest that: (i) an increase in circulating TNFα concentration is associated with peripheral insulin resistance and increased plasma glucose and insulin levels prior to the onset of type 2 diabetes; and (ii) the further deterioration in peripheral insulin resistance in T2DM (compared with NGT and IGT) is unrelated to the increase in serum TNFα concentration.