Serum Levels of Tumor Necrosis Factor-α Are Increased in Obese Patients with Noninsulin-Dependent Diabetes Mellitus1

To clarify the significance of the serum levels of tumor necrosis factor-α (TNF-α) in the mechanism of insulin resistance, we studied 12 obese patients with noninsulin-dependent diabetes mellitus (NIDDM). We evaluated the relationship of TNF-α levels with the visceral, subcutaneous, and total fat areas measured by computed tomography (CT), and with insulin resistance evaluated by the glucose infusion rate (GIR) observed during an euglycemic hyperinsulinemic clamp study. Controls consisted of 12 normal subjects and 12 nonobese patients with NIDDM. TNF-α levels were measured using a high sensitivity enzyme-linked immunosorbent assay. Following admission, all patients with NIDDM participated in a 4-week program of diet and exercise. After this treatment, we evaluated the relationship of the serum levels of TNF-α with the area of body fat, the GIR, and the resultant change in the TNF-α level. Serum levels of TNF-α in the obese patients with NIDDM significantly exceeded those observed in normal subjects (P < 0...