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

Third Department of Internal Medicine (A.K., Y.S., K.I., M.F., K.T., H.G., K.N., Y.Y.) and Department of Radiology (S.M.), Mie University School of Medicine; Department of Internal Medicine (K.M., Y.T.), Yamada Red Cross Hospital, Mie, Japan

Address correspondence and requests for reprints to: Akira Katsuki, M.D., Third Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514, Japan.

To clarify the significance of the serum levels of tumor necrosis factor- (TNF-) in the mechanism of insulin resistance, we studied 12 obese patients with noninsulin-dependent diabetes mellitus (NIDDM). We evaluated the relationship of TNF- 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- 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- with the area of body fat, the GIR, and the resultant change in the TNF- level.

Serum levels of TNF- in the obese patients with NIDDM significantly exceeded those observed in normal subjects (P < 0.01) or in the nonobese patients with NIDDM (P < 0.01). Serum levels of TNF- in obese NIDDM patients showed a significant positive correlation with the area of visceral fat before (r = 0.662, P < 0.03) and after (r = 0.508, P < 0.05) the treatment; similar correlation was observed in all patients with NIDDM before (r = 0.537, P < 0.02) and after (r = 0.430, P < 0.05) the treatment. Serum levels of TNF- in obese NIDDM patients showed a significant negative correlation with GIR after the treatment (r = -0.595, P < 0.05). Serum levels of TNF- were significantly reduced in the obese patients with NIDDM after the treatment (P < 0.01), while those in the nonobese NIDDM patients were unchanged.

These results suggest that serum TNF- levels may play an important role in mechanism of insulin resistance associated with obesity.

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