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

Abstract

To clarify the significance of the serum levels of tumor necrosis factor-alpha (TNF-alpha) in the mechanism of insulin resistance, we studied 12 obese patients with noninsulin-dependent diabetes mellitus (NIDDM). We evaluated the relationship of TNF-alpha 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-alpha 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-alpha with the area of body fat, the GIR, and the resultant change in the TNF-alpha level. Serum levels of TNF-alpha 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-alpha 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-alpha in obese NIDDM patients showed a significant negative correlation with GIR after the treatment (r = -0.595, P < 0.05). Serum levels of TNF-alpha 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-alpha levels may play an important role in mechanism of insulin resistance associated with obesity.

Hypogonadotrophic Hypogonadism in Type 2 Diabetes, Obesity and the Metabolic Syndrome

“…Both obesity and diabetes have been shown to be associated with oxidative stress [75][76][77][78] and inflammation [79][80][81][82][83]. The concentration of pro-inflammatory cytokines including TNF is elevated in T2D [81] and may contribute to HH in this condition.…”

Relationship between Serum TNF Activity and Insulin Resistance in Dairy Cows Affected with Naturally Occurring Fatty Liver.

“…Recently, in animal models of obesity and insulin-resistant diabetes mellitus, it has been reported that tumor necrosis factor (TNF)-α induced insulin-resistance [8,13]. Insulin resistance was detected also in hyperketomic cows with fatty liver and abomasal displacement [4,15].…”

“…a), b), c) Means with different superscripts within the same row in each group with fatty liver are significantly different (p<0.05). in nonobese patients with NIDDM [8]. TNF-α is overproduced in adipose tissue, where it has direct autocrine or paracrine effects via local receptors.…”

“…BCS is an assessment of the amount of subcutaneous adipose tissue and reflects body nutrient reserves in cattle [2]. In obese NIDDM patients, serum TNF levels showed a positive correlation with the area of visceral fat [8]. An alteration in the metabolism of visceral fat tissue may be a primary causative response for the induction of bovine fatty liver.…”

Enhanced spontaneous and induced secretion of the proinflammatory cytokine TNF-alpha by monocytes-macrophages from the blood of the patients presenting with type 2 diabetes mellitus

“…Повышение уровня ФНО-α в крови больных СД2 хорошо известно [9][10][11], однако в доступной литературе нам не удалось найти исследований, доказывающих явную провос-палительную активацию макрофагов у пациентов с СД2. Обладая способностью индуцировать апоптоз, ФНО-α вызывает генерализацию в клеточной мем-бране активных форм кислорода -супероксид-ра-дикалов, а также оксида азота, усугубляя тем самым окислительный стресс и эндотелиальную дисфунк-цию.…”