CIRCULATING TNF-ALPHA AND LEPTIN LEVELS IN OFFSPRING OF NIDDM PATIENTS DO NOT CORRELATE TO INDIVIDUAL INSULIN SENSITIVITY

Obesity plays a central role in the development of skeletal muscle ins ulin resistance. The molecular mechanism causing skeletal muscle insul in resistance in obese people is still poorly understood. It has been speculated that circulating factors derived from adipose tissue impair insulin signalling in the skeletal muscle cell. TNF-alpha and leptin, which are overproduced in fat tissue of obese insulin resistant anima l models and in obese humans, might mediate such an inhibitory effect on insulin signalling in skeletal muscle. The aim of the present study was to evaluate whether circulating TNF-alpha and leptin correlates t o the individual skeletal muscle insulin sensitivity in individuals wi th different degrees of obesity and insulin resistance. We measured ci rculating TNF-alpha and leptin values in non diabetic offsprings of NI DDM patients. 36 German and 47 Finnish subjects participated in the st udy. The GDR of each participant was determined by the euglycemic hype rinsulinemic clamp technique, a range between 1.37 to 14.01 mg/kg LBM x min was observed. Percent of desirable body weight (PDW) covered als o a wide range (87.58% to 197.06%). Although linear regression analysi s suggested a dependance between TNF-alpha and GDR (Germany group: r = -0.37, p < 0.05, Finnish group: r = -0.32, p < 0.05) and a dependance between TNF and PDW (German group: r = 0.46, p < 0.05, Finnish group: r = 0.38, p < 0.05), in multiple linear regression analysis only the correlation with PDW was significant. Leptin levels were measured from 29 German and 36 Finnish subjects and a strong association was found between leptin and PDW (German group: r = 0.55, p < 0.05, Finnish grou p: r = 0.73, p < 0.05). In contrast, leptin levels did not correlate w ith GDR and TNF-alpha. In summary, even though, in a few insulin resis tant subjects, higher circulating TNF-alpha or leptin levels with the individual insulin sensitivity can be demonstrated, the data suggest t hat the circulating pool of TNF-alpha and leptin in blood is unlikely to be a major contributing factor for obesity induced insulin resistan ce in the vast majority of individuals at high risk to develop NIDDM.