CLINICAL STUDY Plasma adiponectin concentration and tumor necrosis factor-a system activity in lean non-diabetic offspring of type 2 diabetic subjects Irina Kowalska,Marek Stra˛czkowski, Agnieszka Nikolajuk, Agnieszka Krukowska, Ida Kinalska and Maria Go ´rska Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15276 Bialystok, ul. M C Sklodowskiej 24a, Poland (Correspondence should be addressed to I Kowalska; Email:irinak@poczta.onet.pl) Abstract Objective: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin’s role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-a system. Research design and methods: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glu- cose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-a, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated. Results: The insulin sensitivity index, normalized for fat-free mass (M ffm ) and adiponectin concen- trations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P ¼ 0.0046 and P ¼ 0.00 058 respectively). TNF-a and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P ¼ 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r ¼ 0.34; P ¼ 0.020) and to HDL-cholesterol (r ¼ 0.29, P ¼ 0.047) and was inversely related to sTNFR2 (r ¼ 2 0.33, P ¼ 0.027). Conclusions: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects. European Journal of Endocrinology 154 319–324 Introduction Adiponectin, a 30 kDa protein, is synthesized exclu- sively by adipose tissue (1, 2). There is growing evi- dence that the function of adiponectin is closely related to the pathogenesis of insulin resistance (3, 4). It is well accepted that insulin resistance plays an important role in the etiology of several contemporary diseases including obesity, coronary heart disease, hypertension and type 2 diabetes mellitus (5–8). How- ever, impaired insulin action was already observed in healthy normoglycemic subjects with a strong family history of type 2 diabetes (9). Pratipanawatr et al. showed that insulin-stimulated receptor substrate-1 activation was impaired in skeletal muscle of offspring of type 2 diabetic subjects (9). In the last few years, great interest has been directed to the secretory protein of white adipose tissue, known as adiponectin or adipocyte complement related protein (ACRP30), AdipoQ or adipose most abundant gene transcript 1 (apM1). The serum concentration of adipo- nectin is relatively high. As mentioned earlier, adipo- nectin is synthesized exclusively by adipose tissue and decreased serum concentrations of adiponectin corre- late with insulin resistance, which has been observed in experimental (10) and epidemiological studies (11, 12). Low adiponectin concentrations have been observed in human obesity (13), type 2 diabetes melli- tus (12), coronary heart disease (14) and hypertension (15). In patients with anorexia nervosa, the concen- tration of adiponectin was significantly higher in spite of a marked deficiency of adipose tissue (16). In exper- imental studies, recombinant adiponectin suppressed the development of atherosclerosis (17) and improved insulin sensitivity, mainly by increasing fatty acids oxi- dation and inhibition of hepatic glucose production European Journal of Endocrinology (2006) 154 319–324 ISSN 0804-4643 q 2006 Society of the European Journal of Endocrinology DOI: 10.1530/eje.1.02084 Online version via www.eje-online.org