Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome.

The metabolic syndrome mostly represented by obesity and hyperinsulinaemia connected with insulin resistance, presents the main mechanism in the pathogenesis of cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including leptin) and factors related to insulin resistance in groups of both normal and non-diabetic hyperlipemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. Two groups of patients (20 men, 20 women) with hypertriglyceridemia were compared with 30 individuals (10 men, 20 women) with normal serum triacylglycerols. Fasting serum leptin concentration, lipid parameters (triacylglycerols, HDL cholesterol, LDL cholesterol) and BMI were measured and compared with changes in insulin parameters influencing insulin resistance (HOMA IR, insulin, intact proinsulin, C-peptide). Statistical analysis was performed using SAS/STAT software including unpaired Student's t-test, Kolmogorov-Smirnov's test, Spearman's rank-order correlation and multiple regression analysis. In men, the insulin sensitivity correlates with leptin only. In women insulin sensitivity is markedly influenced by a complex of factors: leptin and lipid parameters. Increased insulin resistance in men is followed mainly by the increased correlations between leptin, HOMA IR and insulin parameters. In women correlations between leptin, HOMA IR and insulin parameters were smaller, but the inverse correlation with HDL cholesterol was stronger. In postmenopausal women and also in men, serum leptin concentration contributes to insulin resistance. However in women the effect of increase in serum triacylglycerols in contribution of insulin resistance seems to be more dominant.

TNF-alpha in the development of insulin resistance and other disorders in metabolic syndrome.

Insulin resistance and obesity are very frequent disorders and are described as the dominant risk factors for cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including TNF-alpha) and factors related to insulin resistance in groups of both normal and hyperlipidemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. The study was carried out on 70 out-patients of the Metabolic Center. From these, 40 patients (20 men and 20 women) were selected with mild hyperlipidemia. Two other groups (10 men and 20 women) with approximately normal serum lipids parameters were taken as "controls". In hyperlipidemic women the mean serum concentration of the TNF-alpha was no different from that in the control group in spite of the fact that values of HOMA IR, insulin, proinsulin and lipid parameters increased significantly. In hyperlipidemic men we have found the decrease in TNF-alpha in comparison with the control group. In all four groups the statistical analysis showed correlations between metabolic parameters (including TNF-alpha) and parameters related to insulin resistance. Also differences in relation to the gender have been found. Multiple regression analysis demonstrated the important role of TNF-alpha in the regulation of both the insulin resistance and in the secretion of insulin in women. In men, BMI and HDL-cholesterol played a dominant role, while the role of TNF-alpha seemed to be minimal.

Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects.

BACKGROUND: The increase in the prevalence of insulin resistance-related metabolic syndrome, a disorder that greatly increases the risk of diabetes, heart attack and stroke, is alarming. One of the most frequent and early symptoms of metabolic syndrome is hypertriglyceridemia. We examined the gender differences between various metabolic factors related to insulin resistance in elderly non-diabetic men and postmenopausal women of comparable age suffering from hypertriglyceridemia, and compared them with healthy subjects of equal age. RESULTS: The indexes of insulin resistance HOMA IR and QUICKI were significantly higher in both hyperlipemic men and women than in controls; 95% confidence limits of hyperlipemic subjects did not overlap with controls. In both normolipemic and hyperlipemic men and women serum leptin correlated significantly with insulin resistance, while HDL-cholesterol correlated inversely with HOMA-IR only in women (both normo- and hyperlipemic), and serum tumor necrosis factor alpha (TNFalpha) only in hyperlipemic women. According to results of multiple regression analysis with HOMA-IR as a dependent variable, leptin played a significant role in determining insulin resistance in both genders, but--aside from leptin--triglycerides, TNFalpha and decreased HDL-cholesterol were significant determinants in women, while body mass index and decreased HDL-cholesterol were significant determinants in men. The coefficient of determination (R2) of HOMA IR by above mentioned metabolic variables was in women above 60%, in men only about 40%. CONCLUSION: The significant role of serum leptin in determination of insulin resistance in both elderly men and postmenopausal women of equal age was confirmed. However, the study also revealed significant gender differences : in women a strong influence of triglycerides, TNFalpha and decreased HDL-cholesterol, in men only a mild role of BMI and decreased HDL-cholesterol.