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OBJECTIVE -To evaluate insulin sensitivity (IS) and ␤-cell function (␤F) in lean and obese women with polycystic ovary syndrome (PCOS), either separately or by using a disposition index (DI).RESEARCH DESIGN AND METHODS -A total of 64 women with PCOS and 20 healthy women were examined by anthropometry, oral glucose tolerance tests (OGTTs), and insulin tolerance tests. Statistical analysis used one-way ANOVA, Kruskal-Wallis, and MannWhitney U tests, as appropriate.RESULTS -A significantly higher waist-to-hip ratio (P Ͻ 0.0001) was found in both lean and obese women with PCOS. Higher basal blood glucose (P Ͻ 0.004) and blood glucose values at 3 h of OGTT (P Ͻ 0.008) were found in lean and obese PCOS subjects in comparison with control subjects. Insulin resistance by homeostasis model assessment (P Ͻ 0.007) was significantly higher in obese PCOS than in control or lean PCOS subjects. Early-phase insulin secretion (insulinogenic index [⌬I/⌬G 30 -0 , where I is insulin and G is glucose]; P Ͻ 0.0007) was significantly higher in both lean and obese PCOS subjects than in healthy women. All tested combinations of parameters of IS and ␤F (DIs) followed a physiological hyperbolic relationship.Significantly lower values of the fasting state-derived DIs were found (all P Ͻ 0.05) in obese PCOS subjects. Significantly higher values of all of these indexes derived from nonfasting values were found in lean PCOS as compared with control and obese PCOS subjects (all P Ͻ 10 -3 ).

In the whole cohort of 528 subjects, the G allele was observed with a frequency of 0.26. Genotypic distribution did not differ between diabetics and controls. However, in the offspring of DM2 patients, significantly higher BMI and a trend towards higher waist to hip ratio, waist to height ratio, waist circumference, and subcutaneous fat mass was observed in the AG genotype compared with the wild-type. Similar tendency was evident in the control group. This indicates possible involvement of the A-3826G polymorphism in the regulation of body composition.

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is known to influence several phenotypes, including polycystic ovary syndrome (PCOS), diabetes mellitus type 1, diabetes mellitus type 2, and birth weight. The presence of the class III allele of INS VNTR has been reported to be protective in diabetes mellitus type 1, but in contrary it increases the disease risk of PCOS and diabetes mellitus type 2. PCOS is a very common endocrinopathy in women of reproductive age. The etiology of PCOS is uncertain, but family history of this syndrome suggests a major genetic cause. The aim of this pilot study was to investigate the possible association of INS VNTR polymorphism with PCOS in Czech women. In PCOS, significantly higher WHR, BMI, G0, G180, I30, Cp0, Cp30, Cp60, AUC‐I, AUC‐Cp, and insulinogenic index and significantly lower AUC‐G/AUC‐I were found. No significant differences in INS VNTR genotype, phenotype, or allele frequencies were found between PCOS and controls. In spite of several differences in anthropometric and biochemical parameters (abdominal fat localization, increased β‐cell function, and lower insulin sensitivity in PCOS women), no effect of INS VNTR polymorphism was found on insulin secretion, insulin action, or any other screened parameter.

Metabolic syndrome is a prevalent, complex condition. The search for genetic determinants of the syndrome is currently undergoing a paradigm enhancement by adding systems genetics approaches to association studies. We summarize the current evidence on relations between an emergent new candidate, zinc finger and BTB domain containing 16 (ZBTB16) transcription factor and the major components constituting the metabolic syndrome. Information stemming from studies on experimental models with altered Zbtb16 expression clearly shows its effect on adipogenesis, cardiac hypertrophy and fibrosis, lipid levels and insulin sensitivity. Based on current evidence, we provide a network view of relations between ZBTB16 and hallmarks of metabolic syndrome in order to elucidate the potential functional links involving the ZBTB16 node. Many of the identified genes interconnecting ZBTB16 with all or most metabolic syndrome components are linked to immune function, inflammation or oxidative stress. In summary, ZBTB16 represents a promising pleiotropic candidate node for metabolic syndrome.