Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus.

BACKGROUND: Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters. METHODS: Eighty nT2DM and 80 age-, body mass index (BMI)-, and gender-matched NGT subjects were enrolled into this case-control study. The circulating UCN3 levels were measured using the enzyme-linked immunoabsorbent assay (ELISA). Metabolic parameters of enrolled subjects were also determined. A standard 75-g 2-hour oral glucose tolerance test was used for diagnosis of type 2 diabetes mellitus (T2DM). RESULTS: UCN3 levels were higher in subjects with nT2DM than in controls (115.64 ± 39.26 vs 86.16 ± 22.81 pg/mL, P < .001). UCN3 levels were increased in subjects with metabolic syndrome compared to subjects without metabolic syndrome in both nT2DM and NGT groups. UCN3 levels showed a positive correlation with BMI in both groups. Moreover, UCN3 levels were positively and independently associated with insulin, fasting blood glucose, insulin resistance, 2-hour plasma glucose, glycosylated hemoglobin, and triglycerides, whereas UCN3 levels were negatively and independently associated with high-density lipoprotein cholesterol. According to logistic regression analysis, increased risk of T2DM and metabolic syndrome were parallel with the highest elevated levels of UCN3. CONCLUSIONS: Increased levels of UCN3 are associated with unfavorable metabolic profiles in T2DM, indicating a potential role of UCN3 in glucose and lipid metabolisms in T2DM.

Fractalkine: an inflammatory chemokine elevated in subjects with polycystic ovary syndrome.

PURPOSE: Fractalkine (FKN) is an inflammatory chemokine related to reproductive system and glucose metabolism. There is a link between FKN and steroidogenesis as FKN induces progesterone synthesis. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with low progesterone production and insulin resistance. We aimed to explore whether women with PCOS have any difference in FKN levels compared to women without PCOS. We also focused on determination of any association between FKN levels and hormonal-metabolic parameters in women with PCOS. METHODS: The current research was designed as a case-control study. Eighty subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle were taken into the study. We measured circulating FKN levels via ELISA methods. RESULTS: Circulating FKN levels were higher in women with PCOS than controls (1.93 ± 0.61 vs. 1.22 ± 0.33 ng/ml, P< 0.001). FKN levels showed a positive correlation with body mass index (BMI), insulin resistance, inflammatory marker hs-CRP, total testosterone, and free-androgen index (FAI), whereas it showed a negative correlation with sex hormone-binding protein in women with PCOS. Linear regression analyses revealed that the link of FKN with BMI, insulin resistance, hs-CRP, and FAI was independent. Binary logistic regression analysis showed that the risk of having PCOS was associated with high levels of FKN. CONCLUSIONS: Increased FKN levels related to insulin resistance, inflammation and androgens in women with PCOS. FKN may have an inter-related role in different pathophysiologic pathways of PCOS.

Association of decreased C1q/tumor necrosis factor-related protein-5 levels with metabolic and hormonal disturbance in polycystic ovary syndrome

Objective: C1q/tumor necrosis factor-related protein-5 (CTRP5) is a novel peptide hormone involved in the metabolism of energy regulation. Polycystic ovary syndrome (PCOS), which is a reproductive and metabolic disorder, is associated with insulin resistance. The aim of the current study was to compare circulating levels of CTRP5 in women with and without PCOS and to investigate possible associations between CTRP5 and metabolic-hormonal parameters. Material and Methods: The present cross-sectional study contained 80 women with PCOS and 80 age and body mass index-matched women without PCOS. Circulating levels of CTRP5 were calculated using an enzyme-linked immunosorbent assay. We also measured hormonal and metabolic parameters. Results: Patients with PCOS had lower levels of circulating CTRP5 compared with women without PCOS (6.90±2.64 vs 11.73±3.66 ng/mL, p<0.001). CTRP5 was negatively correlated with insulin resistance, free-androgen index, and body mass index in both the PCOS and control groups. Moreover, patients with PCOS who had insulin resistance showed lower circulating CTRP5 levels compared with those without insulin resistance. In both the control and PCOS groups, overweight subjects had lower circulating levels of CTRP5 compared with participants of normal weight. Logistic regression analyses indicated that subjects in the lowest tertile for CTRP5 level had higher risk for PCOS compared with those in the highest tertile of CTRP5. Conclusion: Decreased circulating levels of CTRP5 were associated with higher risk of PCOS, as well as having metabolic disturbance among women with PCOS.

Association of kallistatin with carotid intima-media thickness in women with polycystic ovary syndrome.

BACKGROUND: Kallistatin is a secreted protein that acts as a tissue kallikrein inhibitor. It has anti-inflammatory, antioxidant and vasoprotective properties. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with low-grade chronic inflammation and multiple risk factors for cardiovascular diseases. The aims of this study were to ascertain whether circulating kallistatin levels are altered in women with PCOS, and whether there is an association between kallistatin and carotid intima-media thickness (cIMT) as well as inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). METHODS: This cross-sectional study included 75 women with PCOS and 75 age- and BMI-matched controls without PCOS. Circulating kallistatin and TNF-α levels were measured using ELISA. Metabolic and hormonal parameters, hs-CRP levels and cIMT were also determined. All subjects underwent the 2-hour oral glucose tolerance test (2-h OGTT). RESULTS: Circulating kallistatin levels were significantly elevated in women with PCOS compared to controls (6.31±2.09 vs. 4.79±2.26 ng/mL, P<0.001). Inflammatory markers hs-CRP and TNF-α were found to be elevated in women with PCOS. Kallistatin levels positively correlated with insulin, insulin resistance index (HOMA-IR), free androgen index, hs-CRP, TNF-α and cIMT in both PCOS and control groups. Kallistatin levels did not show correlation with BMI, blood pressure, fasting blood glucose, 2-h OGTT or HbA1c. Multiple linear regression analysis revealed that kallistatin is an independent predictor for cIMT (ß=0.131, 95% CI: 0.114-0.150, P=0.019). CONCLUSIONS: Kallistatin levels may provide useful information regarding cardiovascular risk in women with PCOS.