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.

[The Effects of Lithium on Calcium and Parathormone Levels: A Cross-sectional Study with Healthy Controls]. / Lityumun Kalsiyum ve Parathormon Düzeyi Üzerine Etkisi: Saglikli Kontrollerle Karsilastirmali Kesitsel Bir Çalisma.

OBJECTIVE: Despite lithium associated hyperparathyroidism (LAH) can lead to many complications, little notice has been paid to this sideeffect. The aim of this study was to investigate the effects of lithium on calcium and parathyroid hormone levels and the relation between lithium use and thyroid diseases. METHOD: This cross-sectional study was carried out with 87 lithiumtreated patients and 65 volunteers who had a similar age and gender distribution with the lithium group. Serum levels of corrected calcium, intact parathormone, phosphorus, magnesium, alkaline phosphatase, free thyroxine, thyroid stimulating hormone, thyroid autoantibodies and creatinine were assessed, and also, thyroid and parathyroid ultrasonography was conducted. Further detailed investigations were made depending on the elevation of the initially measured calcium and/ or parathormone levels. RESULTS: Median values of serum levels of the corrected calcium and the intact parathormone were significantly higher in the lithium group. Calcium levels had a mild correlation with the duration of lithium treatment. In the first assessment, while all control individuals had values within the normal reference range, 11 lithium-treated patients had corrected calcium and/or intact parathormone levels above the normal reference levels. All of the five patients, who were diagnosed with LAH after further investigation, were also diagnosed with a thyroid disorder. CONCLUSION: These results demonstrate that lithium treatment has a relationship with calcium and parathormone levels. The 5.7% prevalence of LAH and potential life-threatening conditions associated with LAH necessitates the use of available low-cost METHODS to monitor blood calcium levels of lithium-treated patients for early diagnosis.

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.

Thyroid Function and Ultrasonography Abnormalities in Lithium-Treated Bipolar Patients: A Cross-sectional Study with Healthy Controls.

INTRODUCTION: Lithium has many effects on thyroid physiology. Although these side effects have been known for a long time, large sample studies of lithium-treated patients using ultrasonography are lacking. The aim of this study is to investigate the detailed thyroid morphologies, hormone levels, and antibodies of lithium-treated patients compared with healthy controls. METHODS: This cross-sectional study involved 84 lithium-treated patients with bipolar disorder and 65 gender and age similar controls who had never been exposed to lithium. Subjects between 18 and 65 years of age were eligible for the study. Venous blood samples were acquired to determine the levels of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid antibodies; also, ultrasonographic examinations of the patients' thyroid glands were performed. RESULTS: There were no statistically significant differences in smoking habits, known thyroid disease, thyroid medication use, familial thyroid disease, fT4 level, autoimmunity, thyroid nodule presence, or Hashimoto's thyroiditis between the lithium and control groups. The median TSH level and thyroid volume were significantly higher in the lithium group. In the lithium group, 14 cases (16.7%) of hypothyroidism, seven cases (8.3%) of subclinical hypothyroidism, and one case (1.2%) of subclinical hyperthyroidism were defined; in the control group, seven cases (10.8%) of hypothyroidism and two cases (3.1%) of subclinical hyperthyroidism were defined. Thyroid dysfunction, goiter, parenchymal abnormality, ultrasonographically defined thyroid abnormality, and thyroid disorder were found to be more prevalent in the lithium group. 90% of patients with goiter and 74.3% of patients with ultrasonographic pathologies were euthyroid. CONCLUSION: It is important to note that 90% of the patients with goiter were euthyroid. This indicates that monitoring by blood test alone is insufficient. The prevalence rates of 47.6% for goiter and 83.3% for ultrasonographic pathology demonstrate that ultasonographic follow-up may be useful in lithium-treated patients. To determine whether routine ultrasonographic examination is necessary, large sample prospective studies are necessary due to the limitations of this study.

Endocan is a predictor of increased cardiovascular risk in women with polycystic ovary syndrome.

PURPOSE: Endocan is a proteoglycan secreted mainly from endothelial cells. It has been implicated that there is a link between endocan and endothelial dysfunction. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with increased risk of cardiovascular events. The aims of this study were to ascertain whether circulating endocan levels are altered in women with PCOS, and whether there is an association between endocan and carotid intima media thickness (cIMT). MATERIALS AND METHODS: This cross-sectional study included 80 women with PCOS and 80 age- and BMI-matched controls without PCOS. Circulating endocan levels were measured using ELISA. Metabolic, hormonal parameters and cIMT were determined. 2-h oral glucose tolerance test (2-h OGTT) was performed on all women. RESULTS: Circulating endocan levels were significantly elevated in women with PCOS compared with controls (5.99 ± 2.37 vs. 3.66 ± 1.79 ng/ml, P < 0.001). Endocan levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), high-sensitivity C-reactive protein (hs-CRP), and cIMT in both PCOS and control groups. Endocan levels did not correlate with fasting blood glucose, 2-h OGTT, A1C and lipid parameters. Multiple linear regression analysis revealed that endocan is an independent predictor for cIMT (ß = 0.128, 95% CI = 0.118-0.138, P = 0.011). CONCLUSIONS: Circulating endocan levels are significantly higher in women with PCOS and endocan is independently associated with cIMT. Elevated endocan levels can be a predictor of increased cardiovascular risk in PCOS subjects.

Increased adipsin is associated with carotid intima media thickness and metabolic disturbances in polycystic ovary syndrome.

CONTEXT: Adipsin, a protein secreted mainly from the adipose tissue, is a structural homologous of complement factor D, a rate-limiting enzyme of the alternative complement system. Growing evidence suggests that the alternative complement system plays a role both in the regulation of energy homoeostasis and in the atherosclerosis. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease. OBJECTIVE: To ascertain whether circulating adipsin levels are altered in women with PCOS, and whether there is an association between adipsin and metabolic parameters or carotid intima media thickness (CIMT). PARTICIPANTS: A total of 144 women with PCOS and 144 age- and BMI-matched controls without PCOS were recruited for this cross-sectional study. MAIN OUTCOME MEASURES: Circulating adipsin levels were measured using ELISA. Metabolic, hormonal parameters and CIMT were also determined. RESULTS: Adipsin levels were significantly elevated in women with PCOS compared with controls (91·52 ± 14·11 vs 60·31 ± 9·71 ng/ml, P < 0·001). Adipsin positively correlated with BMI, homoeostasis model assessment of insulin resistance (HOMA-IR), free testosterone, high-sensitivity C-reactive protein (hs-CRP) and CIMT in both groups. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 3·25 for patients in the highest quartile of adipsin compared with those in the lowest quartile (OR=3·25, 95% CI=2·64-4·00, P = 0·016). Our findings further indicate that BMI, HOMA-IR, hs-CRP and free testosterone are independent factors influencing serum adipsin levels and that adipsin is an independent predictor for CIMT. CONCLUSION: Circulating adipsin levels are significantly higher in women with PCOS, and the peptide is closely related to increased cardiovascular risk and metabolic disturbances.

Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome.

Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 ± 55.78 vs. 295.65 ± 48.97 pg/ml, P < 0.001). Betatrophin levels were positively correlated with insulin resistance marker homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone, high-sensitivity C-reactive protein (hs-CRP), atherogenic lipid profiles, and BMI in PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA-IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings.

Polycystic ovary syndrome is associated with increased osteopontin levels.

OBJECTIVE: Osteopontin (OPN) is a multi-functional secreted glycoprotein that plays a crucial role in glucose metabolism and inflammatory process. Growing evidence suggests that there is a link between OPN and ovarian function. However, no such link has yet been found for OPN in polycystic ovary syndrome (PCOS). Our aim was to ascertain whether circulating OPN levels are altered in women with PCOS and to determine whether OPN levels differ between the follicular phase and mid-cycle of the menstrual cycle in eumenorrheic women. DESIGN AND METHODS: In total, 150 women with PCOS and 150 age- and BMI-matched controls without PCOS were recruited for this prospective observational study. OPN levels were measured using ELISA. Metabolic parameters were also determined. RESULTS: Circulating OPN levels were significantly elevated in PCOS women compared with controls (69.12±31.59  ng/ml vs 42.66±21.28  ng/ml; P<0.001). OPN levels were significantly higher at mid-cycle than in the follicular phase in eumenorrheic women. OPN was positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free testosterone, and high sensitivity C-reactive protein (hs-CRP). Multivariate logistic regression analyses revealed that the odds ratio (OR) for PCOS was 3.64 for patients in the highest quartile of OPN compared with those in the lowest quartile (OR=3.64; 95% CI=2.42-5.57; P=0.011). Our findings indicate that BMI, HOMA-IR, hs-CRP, and free testosterone are independent factors influencing serum OPN levels and that OPN is an independent predictor for HOMA-IR. CONCLUSION: PCOS is associated with increased OPN levels.