Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome.

We aimed to determine plasma levels of growth and differentiation factor (GDF)-9 and GDF-15, and their possible association with bone turnover parameters and bone mineral density (BMD), in patients with polycystic ovary syndrome (PCOS). Forty-two obese PCOS women aged 25-35 years, 23 women with idiopathic hirsutism (IH) and 20 healthy controls matched for age and body mass index were enrolled. Anthropometric, metabolic and hormonal patterns, plasma GDF-9 and GDF-15 concentrations, bone turnover markers and BMD were measured. No significant differences were observed in bone turnover markers, BMD measurements, plasma GDF-9 and GDF-15 levels in subjects with PCOS compared with the other two groups. In the combined population of all three groups, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.317, p < 0.01). Analysis of PCOS patients showed a significant correlation of GDF-15 concentrations with age and homeostasis model assessment index (r = 0.319, p < 0.05, and r = 0.312, p < 0.05, respectively). In addition, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.395, p < 0.01) and positively correlated with urine deoxypyridinoline (r = 0.353, p < 0.05). GDF-9 did not correlate with bone markers and BMD measurements. In conclusion, plasma GDF-9 and GDF-15 levels as well as bone turnover markers and BMD measurements in subjects with PCOS (25-35 years of age) were comparable with those either in subjects with IH or in healthy controls with similar anthropometric and metabolic profiles. GDF-15 might be a marker of a crossregulation between bone and energy metabolism.

Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome.

BACKGROUND: Nesfatin-1 is a recently discovered neuropeptide derived from its precursor nucleobindin-2 (NUCB2) and has been implicated in the regulation of feeding and energy metabolism. It is located in the brain and also produced at the periphery and present in the plasma. However, its pathophysiological role in humans remains unknown. Polycystic ovary syndrome (PCOS) is commonly presented with obesity, insulin resistance, hyperandrogenemia and hirsutism. AIM: To characterize serum nesfatin-1 levels in PCOS women and determine association of nesfatin-1 with metabolic parameters. MATERIALS AND METHODS: It is a cross-sectional study of 55 PCOS and 28 healthy women matched in age, in a university hospital setting. Anthropometric, hormonal, metabolic parameters and nesfatin-1 blood levels were determined. RESULTS: Nesfatin-1 levels were significantly higher in PCOS group compared with the controls 371.43 ± 2.50 versus 275.55 ± 1.74 pg/mL. Multivariate logistic regression analysis that contains: nesfatin-1, body mass index and homeostasis model assessment index revealed significant correlation of nesfatin-1 with the existence of PCOS (p < 0.05). CONCLUSIONS: Higher nesfatin-1 levels in PCOS women compared to control group may suggest a possibility that nesfatin-1 may play some role in the PCOS.

Higher levels of circulating CXCL-9 and CXCL-11 in euthyroid women with autoimmune thyroiditis and recurrent spontaneous abortions.

BACKGROUND: We aimed to measure serum CXCL-9 and CXCL-11 levels in patients with autoimmune thyroiditis (AIT) and recurrent spontaneous abortions (RSA). METHODS: Forty-one euthyroid, non-pregnant women with AIT and a history of unexplained first trimester RSA, 35 euthyroid women with AIT, and 29 healthy controls matched for age and body mass index were enrolled. Serum CXCL-9 and CXCL-11 were measured. RESULTS: Serum CXCL-9 and -11 levels were significantly higher (p < 0.001 for both) in the antibody-positive women with a history of abortions than in both control groups. Additionally, CXCL-9 levels were higher in patients with AIT without RSA than in healthy controls. No significant differences were found in CXCL-9 and -11 levels in subjects with a history of RSA in relation to the number of previous abortions. In multiple linear regression analyses, abortions were significantly related to CXCL-9 (ß-coefficient = 0.174, p < 0.001), CXCL-11 (ß-coefficient = 0.490, p < 0.001). CONCLUSION: Higher circulating levels of CXCL-9 and -11 have been shown in non-pregnant AIT patients with a history of RSA as compared to both control groups, suggesting that this subgroup produce a more dominant Th-1 cytokine profile.

Increased total Renin levels but not Angiotensin-converting enzyme activity in obese patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the renin-angiotensin-aldosterone system and angiotensin-converting enzyme (ACE) activity in patients with polycystic ovarian syndrome (PCOS). SUBJECTS AND METHODS: In this case-control study, 41 obese (PCOS) women and 29 healthy controls, matched for age and body mass index, were enrolled. Anthropometric, metabolic, and hormonal patterns, including plasma aldosterone, plasma renin, and ACE activity, were measured in each subject. RESULTS: Plasma renin levels were significantly higher in PCOS patients (19.7 ± 14.5 µg/ml) compared with controls (12.9 ± 9.0 µg/ml, p < 0.05). ACE activity and aldosterone levels did not significantly differ between both groups (p = 0.15 and p = 0.18, respectively). Analysis of PCOS patients showed a significant correlation of fasting insulin levels with levels of renin (r = 0.305, p < 0.01) and free testosterone (r = 0.384, p = 0.001). Similarly, homeostasis model assessment index was positively correlated with total renin concentrations (r = 0.366, p < 0.01) and free testosterone (r = 0.352, p < 0.01). CONCLUSION: Obese PCOS women had higher total renin levels, but not ACE activity and aldosterone levels, related to insulin resistance compared with controls.

Rosiglitazone decreases fasting plasma peptide YY3-36 in type 2 diabetic women: a possible role in weight gain?

Rosiglitazone often results in weight gain. We hypothesized that rosiglitazone may modulate circulating levels of ghrelin and peptide YY(3-36) and this modulation may be related to weight-gaining effect of this agent. This study was designed as an open-label, randomized, controlled trial of 3-month duration. Women with newly diagnosed type 2 diabetes were studied. Twenty-eight of the 55 eligible participants were randomly assigned to receive rosiglitazone (4 mg/d). Twenty-seven patients with diabetes matched for age and body mass index served as controls on diet alone. We evaluated the effects of 3 months of rosiglitazone treatment on fasting peptide YY(3-36) and ghrelin levels, and anthropometric measurements. The 3-month administration of rosiglitazone reduced fasting plasma peptide YY(3-36) levels by 25%, the between-group difference was statistically significant. No effect of this thiazolidinedione compound on fasting ghrelin concentrations was observed at the end of study. The ghrelin/body mass index ratio also did not change significantly after treatment. Seventy-five percent of the women with diabetes complained of increased hunger at the end of study. Nevertheless, all subjects exhibited a decrease in fasting PYY levels after 3 months of rosiglitazone therapy, irrespective of the levels of hunger. There was no significant correlation between changes in peptide YY(3-36) and those in anthropometric parameters and insulin sensitivity at the end of the study. Rosiglitazone-induced decrease in fasting peptide YY(3-36) levels may in part contribute to orexigenic and weight-gaining effect of this thiazolidinedione derivative.

Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study.

OBJECTIVE: To evaluate the effect of rosiglitazone on bone metabolism and bone density. DESIGN: An open-label, randomized, controlled trial of 24-month duration. Patients and measurements Obese, postmenopausal women with newly diagnosed diabetes were studied. Before and after the intervention, metabolic bone markers and bone density were assessed. RESULTS: Twenty-six patients received rosiglitazone (4 mg/day), and 23 remained on diet alone. Serum bone-specific alkaline phosphatase and osteocalcin levels decreased by 17% (P < 0.001 vs control group) and 26% (P < 0.01 vs control group), respectively, in the rosiglitazone group. There were no significant changes in the deoxypyridinoline levels between the two groups. Annual bone loss at the trochanter and at the lumbar spine associated with each year of rosiglitazone use was 2.56% (P = 0.01 vs control group) and 2.18% (P < 0.01 vs control group), respectively. Femoral neck and total hip bone density declined significantly in both groups (P < 0.01, and P = 0.01, respectively) but was not significantly different between the two groups. CONCLUSIONS: Rosiglitazone treatment adversely affects bone formation over a 2-year period. It increases bone loss at the lumbar spine and trochanter in postmenopausal, type 2 diabetic women. However, bone loss at the total hip did not differ with use of this agent.

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism.

BACKGROUND: Brain natriuretic peptide (BNP) is secreted from the ventricular myocardium in response to volume expansion and pressure overload. Serum BNP levels are also affected by thyroid function status, which was mostly related to a direct stimulatory effect of thyroid hormones on the secretion of BNP. Although the diagnostic value of BNP in heart failure is undisputed, its value in the presence of the thyroid dysfunction has been recently questioned. The aim of this study was to evaluate the influence of thyroid dysfunction on BNP levels. METHODS: Evaluation of 18 overt and 47 subclinical hyperthyroid patients together with 39 subclinical and 13 overt hypothyroid patients was carried out in a cross-sectional study. Thirty-three age-, sex- and body mass index (BMI)-matched control subjects were also included. RESULTS: BNP levels were more than five times higher in hyperthyroid than euthyroid control subjects (P < 0.001). BNP levels were also higher in subclinical hyperthyroidism than euthyroid control subjects (P = 0.09). Correlation analysis revealed that free T4 and free T3 concentrations were associated with high serum BNP levels. The BNP level in patients with subclinical or overt hypothyroidism was similar to that of the controls. CONCLUSION: The current study provides additional insight into the diagnostic value of BNP in the presence of coexistent thyroid dysfunction and demonstrates important independent effects of thyroid hormones upon BNP plasma concentrations.

Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women.

OBJECTIVES: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. DESIGN: This was a 12-wk open-label randomized-controlled trial. PATIENTS OR OTHER PARTICIPANTS: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study. INTERVENTIONS: The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone. MAIN OUTCOME MEASURES: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. RESULTS: Serum total alkaline phosphatase (ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1beta and TNF-alpha levels compared with baseline. Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group. CONCLUSIONS: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.

Effects of raloxifene on platelet functions in patients with postmenopausal osteoporosis.

Many studies have addressed the effects of estrogenic compounds on platelet function. Raloxifene is a selective estrogen receptor modulator (SERM), which is currently used for the treatment of postmenopausal osteoporosis. At present, there are no clinical data about the effects of raloxifene on platelet function. The purpose of this study was to determine if raloxifene at therapeutic doses affects platelet function in patients with postmenopausal osteoporosis. The effects of raloxifene on platelet function were investigated using a commercial platelet function analyzer (PFA-100) with collagen epinephrine and collagen adenosine 5'-diphosphate (ADP) cartridges. We studied platelet function of 30 patients with postmenopausal osteoporosis before and 15 days after initiation of raloxifene 60 mg/daily. Closure times did not differ significantly between samples obtained before (117.8 +/- 20.5 s) and after raloxifene therapy (106.5 +/- 25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no statistically significant difference in mean closure times with collagen/ADP cartridges at baseline (86.2 +/- 18.5 s) and after raloxifene therapy (84.4 +/- 13.8 s) (P > 0.05). Platelet counts (278.3 +/- 72.9 vs. 262.4 +/- 56.7 109/L, P > 0.05) and mean platelet volumes (8.9 +/- 1 vs. 9.1 +/- 1 fL, P > 0.05) were not different before and after raloxifene therapy. Although estrogen related compounds do affect platelet function, there is suggestive data in our study that raloxifene in therapeutic dose exhibit no effect on platelet function in patients with postmenopausal osteoporosis.