Justyna Kuliczkowska-Płaksej

Subclinical impairment of left ventricular function in young obese women: contributions of polycystic ovary disease and insulin resistance.

CONTEXT Obesity and insulin resistance (IR) may produce disturbances of left ventricular (LV) function. Obese women with polycystic ovary syndrome (PCO), characterized by hormonal and metabolic abnormalities, are thought to be at particularly increased cardiovascular risk. OBJECTIVES We sought to determine the influence of IR on LV function in obese young women with and without PCO and without other comorbidities. DESIGN This was a cross-sectional study. SETTING The study was performed at a university hospital. PATIENTS A total of 150 women aged younger than 40 yr with a body mass index (BMI) of 30 kg/m(2) or more was classified into three groups: with both PCO and IR, without PCO and with IR, and without either PCO or IR. MAIN OUTCOME MEASURES Tissue Doppler-derived myocardial velocities, strain-rate and strain, and metabolic and hormonal measurements were calculated. RESULTS Subclinical impairment of LV systolic and diastolic function as indicated by lower peak strain (P < 0.001), peak systolic strain rate (P < 0.001), peak early diastolic strain rate (P < 0.001), and peak early diastolic velocity (P < 0.01) was demonstrated in both groups with IR. IR subjects with and without PCO did not differ in any LV function indices. Strain was independently associated with fasting insulin (beta = -0.39; P < 0.001), urinary albumin excretion (UAE) (beta = -0.36; P < 0.001), and BMI (beta = -0.22; P < 0.03), and peak early diastolic strain rate was associated with UAE (beta = -0.35; P < 0.001), fasting insulin (beta = -0.24; P < 0.02), BMI (beta = -0.23; P < 0.02), and SHBG (beta = 0.20; P < 0.04). CONCLUSIONS In obese young women, fasting insulin, BMI, SHBG, and UAE are independent correlates of impaired LV performance. The contribution of PCO to LV function abnormalities is linked to IR, but not to other hormonal aberrations associated with this condition.

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy

Aim. The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen–progestin therapies on concentration in pre- and postmenopausal women. Materials and methods. The study groups consisted of 26 women with surgical menopause (mean±standard deviation (SD): age 51.8±2.6 years, body mass index (BMI) 26.45±4.56 kg/m2), 54 with natural menopause (mean±SD: age 50.5±3.0 years, BMI 25.75±4.09 kg/m2) and 40 premenopausal controls (mean±SD: age 48.3±2.3 years, BMI 26.23±4.12 kg/m2). The group with surgical menopause received estradiol transdermally (50 μg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E2), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. Results. Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E2, FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. Conclusions. Endogenous E2 and androgens in premenopausal women and estrogen and estrogen–progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.

Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution

Abstract Irisin (Ir), a recently identified adipo-myokine, cleaved and secreted from the protein FNDC5 in response to physical activity, has been postulated to induce the differentiation of a subset of white adipocytes into brown fat and to mediate the beneficial effects on metabolic homeostasis. Metabolic syndrome (MS), a cluster of factors leading to impaired energy homeostasis, affects a significant proportion of subjects suffering from polycystic ovary syndrome (PCOS). The aim of our study was to investigate the relationship between Ir plasma concentrations and metabolic disturbances. The study group consisted of 179 PCOS patients and a population of 122 healthy controls (both groups aged 25–35 years). A subset of 90 subjects with MS was isolated. A positive association between Ir plasma level and MS in the whole group and in controls was found. In subjects with high adipose body content (>40%), Ir was higher than in lean persons (<30%). Our results showed a significant positive association between Ir concentration and android type of adipose tissue in the whole study group and in the control group. Understanding the role of Ir in increased energy expenditure may lead to the development of new therapeutics for obesity and obesity-related diseases. Chinese abstract 鸢尾素（Ir）,一个新近被发现的脂肪-肌肉细胞因子，由蛋白FNDC5在体力活动时产生应答而裂解和分泌，推测其诱导白色脂肪细胞亚单位分化为棕色脂肪，并介导棕色脂肪对代谢稳态的有益作用。代谢综合征（MS），一系列因素导致能量稳态受损，影响了相当比例的多囊卵巢综合征（PCOS）患者。我们的研究旨在探讨Ir的血浆浓度与代谢紊乱间的关系。实验组包含179名PCOS患者和122名健康对照人群（两组年龄均为25-35岁）。其中90名患有MS的受试者。实验组和对照组均发现Ir血浆浓度和MS呈正相关。在体脂含量较高（＞40%）的受试者中，Ir水平在比较瘦的患者（＜30%）高。我们的结果显示实验组和对照组的Ir浓度和雄性脂肪组织呈显著正相关。了解Ir在增加能量消耗中的作用可能有助于发展肥胖和肥胖相关疾病的新的治疗方法。

Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), rs10735810 (FokI): a case–control study of lower Silesian women

Abstract Context: The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial. Objective: The objective of this study was to investigate for the first time in women with “classic” PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology. Design: Ninety-two women with “classic” PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed. Results: Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with “classic” PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups. Conclusions: For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous “classic” PCOS phenotype.

Accumulation of abdominal fat in relation to selected proinflammatory cytokines concentrations in non-obese Wrocław inhabitants.

INTRODUCTION Metabolically obese normal weight (MONW) subjects, despite their normal BMI, present metabolic disturbances characteristic of abdominal obesity. One of the reasons might be subclinical inflammation caused by the fat tissue excess. The aim of this study was to assess the association between the accumulation of fat (especially abdominal) and the concentration of selected proinflammatory cytokines - interleukins (IL-6, IL-18) and C-reactive protein (CRP). MATERIAL AND METHODS The study population consisted of 342 subjects (218 women, 124 men; age 20-40 years, BMI < 27 kg/m2) recruited from a community centre in Wroclaw. The group was divided based on the homeostasis assessment insulin resistance index (HOMA) value: 90 MONW subjects with HOMA > 1.69 and 252 subjects as control group. Anthropometric parameters, serum IL-6, IL-18, CRP, glucose, insulin concentrations and insulin sensitivity/resistance indexes were evaluated. RESULTS CRP levels were significantly higher (3.26 vs. 1.97, p = 0.03) in MONW women than in the control group. Serum IL-6, IL-18 levels in males and females did not differ in both groups. IL-6 showed a significant correlation with the abdominal to gynoidal fat tissue deposit ratio in women. There were correlations between the CRP and BMI, WHR, waist circumference, total fat, abdominal fat deposit, and abdominal to gynoidal fat deposit ratio in both sexes. In women, positive correlations between CRP and HOMA, FIRI and negative with QUICKI index were present. CONCLUSIONS Increased accumulation of abdominal adipose tissue in non-obese, young and healthy subjects is related to increased CRP levels.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome — clinical and metabolic aspects and lipoprotein lipase gene polymorphism

INTRODUCTION The aim was to assess associations among PCOS and NAFLD, the lipoprotein lipase polymorphism gene, and metabolic disorders in PCOS. MATERIAL AND METHODS In 184 women with PCOS and 125 healthy, premenopausal volunteers, sex steroids, lipids, glucose, insulin, aminotransferases, free androgen index (FAI), HOMA-IR and E2/T were calculated. Hepatic steatosis was determined by ultrasound. Whole genomic DNA was isolated from blood leucocytes. Lipoprotein lipase polymorphisms rs268 and rs328 were analysed by polymerase chain reaction (PCR) and minisequencing. RESULTS 57.6% of PCOS women had NAFLD, while women without PCOS had NAFLD in 49.6%. PCOS-NAFLD women had higher BMI, WHR and waist circumference compared to women with PCOS without NAFLD and women without PCOS. PCOS-NAFLD women had lower SHBG, E2/T ratio, and higher FAI compared to other groups. ALT levels were higher in PCOS women with NAFLD compared to other groups. PCOS women with and without NAFLD had higher fasting glucose and insulin and HOMA compared to women without PCOS. Women with PCOS had higher triglycerides and lower HDL-C compared to women without PCOS. There was no evidence that evaluated polymorphisms influenced hepatic steatosis in women with and without PCOS. CONCLUSIONS PCOS is not an independent factor influencing NAFLD in women. The influences on NAFLD incidence in women are BMI > 25 kg/m², glucose level > 80 mg/dL, E2/T < 80 and ALT > 19 IU/L as independent factors. Hyperandrogenism in PCOS may increase the risk of NAFLD indirectly by obesity, insulin resistance, and directly by the hepatotoxic effect. Polymorphisms rs328 and rs268 of the lipoprotein lipase gene do not affect the occurrence of NAFLD in women with PCOS or without PCOS.

Neuroendocrine control of metabolism

Metabolism is controlled through homeostatic system consisting of central centers, gut hormones, hormones from adipose tissue and the other hormonal axes. This cooperation is based on cross-talk between central and peripheral signals. Among them the hypothalamus plays a crucial role, with interconnected nuclei forming neuronal circuits. Other regions in the brain, such as the brain stem, the endocannabinoid system, the vagal afferents, are also involved in energy balance. The second component is peripheral source of signals − the gastrointestinal tract hormones. Additionally, adipokines from adipose tissue, thyrotropic, gonadotropic and somatotropic axes play a role in energy homeostasis. Knowledge about all components of this neuroendocrine circuit will be helpful in developing novel therapeutic approaches against the metabolic syndrome and its components.

Androgen receptor polymorphism and platelet reactivity in healthy men

There is established evidence of gender differences in the prevalence and severity of vascular thrombosis and mortality, with men having onset of coronary artery disease earlier in the life thanwomen, andwith first symptoms more often being myocardial infarction [1]. The impact of sex hormones on gender differences in platelet activity (one of the main factors in atherothrombosis) is also being increasingly recognized [2]. One of the “culprit” hormoneswhich could play a role in that setting is testosterone, which seems to have an influence on platelet activity, although the available data are conflicting. Some experimental studies show that in castrated rats given testosterone to physiological levels, enhanced platelet aggregation present after castration [3,4] and atherosclerotic plaque growth are inhibited [5]. Testosterone deprivation can also be harmful in men with prostate cancer treated with anti-androgenic therapy [6]. By contrast, in another study, exogenously administered testosterone up-regulated the population of thromboxane A2 (TXA2) receptors onplatelets in healthy youngmale volunteers, and this was concomitant with an enhanced aggregation response to TXA2mimetic I-BOP [7]. In yet another study, the reduction in circulating testosterone concentration following castration was associated with a significant reduction in platelet TXA2 receptor density and maximum aggregation response to TXA2-mimetic I-BOP[8]. Available data therefore suggest that testosterone influences platelet aggregation through increasing or decreasing TXA2 receptor density on the platelet surface. The mechanism for this action is largely obscure. A recent study has suggested the presence of androgen receptors (ARs) within platelets. In this study ADP-induced platelet aggregation was associated with platelet cytosolic binding to radiolabeled testosterone [9]. What is more, humanmegakaryocytes generated ex vivo expressed RNA for AR, confirmed by Western immunoblotting to be present in humanplatelets in another study [10]. These in vitro effects of testosteroneonplatelet aggregation suggestnon-genomic actionsonplatelets, or the presence of functional AR within platelets, which modulate the response to TXA2-induced platelet aggregation [10]. One possible pathway could involve testosterone linking to ARs in platelet cytosol, which in turn up-load TXA2 receptors onto the platelet surface, enhancing aggregation induced by I-BOP (TXA2-receptor agonist). The strength of the testosterone action in vivo is dependent on testosterone level and AR density and structure. ARs are expressed in vascular endothelium, in smooth muscle cells, and presumably within platelets.Genetically, theyareencodedonchromosomeX(locusq11–12). The polyglutaminic sequence coding region is the mostly polymorphic one in that gene and accounts for the transcript activity of the final product. It consists of a periodically repeating nucleotide triplet, the socalled CAG (cytosine, adenine, guanine) repeats [11]. Genetic variations of the AR gene – principally fewer CAG repeats in the amino-terminal domain – has been associated with higher testosterone levels in women

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome – a pilot study

Abstract Objective: Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD). Design: The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS. Methods: Sixty-two women with PCOS according to the Rotterdam criteria (20–35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated. Results: The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group. Conclusion: The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

Thyroid Disorders in Climacteric Women

The appearance of menopause is combined with the incidence of many diseases typical of middle age, i.e., thyroid disorders, osteoporosis, and cardiovascular diseases. Thyroid disorders, especially subclinical hypothyroidism and subclinical hyperthyroidism, are frequent medical conditions among postmenopausal women. The prevalence of metabolic syndrome and osteoporosis significantly increases in postmenopausal women [1]. Many symptoms appear due to decreased estrogen level; however, chronic diseases influence quality of life as well. One of them is thyroid diseases, which are associated with risk factors for osteoporosis and cardiovascular diseases. Some symptoms of chronic diseases may mimic or modify the clinical expression of climacteric symptoms. Menopause and thyroid disease may present with similar symptoms, i.e., sweating, heart palpitations, insomnia, irritability, or mood changes, which suggest menopause, hyperthyroidism, or both. In addition, weight gain, constipation, skin atrophy, and hair atrophy are climacteric symptoms as well as symptoms of hypothyroidism [2]. With aging, the level of thyroid-stimulating hormone (TSH) remains within normal range and occasionally has a tendency to increase [3]. Reduction of thyroid iodine uptake, free thyroid hormone synthesis, and catabolism of free thyroxine (FT4) are observed. In addition, reverse triiodothyronine (rT3) level increases [3].