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1.
Abstract

To assess the effect of glucophage, magnesium oxide and spironolactone in altering free fatty acids (FFAs), 36 PCOS women were randomly divided into three groups. Group 1 (n?=?14) was treated with 500?mg glucophage po bid, group 2 (n?=?10) was treated with 400?mg magnesium oxide po bid and group 3 (n?=?12) was treated with 50?mg spironolactone po bid for 12 weeks. A glucose tolerance test with 75?g glucose load was performed before and after treatment, collecting blood at 0, 1 and 2?h for insulin, glucose, FFA and aldosterone. Amount of FFA before and after treatment were compared by repeated measure ANOVA and represented as area under the curve. FFA levels before treatment were 0.83?±?0.23, 0.77?±?0.15 and 0.85?±?0.28 and after treatment were 0.77?±?0.48, 0.71?±?0.18 and 0.66?±?0.25 for glucophage, magnesium oxide and spironolactone-treated patients, respectively. The FFA levels were unchanged in the groups treated with glucophage and magnesium oxide but were significantly (p?<?0.03) decreased in the group treated with spironolactone. Since FFAs are known to be involved in the development of insulin resistance, these results suggest that spironolactone may be useful for lowering insulin resistance in PCOS patients.  相似文献   

2.
目的探讨小檗碱(BBR)作为胰岛素增敏剂对多囊卵巢综合征(PCOS)的治疗效果。方法 2009年10月至2010年10月在哈尔滨医科大学附属第一医院将因不孕症就诊的PCOS合并胰岛素抵抗(IR)的患者随机分为4组,A组:复方环丙孕酮(CPA)+BBR;B组:CPA+二甲双胍(MET);C组:CPA+BBR+MET;D组:单用CPA。治疗前及治疗3个月后检测临床表现、性激素、糖脂代谢指标并加以比较。结果 A、B、C、D4组治疗后患者体重、BMI、WHR均降低,体重与BMI的改善4组间无统计学意义;WHR的改善A、C组更为显著(P<0.01)。A、B、C3组治疗后FIN、FPG以及HomaIR、AUCINS均明显下降,治疗前后比较差异有统计学意义(P<0.01);FIN、HomaIR、AUCINS降低程度表现为:C组优于A及B组(P<0.01);D组仅表现为AUCINS在治疗后有所下降。A、B、C3组治疗后TG、TC、LDL-C均有下降,HDL-C有所升高(P<0.05),A、C组优于B组(P<0.01),但C组与A组比较TG降低及HDL-C升高更显著(P<0.01),D组患者血脂变化在治疗前后无显著差异。与治疗...  相似文献   

3.
目的探讨多囊卵巢综合征(PCOS)患者血清一氧化氮(NO)水平与其血管并发症的关系。方法采用硝酸还原酶法测定27例PCOS患者(PCOS组),21例因男方因素或输卵管因素不孕患者(对照组)血清NO水平,测定并计算体重指数(BMI)、腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、体脂含量、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(IAI)、血清性激素、空腹血糖(FPG)和胰岛素(FINS)水平。结果非肥胖PCOS组的HOMA-IR高于非肥胖对照组,IAI、血清NO水平低于非肥胖对照组,差异均有显著性(P〈0.05)。非肥胖PCOS组IAI明显高于肥胖PCOS组,差异有显著性(P〈0.01)。血清NO水平在PCOS组和其对照组间差异无显著性(P〉0.05)。PCOS组中,血清NO水平与HOMA-IR(r=-0.317,P〈0.05)、体脂含量(r=-0.346,P〈0.05)呈负相关。结论PCOS患者血清NO水平降低,提示PCOS患者可能存在血管内皮功能受损。  相似文献   

4.
As a new hormone, betatrophin has gained attention as a potential new target to combat insulin resistance (IR) and diabetes. Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of the reproductive age with long term sequelae which include IR and metabolic syndrome. The aim of this study is to evaluate the circulating plasma betatrophin levels in overweight/obese or lean women with or without PCOS and also to elucidate possible correlations with anthropometric and metabolic parameters. Thirty-two patients with PCOS as well as fifty-three control subjects were enrolled after obtaining informed written consent. Clinical and biochemical parameters of all subjects were determined. Plasma adiponectin, GLP-1 and betatrophin levels were measured by ELISA. Plasma betatrophin levels were significantly increased in lean patients with PCOS compared with lean and obese controls. Moreover, in PCOS group, betatrophin levels were significantly negatively correlated with waist hip ratio (WHR), fasting insulin level (FINS) and HOMA-IR, whereas, significantly positively correlated with adiponectin level. Multiple regression analysis showed that HOMA-IR was an independent factor influencing serum betatrophin levels. Further follow-up studies are needed to highlight whether and how increased betatrophin secretion play an important role in IR and carbohydrates metabolism in patients with PCOS.  相似文献   

5.
Abstract

Aims: To demonstrate the effects of DHEAS/free testosterone (DHEAS/FT) ratio on metabolic parameters in women with and without polycystic ovary syndrome (PCOS).

Methods: The data of 91 women with PCOS and 66 women in the control group were collected retrospectively.

Results: DHEAS/FT of the control group was higher than that of PCOS group (684.93?±?300.54 to 517.2?±?300.8, p?<?0.001). DHEAS/FT correlated with BMI (r?=??0.352, p?=?0.001), WHR (r?=??0.371, p?=?0.0219), LDL (r?=??0.227, p?=?0.031), HOMA-IR (r?=??0.36, p?=?0.001) and FAI (r?=??0.639, p?=?0.001) negatively and with HDL (r?=?0.344, p?=?0.001) and SHBG (r?=?0.646, p?=?0.001) positively. In the control group, DHEAS/FT correlated with BMI (r?=??0.334, p?=?0.007), CRP (r?=??0.297, p?=?0.016) and FAI (r?=??0.399, p?=?0.01) negatively.

Conclusions: High DHEAS/FT ratios are related to a better metabolic phenotype in women with PCOS and low levels can be used to detect women with PCOS that have a higher risk of metabolic problems.  相似文献   

6.
Aim: To evaluate the relationship between measures of body adiposity and visceral adiposity index (VAI) and risk of metabolic syndrome (MS) and to identify the optimal cut-off points of each measurement in Thai polycystic ovary syndrome (PCOS).

Methods: A cross-sectional study was completed physical examination, fasting plasma glucose, lipid profiles of 399 PCOS and 42 age-matched normal controls. Body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and VAI were calculated. Associations between different measures and MS were evaluated and the receiver-operating characteristic (ROC) curve was performed to determine appropriate cut-off points for identifying MS.

Results: Percentage of MS in PCOS was 24.6%, whereas none MS in controls. Previously recommended cut-off values for body adiposity and VAI were significantly associated with MS. ROC curve analysis of the only PCOS showed newly obtained optimal cut-off points for BMI and VAI of ≥28?kg/m2 (AUC?=?0.90) and >5.6 (AUC?=?0.94), respectively. Values found to be more accurate than the original ones. VAI was the best predictor, followed by BMI and WHtR.

Conclusion: All body adiposity and VAI parameters can predict the risk of MS. Optimal values for Thai PCOS were ≥28?kg/m2 for BMI, ≥0.85 for WHR, ≥0.5 for WHtR and >5.6 for VAI.  相似文献   

7.
Objective: To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters

Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters.

Results: Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels.

Conclusion: WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.  相似文献   


8.
Objective. To investigate glyco-lipidic metabolism and androgenic profile in a cohort of women with polycystic ovary syndrome (PCOS) divided according to Rotterdam phenotypes and body mass index (BMI).

Design. A prospective case–control study.

Setting. Gynecology department in a teaching hospital.

Patients. A total of 223 PCOS women and 25 healthy control women were studied.

Methods. Patients and controls were subdivided into three groups according to their BMI: normal weight (18.5?≤?[BMI]?≤24.9?kg/m2), overweight (25.0?≤?BMI?≤29.9?kg/m2), or obese (BMI?≥30.0?kg/m2) and according to Rotterdam criteria of PCOS.

Main outcome measures. Pituitary-gonadal axis assessment including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, PRL, testosterone, androstenedione, DHEA-S, 17-hydroxyprogesterone and inhibin B. Metabolic parameters included cholesterol (Chol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and apolipoproteins (APO) AII and B as well as serum fasting insulin, glucose and HOMA-IR.

Results. Serum fasting insulin, glucose, HOMA-IR, TG and HDL were significantly higher in women with PCOS compared to controls. Additionally, serum levels of Chol, LDL and TG were significantly higher and HDL levels were significantly lower in obese PCOS women compared with overweight/normal PCOS irrespective of Rotterdam phenotypes. Free testosterone index but not androstenedione or total testosterone significantly correlated with TG, HDL and APO B. No significant correlations were detected between gonadotropins, inhibin B or estradiol with metabolic parameters studied.

Conclusions. Obesity but not overweight in PCOS is associated with dyslipidemia. Hyperandrogenic women showed the most atherogenic lipid profiles.  相似文献   

9.
Introduction: This paper provides a critical review of the data concerning the effects of combined hormonal contraceptives (CHC) for polycystic ovary syndrome (PCOS). The aim is to determine the best treatment option for each PCOS phenotype.

Study design: A literature search of the PubMed database was conducted for randomized clinical trials (RCTs) and observational studies published in any language prior to October 2013. Hyperandrogenism (HA) is the essential diagnostic criterion for PCOS and is frequently associated with insulin resistance (IR) or obesity. The combinations of these criteria define the different PCOS phenotypes and establish the scale of metabolic and cardiovascular risks.

Results and conclusions: 19 RCTs and eight observational studies evaluated issues related to the current objectives. CHC represent an effective and safe treatment in women with any PCOS phenotype. In HA/PCOS patients, any CHC analyzed in this review can be used for symptom relief. For patients with metabolic risk, overweight or moderate IR that does not require metformin, a vaginal contraceptive ring appears to be preferred to oral EE/DRP. In these patients, the combination of CHC and myo-inositol may be more effective in controlling endocrine and metabolic profiles. However, further research is needed to define the optimal duration and to clarify the effects of treatment on long-term metabolic outcomes. Future research should also focus on new CHC.  相似文献   


10.
Objective: To evaluate the effects of ethinyl estradiol-cyproterone acetate (EE-CA) treatment on metabolic and cardiovascular risk factors, and body fat distribution in polycystic ovary syndrome (PCOS) after 6-month treatment. Subjects and methods: Thirty women with PCOS were evaluated before and after 6 months of EE-CA treatment. Anthropometrical measurements, hormonal levels, lipid and glucose profile were evaluated. Body fat thickness in four regions and carotid intima media thickness (IMT) were measured. Interval change in antropometric measurements, glucose and lipid profile, carotid IMT and body fat distribution was evaluated before and after 6-month EE-CA treatment. Results: Ferriman–Gallwey score and serum testosterone levels were significantly decreased after EE-CA treatment (p?<?0.01). No significant effect was detected on insulin resistance, lipid profile and carotid artery IMT. The visceral, subcutaneous and preperitoneal fat thicknesses decreased, and mid-thigh fat thickness increased after treatment period. However, only the alteration in subcutaneous fat thickness achieved a statistical significance (p?<?0.01). Conclusion: The EE-CA is an effective regimen in treatment of hirsutism and menstrual regulation. Although it provides significant decrease in subcutaneous fat thickness after 6-month treatment, it has no beneficial effect with respect to visceral fat thickness, metabolic and cardiovascular risk factors.  相似文献   

11.
Polycystic ovary syndrome (PCOS), a relevant cause of infertility, is a heterogeneous, endocrine disorder affecting up to 10–15% of women in reproductive age. Besides hyperandrogenism, insulin resistance (IR) plays a key role in such syndrome. Insulin-sensitizing drugs, such as Metformin, are effective in treating hyper-insulinemic PCOS patients. Recently, inositols – myo-inositol (MI) and D-chiro-inositol (DCI) – have shown to be an efficient and safe alternative in PCOS management, as both inositol isoforms are able to counteract downstream consequences of insulin resistance. Yet, whereas DCI contributes in mediating insulin activity mainly on non-ovarian tissues, MI displays specific effects on ovary, chiefly by modulating glucose metabolism and FSH-signaling. Moreover, MI may also improve ovarian functions by modulating steroid metabolism through non-insulin-dependent pathways. As DCI and MI activity likely involves different biological mechanisms, both inositol isoforms can be synergistically integrated according to a multitargeted design, by combining MI and DCI in a ratio corresponding to their physiological plasma relative amount (40:1). New experimental and clinical evidence with MI plus DCI evidenced the suitability of such integrated approach, and provided promising results. Further studies need to investigate thoroughly the molecular mechanism and confirm such preliminary data.  相似文献   

12.
Objective: The aim of the study is to analyze daytime changes of prolactin level depending on nutritional status and polycystic ovary syndrome (PCOS).

Study design: One hundred and fifteen (69 normal weight, 21 overweight and 25 obese) diagnosed with PCOS and 77 (37 normal weight, 18 overweight and 22 obese) women – Non-PCOS without concomitant diseases were enrolled. Body mass and height were measured and BMI was calculated. Serum concentrations of FSH, LH, E2, testosterone, TSH and PRL were determined morning 6.00 a.m. after wake. Second measurement of PRL was performed at 4 p.m.

Results: The daytime decrease of prolactin level was higher in PCOS than in Non-PCOS group regardless of nutritional status (normal weight 35.8?±?26.0 vs. 24.3?±?15.3?ng/mL; overweight 28.5?±?25.4 vs. 17.5?±?8.8?ng/mL and obese 23.2?±?21.1 vs. 18.4?±?11.6?ng/ml, respectively). However, in both PCOS and Non-PCOS daytime changes of prolactin level were higher in normal weight than overweight and obese women (35.8?±?26.0 vs. 28.5?±?25.4 vs. 23.2?±?21.1?ng/mL and 24.3?±?15.3 vs. 17.5?±?8.8 vs. 18.4?±?11.6?ng/mL, respectively). The multivariate regression analysis revealed that the daytime changes of prolactin level are proportional to TSH concentration and coexistence of PCOS as well as inversely relative to BMI.

Conclusions: In conclusions, our results suggest that overweight and obesity decreased morning PRL level and impaired its daytime decrease, but coexistence of PCOS enlarged its.  相似文献   

13.
Objective: Due to the complex relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis, the study was planned to measure the kisspeptin levels in polycystic ovary syndrome (PCOS) and to analyze the correlations between kisspeptin and PCOS-related reproductive, metabolic changes.

Methods: The study was designed as a prospective study in Dokuz Eylul University between December 2011 and September 2013. A total of 285 PCOS cases and 162 controls were recruited. After the antropometric measeruments and physcial examination, blood samples were taken for biochemical analysis.

Results: PCOS group’s mean BMI was 24.32?±?3.40 and for the control group, BMI value was 23.44?kg/m2?±?4.08 (p?=?0.351). PCOS patients’ FSH level was 5.10?±?2.01 mIU/L, LH value was 7.75?±?4.31 mIU/mL, LH/FSH ratio was 1.70?±?1.28, DHEAS value was 221.84?±?105.02?mg/dl, total testosterone value was 50.51?±?27.93?ng/ml, free testosterone value was 2.52?±?1.05?pg/ml, SHBG was 63.74?±?45.62?nmol/L, LDL was 102.56?±?23.45?mg/dL, HDL value was 51.36?±?12.15?mg/dL, total cholesterol value was 214.85?±?39.27?mg/dL, triglyceride value was 112.95?±?46.88?mg/dL, Apo A1 value was 171.30?±?35.35?mg/dL, Apo B value was 71.08?±?19.07?mg/dL, Apo B/A1 ratio was 0.42?±?0.14, free androgen index was 13.77?±?14.15, fasting glucose value was 80.68?±?13.80?mg/dL, fasting insulin levels was 14.13?±?9.11 μiU/mL, HOMA-IR index was 2.76?±?2.34, AMH value was 5.93?±?3:33 in ng/ml, and found to be significantly higher (p?Conclusion: In this study, kisspeptin had a positive correlation with LH and leptin levels in PCOS. In fact, the serum levels of kisspeptin and leptin does not differ statistically between PCOS and healthy women. There are limited data in the literature with regard to changes in kisspeptin levels and its relation with metabolic and hormonal disturbances.  相似文献   

14.
15.
Polycystic ovary syndrome (PCOS) is a type of endocrine metabolic disorder with many different consequences to health, most commonly infertility, obesity and insulin resistance. Trivalent chromium (Cr3+) was previously found to improve the metabolic profiles of patients with PCOS. The aim of this study was to explore the effect of Cr on regulating steroidogenic enzymes in adipose tissue. Female BALB/c mice were divided into three groups (n?=?6 per group): the control group, PCOS?+?placebo milk group and PCOS?+?Cr-containing milk group. The dietary intake of Cr significantly decreased fasting blood sugar (FBS) and homeostasis model assessment of insulin resistance levels in the murine model of PCOS. Importantly, we found significant correlations among the levels of Cr, insulin and dehydroepiandrosterone (DHEA). In adipose tissue, decreases in the enzyme expressions of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase, but not of aromatase, were observed. By understanding the role of steroidogenic enzymes in PCOS in normal and pathological states, trace elements may be used as a form of adjunctive therapy in the management of patients with PCOS.  相似文献   

16.
目的探讨多囊卵巢综合征(PCOS)患者基础血清皮质醇水平及其昼夜规律的变化。方法对2008年7月至2010年5月中山大学附属第一医院生殖医学中心63例PCOS患者(21例肥胖和42例非肥胖)及38名月经正常的健康妇女进行空腹8时(基础)及16时血清皮质醇浓度测定,并比较其昼夜规律消失的比例,同时分析影响基础皮质醇水平的可能相关因素。结果肥胖PCOS组、非肥胖PCOS组及健康对照组的基础皮质醇水平分别为(325.7±125.7)nmol/L,(407.6±165.6)nmol/L和(397.4±129.9)nmol/L。其中肥胖PCOS组基础皮质醇水平明显低于健康对照组(P<0.05)。16与8时皮质醇比值,肥胖(0.78±0.54)及非肥胖PCOS组(0.61±0.34)均较健康对照组(0.46±0.20)显著升高(P<0.05)。肥胖PCOS组皮质醇昼夜规律消失率明显高于健康对照组(47.6%vs.10.5%,P<0.05)。相关分析发现基础皮质醇水平与体重指数呈负相关(P<0.05)。结论 PCOS患者(尤其是肥胖PCOS患者)可能存在下丘脑-垂体-肾上腺轴(HPA轴)的功能紊乱。体重指数对皮质醇的代谢以及HPA轴的激活有重要的影响。  相似文献   

17.
杜芳  王继东  姚珍薇 《生殖与避孕》2012,32(11):721-727
目的:探讨再生基因Reg IV在多囊卵巢综合征(PCOS)模型大鼠卵巢组织中的表达情况。方法:采用Poretsky法用胰岛素联合hCG诱导SD大鼠建立PCOS模型,观察大鼠体质量变化及卵巢相对质量;测定血清T、LH、FSH、E2、Ins水平;HE染色观察卵巢形态改变;免疫组织化学方法检测Reg IV蛋白在卵巢组织的定位表达;定量RT-PCR和Western blotting分别检测Reg IV在mRNA水平和蛋白水平的表达。结果:Reg IV分别表达于大鼠颗粒细胞、卵泡膜细胞以及黄体等部位;模型组卵巢中Reg IV mRNA及蛋白表达均低于正常对照组(P<0.05)。结论:Reg IV的表达下调可能与PCOS的发病有关。  相似文献   

18.
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.  相似文献   

19.
Abstract

Objective: The aim of this study was to compare the effect of Diane-35 versus Diane-35?+?metformin on metabolic parameters in Chinese PCOS patients.

Methods: Patients getting individualized life-style modification were treated with Diane-35. Metformin was added according to its indication. Within a 3-month prospective study, metabolic parameters were assessed.

Results: Eighty-three patients were recruited, 45 using Diane-35 and 38 Diane-35 plus metformin. Using Diane-35, triglycerides (TG) (p?<?0.05) and tendencially (p?<?0.1) total cholesterol (TC) increased, but significant positive effects on BMI, high-density lipoprotein cholesterol (HDL-C), and HDL-C/TC ratio were observed. Other lipids and the parameters for glucose metabolism remained unchanged. In the combination group, no negative effect on TG and TC was seen, other lipid fractions improved, as well as BMI, % body fat, and all parameters for glucose metabolism like fasting plasma glucose (FPG), fasting insulin, HOMA-insulin-resistance index, and insulin sensitivity index (ISI), whereby the beneficial effect of metformin got significance compared with Diane-35 for BMI, FPG, and ISI.

Conclusion: With the exception of increasing triglycerides, Diane-35 had no relevant negative effects in the metabolic system. It does not negatively impact the beneficial effects of metformin in lipids and glucose metabolism. Diane-35 plus metformin is effective in improving the metabolic profile of Chinese PCOS patients.  相似文献   

20.
Abstract

Nesfatin-1 is a novel hormon synthesized in hypothalamus and several other specific organs to regulate eating habits, appetite and is thought to be related to ovarian functions. In our study, we aimed to evaluate the nesfatin-1 levels with other metabolic parameters in polycystic ovary syndrome (PCOS), a condition that is known to be related to both ovarian functions and obesity. Study subjects were chosen from the women attended to the Obstetrics and Gynecology Department of Istanbul Bilim University, Avrupa Florence Nightingale Hospital. Thirty-five healthy control subjects and 55 PCOS patients were included. Blood samples were obtained on the 3rd day of the menstrual cycle. Luteinizing hormone (LH), follicle stimulating hormone (FSH), free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), insulin, fasting blood glucose (FBG), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), sex hormone binding globulin (SHBG) levels were measured; homeostatic model assessment-insulin resistance (HOMA-IR) value was calculated. The nesfatin-1 levels were measured by competitive inhibition ELISA method. Due to our results, PCOS patients were having lower nesfatin-1 levels compared to the control group and this was not seemed to be related to body mass index (BMI) levels. This is an important result to be investigated in larger study groups and is related to other metabolic markers.  相似文献   

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