The Association of Ovarian Reserve with Exposure to Bisphenol A and Phthalate in Reproductive-aged Women

Background@#Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. @*Methods@#This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. @*Results@#Urinary bisphenol A (BLA) level was significantly higher in the DOR group with antiMüllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05).Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). @*Conclusion@#BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women.

Association of Vitamin D Deficiency with Diabetic Nephropathy

Background@#Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM. @*Methods@#This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay. @*Results@#The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables. @*Conclusion@#Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

Association between cadmium and anti-Mullerian hormone in premenopausal women at particular ages

BACKGROUND: Anti-Mullerian hormone (AMH) in women is secreted by granulosa cells of antral follicles. AMH appears to be a very stable marker for ovarian function. It may be used to diagnosis cases of premature ovarian failure, polycystic ovary syndrome (PCOS), and ovarian tumors. It has been suggested that cadmium exposure can reduce female fecundity. The purpose of this study was to investigate whether environmental exposure to cadmium was associated with alterations in AMH with regards to age. METHODS: In a cross-sectional study, the data of premenopausal women living in Seoul, ranging from 30 to 45 of age was collected. The study included a total of 283 women who completed serum AMH and whole blood cadmium assessments. Linear regression analyses were used in order to examine the association between cadmium and AMH. Given that age was the strongest confounder in both cadmium and AMH concentrations, we stratified subjects by 5 years old and analyzed their data. RESULTS: Geometric mean concentrations of blood cadmium and AMH were 0.97 μg/L and 3.02 ng/ml, respectively. Total association between cadmium and AMH was statistically significant (adjusted coefficient = − 0.34 (0.15), p = 0.02). After stratification, the only age group with a negative association between cadmium and AMH were the women raging between 30 and 35 years (adjusted coefficient = − 0.43 (0.18), p = 0.01). CONCLUSIONS: The results of this study suggest that environmental exposure to cadmium may alter the AMH level of premenopausal women, depending on their age group.

Blood cadmium and volume of uterine fibroids in premenopausal women

BACKGROUND: A number of studies have found associations between heavy metals and uterine fibroids, but the results are inconsistent. Here, we conducted this research to demonstrate the relationships between blood heavy metal concentrations and uterine fibroid volume as well as the rate of uterine fibroid presence. METHODS: In a cross-sectional study, we collected data from 308 premenopausal women aged 30–49 years in Seoul; uterine fibroids are ascertained by past history of myomectomy and pelvic ultrasonography. In the analytic phase, we first analyzed the presence of the fibroids and the concentrations of heavy metals via logistic regression. In subgroup analysis, we used simple and multiple linear regression analyses to examine the associations between heavy metals and uterine fibroid volume. RESULTS: There was no connection between the heavy metal concentrations and the presence of uterine fibroids, but the odds of women having fibroids were higher with three particular metals. In subgroup analysis, the association between blood cadmium concentrations and uterine fibroid volume was statistically significant (adjusted beta coefficient = 2.22, 95% confidential interval: 0.06–4.37). In contrast, blood mercury and lead concentrations were not significantly associated with uterine fibroid volume. CONCLUSIONS: Our findings are the first that we know to report the association of blood cadmium concentrations with the volume of uterine fibroids. We expect that our findings will be used as evidence for supporting policies to improve premenopausal Korean women's health.

Differentiation between polycystic ovary syndrome and polycystic ovarian morphology by means of an anti-Müllerian hormone cutoff value

BACKGROUND/AIMS: Although increased serum anti-Müllerian hormone (AMH) level has been suggested to be a surrogate marker of polycystic ovarian morphology (PCOM), its association with polycystic ovary syndrome (PCOS) is controversial, and its diagnostic value has not been determined. We aimed to observe the relationship between the AMH level and PCOS phenotypes and to determine the optimal cutoff value of AMH for the diagnosis of PCOS in young Korean women. METHODS: We recruited 207 women with PCOS (120 with PCOM and 87 without PCOM) and 220 regular cycling women with normoandrogenemia (100 with PCOM and 120 without PCOM). Subjects underwent testing at a single outpatient visit. Serum AMH level was measured. RESULTS: Women with PCOS had higher serum AMH levels than did regular cycling women with normoandrogenemia (p < 0.05). Women with PCOM had higher serum AMH levels than women without PCOM, regardless of PCOS status (p < 0.05). The optimal AMH cutoff value for the diagnosis of PCOS was 10.0 ng/mL (71% sensitivity, 93% specificity). Serum AMH was an independent determinant of total testosterone after adjustment for age, body mass index, and the number of menses/year (β = 0.31, p < 0.01). An association between AMH and hyperandrogenism was only observed in women with PCOS, and it was independent of the presence of PCOM. CONCLUSION: The serum AMH level can be useful for the diagnosis of PCOS at any age less than 40 years, and the optimal cutoff value for the diagnosis of PCOS identified in this study of young Korean women was 10.0 ng/mL.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

PURPOSE: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. MATERIALS AND METHODS: We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). RESULTS: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

PURPOSE: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. MATERIALS AND METHODS: We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). RESULTS: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

Insulin Initiation in Insulin-Naive Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study

BACKGROUND: The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs). METHODS: This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] > or =7.0%) who had been on OHAs for > or =3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice. RESULTS: A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event. CONCLUSION: In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Incidentally Discovered Aldosterone and Cortisol Cosecreting Adrenal Cortical Adenoma / 이화의대지

A substantial proportion of adrenal incidentalomas demonstrates subtle hormonal hypersecretion; however, adenomas that cosecrete aldosterone and cortisol are rare. We here report a case of an adrenal mass that was incidentally detected on a computed tomography scan in a 57-year-old man. The patient had a 10-year history of diabetes mellitus and a 5-year history of hypertension. Evaluation revealed hyperaldosteronemia with an elevated plasma aldosterone-to-renin ratio, hypokalemia, unsuppressed cortisol after dexamethasone administration, and elevated urinary free cortisol concentration. The appearance of the right adrenalectomy specimen indicated adrenal adenoma. Postoperatively, the blood glucose and blood pressure control improved and the urinary cortisol and aldosterone-to-renin ratio normalized. A complete endocrine evaluation in patients with incidentally discovered adrenal masses should be performed, even if the patient has a long-standing history of hypertension and diabetes, to avoid any postoperative adrenal crises.

Increased Epicardial Adipose Tissue Thickness in Type 2 Diabetes Mellitus and Obesity

BACKGROUND: Epicardial adipose tissue (EAT) is suggested to play an important role in the progression of metabolic syndrome. We aimed to establish a simple method to measure EAT and examine the differences in EAT thickness according to the presence of type 2 diabetes mellitus or obesity. METHODS: A total of 94 patients (42.6% type 2 diabetes mellitus, 53.2% obese, mean age 61+/-13) who underwent multidetector computed tomography were enrolled. Thickness of EAT was measured on the parasternal short and horizontal long axis view. Epicardial fat area (EFA) was measured at the level of left main coronary artery (LMCA). RESULTS: All EAT thicknesses were correlated with EFA at the LMCA level (r=0.235 to 0.613, all Ps<0.05), and EAT thickness in the left atrioventricular groove (LAVG) had the highest correlation coefficient (r=0.613). EFA, and EAT thicknesses in the LAVG and the left ventricular apex were higher in the group with type 2 diabetes mellitus than in the group without type 2 diabetes mellitus when adjusted only for body mass index. When adjusted only for type 2 diabetes mellitus, EFA, and EAT thicknesses in the LAVG and the right atrioventricular groove were higher in obese group than in nonobese group. CONCLUSION: In conclusion, EAT thickness can be easily measured and represent EFA. EAT thickness, especially in LAVG, was higher in groups with type 2 diabetes mellitus and obesity independently. These findings implicate that EAT thickness may be a useful indicator for type 2 diabetes mellitus and obesity.

Decreased Insulin Secretion in Women with Previous Gestational Diabetes Mellitus / 이화의대지

OBJECTIVES: Gestational diabetes mellitus (GDM) affects 2%-4% of the all pregnant women, and it is a major risk factor for development of type 2 DM. We performed this cross-sectional study to determine whether there were defects in insulin secretory capacity or insulin sensitivity in women with previous GDM. METHODS: On 6-8 weeks after delivery, 75 g oral glucose tolerance test was performed in 36 women with previous GDM and 19 non-pregnant control women matched with age and weight. Intravenous glucose tolerance test was performed on 10-14 weeks after delivery. Insulin secretory capacity measured as the acute insulin response to glucose (AIRg) and insulin sensitivity as minimal model derived sensitivity index (S(I)) were obtained. AIRg x S(I) (beta-cell disposition index) was used as an index of beta-cell function. RESULTS: Women with previous GDM were classified into normal glucose tolerance (postpartum-NGT, n=19) and impaired glucose tolerance (postpartum-IGT, n=17). Postpartum fasting glucose levels were significantly higher in postpartum-IGT compared to postpartum-NGT and control (P<0.05). AIRg x S(I) was significantly lower in postpartum-IGT compared to control (P<0.05). S(I) was lower in postpartum-NGT and postpartum-IGT compared to control, but the difference did not have the statistical significance. Frequency of parental history of type 2 diabetes was significantly greater in postpartum-IGT compared to postpartum-NGT (P<0.05). CONCLUSION: Women with previous GDM showed impaired insulin secretion although their glucose tolerance states were restored to normal. It suggests impaired early insulin secretion may be a major pathophysiologic factor for development of type 2 DM, and this defect may be genetically determined.

Epidemiology and Diagnostic Criteria of Polycystic Ovary Syndrome / 임상당뇨병

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by oligomenorrhea, hyperandrogenism and polycystic ovaries. The prevalence of PCOS varies between 6% and 10% depending on the diagnostic criteria and the ethnicity. Diagnosis of PCOS relies on a combination of clinical, biological and ultrasound criteria that are used worldwide in different variations. Few studies have extensively examined reproductive and metabolic characteristics and hyperandrogenism in Korean women. Despite the paucity of these studies, they are critical for ascertaining PCOS diagnostic criteria for this population. This review addresses the epidemiology and diagnostic criteria of PCOS specifically for Korean women.

Metabolic effects of polycystic ovary syndrome in adolescents

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS. METHODS: Anthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI)-matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile. RESULTS: Hemoglobin, gamma-glutamyl transferase (r-GT), total cholesterol, low-density lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%. CONCLUSION: PCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents.

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 +/- 8.9 years; body mass index, 24.6 +/- 3.2 kg/m2). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 x 10(-6)), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 x 10(-7), Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

FTO Gene Variants Are Associated with PCOS Susceptibility and Hyperandrogenemia in Young Korean Women

BACKGROUND: The fat mass and obesity-associated (FTO) gene is associated with obesity and type 2 diabetes mellitus. Obesity and insulin resistance are also common features of polycystic ovary syndrome (PCOS). Therefore, the FTO gene might be a candidate gene for PCOS susceptibility. The aim of the present study was to evaluate the effects of FTO gene variants on PCOS susceptibility and metabolic and reproductive hormonal parameters. METHODS: We recruited 432 women with PCOS (24+/-5 years) and 927 healthy women with regular menstrual cycles (27+/-5 years) and performed a case-control association study. We genotyped the single nucleotide polymorphisms rs1421085, rs17817449, and rs8050136 in the FTO gene and collected metabolic and hormonal measurements. RESULTS: Logistic regression revealed that the G/G genotype (rs1421085, 1.6%), the C/C genotype (rs17817449, 1.6%), and the A/A genotype (rs8050136, 1.6%) were strongly associated with an increased risk of PCOS (odds ratio, 2.551 to 2.559; all P<0.05). The strengths of these associations were attenuated after adjusting for age and BMI. The women with these genotypes were more obese and exhibited higher free androgen indices (P<0.05) and higher free testosterone levels (P=0.053 to 0.063) compared to the other genotypes. However the significant differences disappeared after adjusting for body mass index (BMI). When we analyzed the women with PCOS and the control groups separately, there were no significant differences in the metabolic and reproductive hormonal parameters according to the FTO gene variants. CONCLUSION: The rs1421085, rs17817449, and rs8050136 variants of the FTO gene were associated with PCOS susceptibility and hyperandrogenemia in young Korean women. These associations may be mediated through an effect of BMI.

Comparison of the Body Adiposity Index to Body Mass Index in Korean Women

PURPOSE: Obesity is a major public health issue and is associated with many metabolic abnormalities. Consequently, the assessment of obesity is very important. A new measurement, the body adiposity index (BAI), has recently been proposed to provide valid estimates of body fat percentages. The objective of this study was to compare the BAI and body mass index (BMI) as measurements of body adiposity and metabolic risk. MATERIALS AND METHODS: This was a cross-sectional analysis performed on Korean women. The weight, height, and hip circumferences of 2950 women (mean age 25+/-5 years old, 18-39 years) were measured, and their BMI and BAI [hip circumference (cm)/height (m)(1.5)-18] values were calculated. Bioelectric impedance analysis was used to evaluate body fat content. Glucose tolerance status was assessed with a 75-g oral glucose tolerance test, and insulin sensitivity was estimated with the insulin sensitivity index. RESULTS: BMI was more significantly correlated with fat mass and fat percentage. Additionally, BMI was also more significantly associated with metabolic parameters, including fasting glucose, post-load 2-h glucose, fasting insulin, post-load 2-h insulin, triglycerides, and high density lipoprotein cholesterol than BAI. Receiver operating characteristic curve analysis revealed that BMI was a better tool for predicting body fat percentage than BAI. Insulin sensitivity and metabolic syndrome were more significantly associated with BMI than with BAI. CONCLUSION: In Korean women, the current BMI-based classifications for obesity might be superior to BAI-based measurements for determining obesity and predicting metabolic risk.

Obesity: Introduction / 대한내과학회지

Obesity is defined as abnormal or excessive fat accumulation that presents a risk to a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Therefore, obesity is associated with decreases in life expectancy. Also weight loss of 5-10% is associated with clinically significant health benefits. In Korea, a person with a body mass index of 25 kg/m2 or more is considered obese. In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended screening all adults for obesity and USPSTF advised that clinicians offer or refer patients with obesity to intensive, multicomponent behavioral interventions. In Korea, management of obesity 2010 recommendation was published but there is no recommendation about screening for obesity. Because of the increasing prevalence of obesity, new recommendations on screening and efficient treatment for obesity and overweight are needed in Korea.

Is Insulin Resistance an Intrinsic Defect in Asian Polycystic Ovary Syndrome?

PURPOSE: Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and obesity is known to worsen insulin resistance. Many metabolic consequences of PCOS are similar to those of obesity; therefore, defining the cause of insulin resistance in women can be difficult. Our objective was to clarify the factors contributing to insulin resistance in PCOS. MATERIALS AND METHODS: We consecutively recruited 144 women with PCOS [age: 26+/-5 yr, body mass index, body mass index (BMI): 24.4+/-4.0 kg/m2] and 145 controls (age: 25+/-5 yr, BMI: 23.0+/-3.6 kg/m2), and divided them into overweight/obese (ow/ob, BMI > or =23 kg/m2) and lean (BMI <23 kg/m2) groups. Anthropometric measures and a 75-g oral glucose tolerance test were performed, and insulin sensitivity index (ISI) was calculated as an index of insulin sensitivity. Factors predictive of ISI were determined using regression analysis. RESULTS: ISI was significantly lower in both lean and ow/ob women with PCOS compared to BMI-matched controls (p<0.05). Increasing BMI by 1 kg/m2 decreased ISI by 0.169 in PCOS patients (p<0.05) and by 0.238 in controls (p<0.05); there was no significant difference between these groups. In lean PCOS patients and lean controls, BMI had no effect on ISI. Multiple regression analysis revealed that PCOS status (beta=-0.423, p<0.001) and BMI (beta=-0.375, p<0.001) were significantly associated with ISI. CONCLUSION: Insulin resistance is an intrinsic defect of PCOS, and a high BMI could exacerbate insulin resistance in all women, irrespective of whether they have PCOS.

Adipokines, insulin-like growth factor binding protein-3 levels, and insulin sensitivity in women with polycystic ovary syndrome

BACKGROUND/AIMS: Many women with polycystic ovary syndrome (PCOS) exhibit insulin resistance. Adipose tissue plays an important role in insulin resistance, and adipokines including tumor necrosis factor (TNF)-alpha and adiponectin are altered in PCOS. Insulin-like growth factor binding protein-3 (IGFBP-3), alone or in conjunction with other adipokines, is also associated with insulin resistance. We evaluated the effects of TNF-alpha, adiponectin, and IGFBP-3 on insulin sensitivity and the relationships among these proteins in women with PCOS. METHODS: We recruited 40 women with PCOS and 40 age- and body mass index (BMI)-matched regular cycling women (controls). The women were divided into obese (BMI > or = 25 kg/m2) and nonobese (BMI < 25 kg/m2) groups. Anthropometric measurements were performed, and serum levels of TNF-alpha, adiponectin, and IGFBP-3 were determined. Insulin sensitivity was estimated using the metabolic clearance rate (MCR) of glucose calculated from the oral glucose tolerance test. RESULTS: Serum levels of TNF-alpha and IGFBP-3 did not differ between the PCOS and control groups, but adiponectin levels in the PCOS group were lower than those in control women in the nonobese group (p < 0.05). TNF-alpha, adiponectin, and IGFBP-3 levels were not correlated with each other in women with PCOS, but a significant positive correlation was observed between adiponectin levels and MCR (p < 0.05). Multiple regression analysis revealed that adiponectin levels were significantly associated with insulin sensitivity (p < 0.05) in women with PCOS. CONCLUSIONS: IGFBP-3 and TNF-alpha levels were not associated with insulin sensitivity, but adiponectin levels were related to insulin sensitivity in women with PCOS.

Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women

BACKGROUND/AIMS: The existence of an association between thyrotropin (thyroid stimulating hormone, TSH) levels and metabolic derangement in euthyroid subjects is controversial. We examined the association between high normal TSH levels and metabolic syndrome in healthy young women. METHODS: The study recruited 2,760 young female volunteers (age, 18 to 39 years) with TSH levels in the normal range (0.3 to 4.5 mU/L). We defined metabolic syndrome using the 2007 International Diabetes Federation criteria. Using a TSH level of 2.5 mU/L as an upper reference limit, as recommended by the National Academy of Clinical Biochemistry, we divided the subjects into high-(n = 453) and low-TSH groups (n = 2,307). RESULTS: The prevalence of metabolic syndrome was significantly higher in the high-TSH group than in the low-TSH group (7.5% vs. 4.8%, p = 0.016). Central obesity (22.3% vs. 17.3%, p = 0.012) and hypertriglyceridemia (8.0% vs. 4.2%, p = 0.0007) were significantly more frequent in the high-TSH group than in the low-TSH group. Waist circumference, systolic and diastolic blood pressure, and triglycerides were significantly associated with the TSH level after adjusting for age and body mass index (BMI). Subjects in the high-TSH group had a 2-fold greater risk of metabolic syndrome than subjects in the low-TSH group after adjusting for age and BMI (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2). CONCLUSIONS: Healthy young women with TSH levels > 2.5 mU/L should be assessed for the presence of metabolic syndrome, even if their TSH levels are in the normal range.