Yeon-Ah Sung

The visceral adiposity index as a predictor of insulin resistance in young women with polycystic ovary syndrome

Visceral fat accumulation is more strongly related to insulin resistance than to excess total adiposity. The visceral adiposity index (VAI) has recently been suggested as an indicator of the visceral adiposity measured by magnetic resonance imaging. To evaluate whether the VAI could replace visceral computed tomography (CT) scanning and predict insulin resistance in young women with polycystic ovary syndrome (PCOS) was presented.

Optimal hemoglobin A1C Cutoff Value for Diagnosing type 2 diabetes mellitus in Korean adults

Commonly used tests for the diagnosis of diabetes include measurements of fasting plasma glucose levels and the oral glucose tolerance test (OGTT). Recently, a hemoglobin A1C (A1C) level of 6.5% has been included as a criterion for diabetes diagnosis by the American Diabetes Association. We aimed to determine appropriate A1C cutoff values for identifying patients with diabetes or prediabetes, including impaired glucose tolerance and impaired fasting glucose among Korean adults and to determine whether these cutoffs vary according to age. We recruited 4616 adults without a history of diabetes from 10 university hospitals. A 75-g OGTT and A1C sampling were performed in all examinees. Pointwise area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the A1C cutoff. An A1C threshold of 6.1% proved to be the optimal limit for diagnosing diabetes, with 63.8% sensitivity and 88.1% specificity. The cutoff value increased with age (5.9% in 18-39 years, 6.2% in 40-64 years, and 6.4% in older than 65 years) and were similar for men and women. An A1C cutoff of 5.7% had reasonable sensitivity (48.6%) and specificity (65.7%) for the identification of prediabetes. Further prospective studies should be carried out to determine whether the application of age-specific diagnostic criteria is appropriate.

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.

Serum C-Reactive Protein Levels in Normal-Weight Polycystic Ovary Syndrome

Background/Aims Serum levels of highly sensitive C-reactive protein (hsCRP), a vascular inflammatory marker, may predict the development of cardiovascular disease (CVD) and type 2 diabetes. Women with polycystic ovary syndrome (PCOS) are at greater risk for type 2 diabetes and CVD. The aim of this study was to compare hsCRP levels between normal weight women with PCOS and controls with a normal menstrual cycle and to determine the factors associated with serum hsCRP levels. Methods Thirty-nine lean PCOS patients and 24 healthy, regular cycling women were enrolled in this study. We performed anthropometric measurements, fat computed tomography (CT), and blood sampling to determine blood chemistry and levels of hsCRP, gonadotropins, testosterone, and sex-hormone binding globulin. We also conducted 75-g oral glucose-tolerance test and euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Results Serum hsCRP concentrations were higher in women with PCOS than in women with regular mensturation. However, this difference was no longer significant after adjusting for body mass index (BMI). hsCRP levels were correlated with waist circumference (r=0.46, p<0.01), BMI (r=0.46, p<0.01), visceral fat area (r=0.45, p<0.01), and systolic (r=0.42, p<0.05) and diastolic blood pressure (r=0.39, p<0.05). hsCRP also tended to be negatively associated with insulin-mediated glucose uptake (IMGU) (r=-0.31, p=0.07). A multiple regression analysis revealed that BMI (β=0.29, p<0.05), systolic blood pressure (β=0.39, p<0.01), and IMGU (β=-0.31, p<0.05) predicted serum hsCRP levels in women with PCOS. Conclusions PCOS by itself does not seem to be associated with increased hsCRP levels, whereas known CVD risk factors affect serum hsCRP levels in PCOS.

Hyperandrogenemia is implicated in both the metabolic and reproductive morbidities of polycystic ovary syndrome

OBJECTIVE To determine the features of polycystic ovary syndrome (PCOS) that are implicated in the associated reproductive and metabolic morbidities. DESIGN Cross-sectional case-control study. SETTING Academic medical setting. PATIENT(S) A total of 1,062 women with PCOS and 1,887 women without PCOS. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Physical examination including hirsutism scoring, biochemical and hormone measurements, ovarian ultrasound, and a 75-g oral glucose tolerance test to measure glucose and insulin levels. RESULT(S) A factor analysis identified four dominant factors in women with PCOS. These factors were interpreted as follows: [1] metabolic and hyperandrogenemia factor, [2] oligomenorrhea and hyperandrogenemia factor, [3] blood pressure factor, and [4] ovarian morphology factor. In women with PCOS, hyperandrogenemia was a significant predictor of metabolic syndrome after adjusting for age, body mass index, and insulin resistance in the regression analysis. CONCLUSION(S) A factor analysis identified multiple factors that are responsible for the abnormalities associated with PCOS. Hyperandrogenemia was a common underlying feature of the metabolic and reproductive abnormalities in women with PCOS but not in women without PCOS.

Genome-wide association study identifies GYS2 as a novel genetic factor for polycystic ovary syndrome through obesity-related condition.

To investigate the role of genetic predisposition in the pathogenesis of polycystic ovary syndrome (PCOS) in relation to obesity, we performed a genome-wide association study of PCOS in Koreans (n=1741). PCOS is a heterogeneous endocrinal disorder of uncertain etiology. Obesity is one of the well-known risk factors for PCOS. Genome-wide association study. Women with or without PCOS. A total of 1881 samples were genotyped using Illumina HumanOmni1 Quad v1 and processed by R packages. The PCOS patients were divided into two subgroups according to PCOS diagnostic criteria (Rotterdam and National Institutes of Health (NIH)). For PCOS-associated loci in the two definitions, we successfully confirmed significant associations of GYS2 for body mass index in the discovery stage. We further replicated pleiotropic associations of GYS2 in a childhood obesity study (n=482) and in a gestational diabetes study (n=1710), respectively. Our study provides a preliminary framework upon diverse genetic effects underlying PCOS in Korean women. A newly identified GYS2 gene as a predisposing factor of PCOS might expand understanding of the biological pathways in metabolic and endocrine regulation.

Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome

STUDY QUESTION Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)? SUMMARY ANSWER We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women. WHAT IS KNOWN ALREADY PCOS is a highly complex disorder with significant contributions from both genetic and environmental factors. Previous genome-wide association studies (GWAS) in the Han Chinese population identified several risk loci for PCOS. However, GWAS studies on PCOS remain very few. The aim of this study was to identify novel markers of susceptibility to PCOS through GWAS. STUDY DESIGN, SIZE, DURATION A two-stage GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS cases and 946 controls. The second stage (replication study) included 249 PCOS cases and 778 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising signals selected from the discovery stage were tested for their association with PCOS. MAIN RESULTS AND THE ROLE OF CHANCE One novel locus with genome-wide significance and seven moderately associated loci for PCOS were identified. The strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 × 10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12, 3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 × 10(-6)-6.43 × 10(-5)). The strongest signal was located upstream of KHDRBS3, which is associated with telomerase activity, and could drive PCOS and related phenotypes. LIMITATIONS, REASONS FOR CAUTION The limitation of our study is the modest sample size used in the replication cohort. The limited sample size may contribute to a lack of statistical power to detect an association or show a trend in severity. WIDER IMPLICATIONS OF THE FINDINGS Our findings provide new insight into the genetics and biological pathways of PCOS and could contribute to the early diagnosis and prevention of metabolic and reproductive morbidities. STUDY FUNDING/COMPETING INTERESTS This work was supported in part by the grant from the Korea Centers for Disease Control and Prevention (2009-E00591-00). The work was also supported by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors has any conflict of interest to declare.

Sleep Disorder and Cardiovascular Risk Factors among Patients with Type 2 Diabetes Mellitus

Background/Aims Sleep disorder (SD) is associated with an increased risk of cardiovascular disease and is more prevalent among individuals with type 2 diabetes mellitus. These health problems not only frequently coexist but also exacerbate each other. We conducted a cross-sectional study to estimate the prevalence of SD among diabetic patients and to investigate the relationship between SD and cardiovascular risk among these patients. Methods We recruited 784 patients with type 2 diabetes and conducted a self-administered questionnaire. We assessed sleep quality using the Pittsburgh Sleep Quality Index and the risk of obstructive sleep apnea (OSA) using the Berlin Questionnaire. Additional information included blood pressure and metabolic profiles. Results Of the 784 diabetic patients, 301 (38.4%) patients had poor sleep quality, and 124 (15.8%) were at high risk for OSA. Patients at increased risk for OSA were more obese; they also had higher blood pressure, fasting plasma insulin levels, insulin resistance assessed by homeostasis model assessment (HOMA-IR), and serum triglycerides levels (p < 0.05). The frequency of risk for OSA was higher among obese patients compared with non-obese patients (34.8% vs. 9.4%, p < 0.05). Logistic regression analysis revealed that male sex and bone mass index were independent predictors of risk for OSA. Conclusions SD was prevalent among type 2 diabetic patients, and OSA could aggravate their risk for cardiovascular disease. Clinical treatment of these patients should include evaluation and intervention for SD.

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.

111/121 diplotype of Calpain-10 is associated with the risk of polycystic ovary syndrome in Korean women

We investigated whether the CAPN-10 polymorphism UCSNP-43, -19, and -63 contribute, either individually or as haplotype/diplotype, to the susceptibility of polycystic ovary syndrome (PCOS) or related quantitative traits in Korean women. Our data showed that 111 haplotype and 111/121 and 111/111 diplotypes in the CAPN-10 gene were associated with a significantly increased risk of PCOS, and 112 haplotype and 121/121 and 112/122 diplotypes were associated with decreased risk of PCOS in the Korean population.