Risk factor control and cardiovascular events in patients with type 2 diabetes mellitus.

BACKGROUND: Since patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular events, interventions addressing risk factors reduce the incidence of cardiovascular disease (CVD) events. This study aimed to evaluate the difference in the incidence of CVD events according to risk factor control in patients with diabetes with and without cardio-renal disease. METHODS: We analyzed 113,909 patients with diabetes and 290,339 without diabetes using data released by the National Health Insurance Service (NHIS). RESULTS: Among patients with diabetes with four or five poorly controlled risk factors, hazard ratio for CVD events was 1.19 (95% confidence interval [CI], 1.06-1.34) in patients with cardio-renal disease and 2.31 (95% CI, 1.95-2.74) in patients without cardio-renal disease compared to patients with diabetes without risk factors. In subjects with diabetes and cardio-renal disease, patients with four or five poorly controlled risk factors had a higher risk of CVD mortality compared to subjects without risk factors (hazard ratio, 1.64; 95% CI, 1.18-2.30). CONCLUSION: Controlling cardiovascular risk factors reduced the incidence of CVD events in patients with diabetes, especially those without cardio-renal disease. The degree of risk control was strongly associated with CVD mortality in patients with diabetes with baseline cardio-renal disease.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53-6.63) in FT; 1.12 (1.04-1.22) in FAI), FLI (OR 2.68 (95% CI 1.43-5.03) in FT; 1.13 (1.06-1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08-5.21) in FT; 1.5 (1.09-1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

The effect of menopause on cardiovascular risk factors according to body mass index in middle-aged Korean women.

BACKGROUND: Menopausal status and obesity are associated with an increased risk for cardiovascular diseases. However, there are few studies on the effect of menopause on cardiovascular risk factors according to the degree of obesity during the menopausal transition. We aimed to evaluate the effect of menopause on cardiovascular risk factors according to body mass index (BMI) in middle-aged Korean women. METHODS: We analyzed 361 postmenopausal women and 758 premenopausal women (age: 45-55 years) without diabetes mellitus, hypertension, or dyslipidemia, using a cohort database released by the Korean National Health and Nutrition Examination Survey 2016-2018. Subjects were divided into two groups based on BMI. Women who underwent a hysterectomy or were pregnant were excluded from this study. Differences between groups adjusted for age and BMI were assessed. RESULTS: Postmenopausal women (52 ± 2 years) were older than premenopausal women (48 ± 2 years), and BMI did not differ between the two groups (22.8 ± 2.9 vs. 23.0 ± 3.1 kg/m2). After adjustment for age and BMI in total and non-obese subjects (not obese subjects), postmenopausal women exhibited higher hemoglobin A1c and total cholesterol levels than premenopausal women. Subgroup analysis for 138 postmenopausal and 138 age- and BMI-matched premenopausal women showed that postmenopausal women had higher total cholesterol levels than premenopausal women with marginal significance (201 ± 25 vs. 196 ± 27 mg/dL). CONCLUSION: Menopausal status was associated with increased glucose and cholesterol levels independent of age and BMI in middle-aged Korean women. Menopausal status showed a significant relationship with increased total cholesterol levels even after adjusting for age and BMI in non-obese women but not obese women. Therefore, intensive monitoring and treating of lipid status is necessary to prevent cardiovascular events during the menopausal transition, especially in non-obese subjects.

Relationship between age at menarche and metabolic diseases in Korean postmenopausal women: The Korea National Health and Nutrition Examination Survey 2016-2018.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Early menarche may be associated with an increased risk of metabolic diseases such as diabetes and cardiovascular disease. This study aimed to investigate the effect of menarche age and the risk of diabetes and metabolic syndrome in Korean postmenopausal women. METHODS: We analyzed 4,933 postmenopausal women (mean age: 64.7 years) using the Korean National Health and Nutritional Examination Survey 2016-2018. Subjects were divided into three groups according to menarche age (early menarche: ≤ 12 years (n = 451), reference: 13-16 years (n = 3,421), and late menarche: ≥ 17 years (n = 1,061)). Logistic regression analysis was used to estimate the odds ratio (OR) for diabetes and metabolic syndrome. RESULTS: Women with an early menarche age were younger, more educated, and had higher income than the other groups (p-value < 0.001). There were no differences in body mass index, blood pressure, fasting glucose, HbA1c, and cholesterol levels among the three groups. After adjusting for potential confounding factors, early menarche age was significantly associated with the risk of diabetes (OR 1.435, 95% confidence interval (CI): 1.069-1.928). The prevalence of metabolic syndrome in all subjects was 41.1%. After adjusting for potential confounding factors, the OR of metabolic syndrome in the early menarche group was 1.213 (95% CI: 0.971-1.515). CONCLUSION: The risk of diabetes was 1.43 times higher in postmenopausal Korean women with early menarche. Although the risk of metabolic syndrome was not statistically significant, it showed a tendency to increase in the early menarche group. Our results suggest that age at menarche may be helpful in diabetes risk stratification and early interventions for postmenopausal women.

Body mass index and stroke risk among patients with diabetes mellitus in Korea.

BACKGROUND: Obesity and diabetes mellitus (DM) are both associated with cardiovascular disease. This study aimed to evaluate the association between body mass index (BMI) and stroke risk among patients with DM in Korea since relatively few studies have analyzed this area in detail. METHODS: We analyzed a total of 56,051 DM patients aged >30 years from the Korean National Health Insurance Service Cohort who had undergone at least one national health examination between 2002 and 2012. BMI scores were divided into six categories, while hazard ratios for stroke were calculated using Cox proportional hazard models. RESULTS: Overall stroke risk was positively associated with BMI for both men and women. For ischemic stroke, the risk was positively associated with BMI in women. However, for me, only patients with the highest BMI were at increased risk compared with patients with a BMI of 20-22.4 kg/m2. For hemorrhagic stroke, the risk was significantly associated with BMI with a U-shaped association in men. In women, only patients with the lowest BMI had an increased risk of hemorrhagic stroke compared with patients that have a BMI of 20-22.4 kg/m2. CONCLUSION: BMI was positively associated with the overall risk of stroke among DM patients in Korea. The risk of ischemic stroke was higher in obese patients compared to overweight or normal-weight patients. However, the risk of hemorrhagic stroke was higher in slimmer patients compared with overweight or obese patients.

Waist circumference and mortality or cardiovascular events in a general Korean population.

BACKGROUND: Obesity is associated with cardiovascular diseases and is a risk factor for all-cause mortality. Until now, the associations between abdominal obesity and mortality or cardiovascular disease (CVD) incidence have not been conclusive. We aimed to evaluate the associations between waist circumference (WC) and mortality or CVD incidence in a general Korean population. METHODS: We analyzed a total of 204,068 adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2018 in the Korean National Health Insurance Service Cohort. WC was divided into five categories (< 80, 80-84.9, 85-89.9, 90-94.9, ≥ 95 cm). Hazard ratios for death and CVD incidence were calculated using Cox proportional hazards models. RESULTS: In men, WC and overall mortality showed a reverse J-shaped association. In women, the association between WC and overall mortality was not significant. For both men and women, WC was not associated with the risk of cardiovascular mortality. Contrary to the mortality trend, CVD incidence was positively associated with WC in both men and women, and the risk of the CVD incidence was the lowest in subjects with a WC < 80 cm. CONCLUSIONS: WC exhibited a significant J-shaped association with overall mortality in men, where subjects who had central obesity showed a lower rate of mortality than those in the lowest or highest WC group. The risk of incident CVD showed a positive association with central obesity, where the lowest risk was observed for subjects in the lowest WC group in a general Korean population.

Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study.

BACKGROUND: Reduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. METHODS: We analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated. RESULTS: In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. CONCLUSIONS: Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

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.

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 anti-Müllerian 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.

Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes.

Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) on Han Chinese, Korean, and European populations identified multiple PCOS-susceptible loci; however, only a few studies reported the association of susceptibility genes with disease phenotypic traits. This cross-sectional study aimed to investigate the association between PCOS susceptibility genes from GWAS and disease-related clinical features. A total of 1,810 reproductive-aged women were recruited, including 927 control women and 883 women with PCOS, diagnosed based on the European Society for Human Reproduction and Embryology criteria. Genomic DNA was extracted and genotyped, and a Bonferroni test was performed to determine the association between 12 independent SNPs and the clinical features of PCOS. In women with PCOS, rs11031006, nearest to FSHB, was significantly associated with free testosterone (P = 1.94 × 10-3) and luteinizing hormone (P = 1.96 × 10-3) levels. The menstruation number per year, ovarian follicular number, ovarian volume, and insulin sensitivity index were not associated with any SNP. In the control group, no SNPs were associated with any PCOS traits. Collectively, our results suggest that FSHB may play an important role in the development and progression of PCOS.

Vitamin D receptor and binding protein polymorphisms in women with polycystic ovary syndrome: a case control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, characterized by hyperandrogenism, oligomenorrhea, polycystic ovary morphology, and insulin resistance. Vitamin D deficiency and vitamin D receptor (VDR)/vitamin D binding protein (VDBP) gene variants could play an important role in susceptibility to PCOS and contribute to metabolic disturbances and menstrual dysfunction. We aimed to investigate the associations of VDR gene and VDBP gene polymorphisms with PCOS susceptibility and to elucidate the impacts of these polymorphisms on the hormonal and metabolic parameters of PCOS. METHODS: We recruited 432 women with PCOS and 927 controls. Polymorphisms in the VDR gene (VDR Fok-I, Cdx2, Apa-I, and Bsm-I) and VDBP gene (VDBP rs4588, rs7041, and rs22822679) were genotyped. A 75-g oral glucose tolerance test was performed. RESULTS: The distributions of genotypes and allele frequencies in VDR and VDBP genes did not differ between PCOS and control. In women with PCOS, compared to the VDR Fok-I GG genotype, the VDR Fok-I AG genotype was significantly associated with increased levels of total testosterone (ß = 5.537, P = 0.005). Compared to the VDR Cdx2 AC genotype, the VDR Cdx2 CC genotype was associated with increased levels of fasting insulin and HOMA-IR in women with PCOS, however, the associations were not statistically significant. CONCLUSIONS: This finding indicates that genetic variations in VDR and VDBP were not associated with increased risk for PCOS. In contrast, the VDR Fok-I polymorphism was associated with testosterone level and the Cdx2 polymorphism with insulin sensitivity in PCOS. However, the Cdx2 polymorphism was not significantly associated with increased insulin and insulin sensitivity in women with PCOS after multiple linear regression.

Insulin resistance is associated with hirsutism in unselected reproductive-aged women.

OBJECTIVE: Hirsutism affects 5%-10% of reproductive-aged women worldwide and exhibits clinical importance as a cutaneous manifestation of underlying hyperandrogenism. Racial and genetic factors play roles in manifestation of hirsutism, and the prevalence of hirsutism seems to be low in East Asians. However, the reference value of the modified Ferriman-Gallwey (mFG) score to diagnose hirsutism and the prevalence of hirsutism have not been determined in Korean populations to date. We aimed to investigate the distribution of the mFG score and establish its reference value for defining hirsutism and to examine its relationship with metabolic and reproductive traits in reproductive-aged Korean women. DESIGN, PATIENTS AND MEASUREMENTS: We enrolled 2139 female volunteers of reproductive age (15-39 years). We recorded mFG scores from 0 to 4 on 9 different body locations (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back and thighs). Hirsutism was defined as >95th percentile of mFG score. In addition, a 75-g oral glucose tolerance test was performed, and the homoeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: The mFG values of the 50th, 75th, 90th and 95th percentiles were 0, 1, 4 and 6, respectively. Therefore, the mFG score was indicative of hirsutism when the score was 6 or greater, which represents the 95th percentile. In the correlation analysis, total testosterone, free testosterone, fasting plasma insulin and HOMA-IR were positively correlated with mFG score (all Ps <0.05). Multiple linear regression analysis revealed that HOMA-IR (ß = 0.081) was positively associated with mFG score after adjustments for age, body mass index, total testosterone and the number of menses per year (P < 0.001). CONCLUSIONS: In conclusion, setting the 95th percentile of the mFG score as normal, the reference value to define hirsutism was 6 in reproductive-aged Korean women. HOMA-IR was positively associated with the mFG score even after adjustment for biochemical hyperandrogenism.

Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration.

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in thyroid fine needle aspiration (FNA) is a challenging category. The malignancy risk is different by multiple factors and subsequent management strategy is inconclusive. Therefore, we analyzed the malignancy risk of AUS/FLUS according to radiological and clinical features. A total of 687 nodules that had been initially diagnosed as AUS/FLUS were retrospectively reviewed from 6365 thyroid FNAs between 2011 and 2014. The ultrasonographic (US) features were categorized using the Korean Thyroid Imaging Reporting and Data System. Radiological and clinical features were compared according to the second FNA results or histologically confirmed results from surgery. Repeat FNA was performed on 248 (36%) nodules, and 49 (7%) nodules underwent immediate surgery. Among the 248 nodules subjected to repeated FNA, 49 (20%) nodules were diagnosed again as AUS/FLUS, 123 (50%) were found to be benign, and 47 (19%) were diagnosed as follicular neoplasm, suspicious for malignancy or malignant. Among histologically confirmed nodules, the US features were more unfavorable in malignant nodules, and hypo- or anechogenicity was associated with a higher risk of malignancy after adjusting for age, size, and other US features (P < 0.01). In conclusion, we observed that malignant nodules tended to show unfavorable US features, especially hypo- or anechogenicity. Age, sex, and thyroid function were not significantly associated with malignancy risk. We also found out that malignancy risk was not different between the group which underwent immediate operation following the AUS/FLUS diagnosis and the group which underwent repeated FNA after the initial diagnosis.

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.

Associations between body mass index and mortality or cardiovascular events in a general Korean population.

BACKGROUND/OBJECTIVES: The relationship between body mass index (BMI) and mortality remains controversial. Furthermore, the association between BMI and cardiovascular events (CVE) is not conclusive and may differ by ethnicity. We aimed to estimate the associations between the BMI and mortality or cardiovascular disease in a general Korean population. SUBJECTS/METHODS: This study was based on a sample cohort database released by the Korean National Health Insurance Service. We analyzed a total of 415,796 adults older than 30 years of age who had undergone a national health examination at least once from 2002 to 2012. Hazard ratios for death and cardiovascular events were calculated using Cox proportional hazards models. RESULTS: For both men and women, BMI and overall mortality showed a U-shaped association, with the lowest mortality rate among those with a BMI of 25-27.4 kg/m2. Compared with them, subjects with a BMI ≥ 30kg/m2, men with a BMI < 25 kg/m2, and women with a BMI < 22.5 kg/m2 showed significantly higher overall mortality. Additionally, men with a BMI < 22.5 kg/m2 and women with a BMI < 20 kg/m2 displayed an increased risk of cardiovascular mortality. Unlike the mortality trend, the CVD events trend showed a linearly positive association. The risk of a CVE was the lowest in men with a BMI ranging from 20 to 22.4 kg/m2 and in women with a BMI < 20 kg/m2. CONCLUSIONS: The BMI showed a U-shaped association with overall mortality, where slightly obese subjects showed the lowest rate of mortality. The CVE exhibited a linear association with the BMI, where the lowest risk was observed for normal weight subjects in a general Korean population.

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.

Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism.

Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: anxiety, N2: angry hostility, N3: depression, N4: self-consciousness, N5: impulsivity and N6: vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10-9). Notable genes with suggestive associations (P<1.0 × 10-6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.

Polycystic ovary morphology is associated with insulin resistance in women with polycystic ovary syndrome.

BACKGROUND/OBJECTIVES: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic anovulation, hyperandrogenism, polycystic ovary morphology (PCOM) and metabolic disturbances including insulin resistance and type 2 diabetes mellitus. Although insulin resistance could be associated with PCOM, recent studies have shown controversial results. The aim of this study was to determine the relationship between PCOM and insulin resistance. SUBJECTS/METHODS: This was a cross-sectional clinical study. A total of 679 women with PCOS who were diagnosed using the National Institute of Child Health and Human Disease (NICHD) criteria and 272 control women were analysed. We measured fasting glucose and insulin levels, 75 g oral glucose tolerance test-derived glucose and insulin levels, testosterone levels, ovarian volume and follicle number. RESULTS: Polycystic ovary morphology was described in 543 women (80.0%) with PCOS. Women with PCOS had significantly higher 2 hours postload glucose, fasting and 2 hours postload insulin levels, ovarian volume, ovarian follicle numbers and lower insulin sensitivity compared with those of the controls (all P<.01). In women with PCOS, ovarian volume and ovarian follicle number were negatively associated with the quantitative insulin sensitivity check index after adjusting for age, body mass index and total testosterone; however, this association was not observed in the controls. In the logistic regression analysis, increased ovarian follicle number was associated with decreased insulin sensitivity in women with PCOS. CONCLUSIONS: In PCOS, enlarged ovarian volume and follicle excess were associated with insulin resistance, and the number of ovarian follicles could be a predictor of insulin resistance.

Insulin resistance according to ß-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and ß-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. METHODS: We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased ß-cell function was defined as>75th percentile for the HOMA-F in control women. RESULTS: Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05). Women with PCOS and increased ß-cell function showed lower Stumvoll index values than the matched controls (P<0.05). The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05). The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05). CONCLUSIONS: Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and ß-cell function. ß-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

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 (ß = 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.