Different impacts of hypertension and diabetes mellitus on all-cause and cardiovascular mortality in community-dwelling older adults: the Rancho Bernardo Study.

OBJECTIVES: Although the prevalence rates of hypertension (HTN) and diabetes mellitus are slowing in some high-income countries, HTN and diabetes mellitus remain as the two major risk factors for atherosclerotic cardiovascular disease (CVD), the leading cause of death in the United States and worldwide. We aimed to observe the association of HTN and diabetes mellitus with all-cause and CVD mortality in older white adults. METHODS: All community-dwelling Rancho Bernardo Study participants who were at least 55 years old and had carefully measured blood pressure and plasma glucose from 75-g oral glucose tolerance test at the baseline visit (1984-1987, n = 2186) were followed up until death or the last clinic visit in 2013 (median 14.3 years, interquartile range 8.4-21.3). RESULTS: In unadjusted analyses, diabetes mellitus was associated with all-cause mortality [hazard ratio 1.40, 95% confidence interval (CI) 1.23-1.60] and CVD mortality (hazard ratio 1.67, 95% CI 1.39-2.00); HTN with all-cause mortality [hazard ratio 1.93 (1.73-2.15)] and CVD mortality [hazard ratio 2.45 (2.10-2.93)]. After adjustment for cardiovascular risk factors, including age, BMI, triglycerides, HDL-cholesterol, smoking, exercise, and alcohol consumption, diabetes mellitus was associated with CVD mortality only (hazard ratio 1.25, P = 0.0213). Conversely, HTN was associated with both all-cause (hazard ratio 1.34, P < 0.0001) and CVD mortality (hazard ratio 1.40, P = 0.0003). Having both diabetes mellitus and HTN was associated with all-cause (hazard ratio 1.38, P = 0.0002) and CVD mortality (hazard ratio 1.70, P < 0.0001). CONCLUSION: We report the novel finding that HTN is more strongly associated with all-cause and CVD mortality than diabetes mellitus. Having both confers a modest increase in the hazards for these types of mortality.

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.

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%, p<0.05). CONCLUSION: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

A genetic risk score is associated with polycystic ovary syndrome-related traits.

STUDY QUESTION: Is a genetic risk score (GRS) associated with polycystic ovary syndrome (PCOS) and its related clinical features? SUMMARY ANSWER: The GRS calculated by genome-wide association studies (GWASs) was significantly associated with PCOS status and its related clinical features. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder and is characterized by oligomenorrhea, hyperandrogenism and polycystic ovary morphology. Although recent GWASs have identified multiple genes associated with PCOS, a comprehensive genetic risk study of these loci with PCOS and related traits (e.g. free testosterone, menstruation number/year and ovarian morphology) has not been performed. STUDY DESIGN, SIZE, DURATION: This study was designed as a cross-sectional case-control study. We recruited 862 women with PCOS and 860 controls. Women with PCOS were divided into four subgroups: (1) oligomenorrhea + hyperandrogenism + polycystic ovary, (2) oligomenorrhea + hyperandrogenism, (3) oligomenorrhea + polycystic ovary and (4) hyperandrogenism + polycystic ovary. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genomic DNA was genotyped for the PCOS susceptibility loci using the HumanOmni1-Quad v1 array. Venous blood was drawn in the early follicular phase to measure baseline metabolic and hormonal parameters. A GRS was calculated by summing the number of risk alleles from 11 single-nucleotide polymorphisms (SNPs) that were identified in previous GWASs on PCOS. A weighted GRS (wGRS) was calculated by multiplying the number of risk alleles for each SNP by its estimated effect (beta) obtained from the association analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The GRS was higher in women with PCOS than in controls (8.8 versus 8.2, P < 0.01) and was significantly associated with PCOS after adjusting for age and BMI. An analysis of GRS quartiles (Q1 = 3-5, Q2 = 6-8, Q3 = 9-11, Q4 = 12-15) revealed that the subjects in the highest quartile showed a remarkable increased risk of PCOS compared with those in the lowest quartile (odds ratio = 6.28, P < 0.001). Free testosterone level, menstruation number per year, ovarian volume and ovarian follicle numbers were significantly associated with the GRS (in all cases, P < 0.01). The wGRS yielded similar results. LIMITATIONS, REASONS FOR CAUTION: We used 11 loci for the calculation of GRS, but a higher number of PCOS risk alleles was reported in previous studies. Therefore, further studies should assess the value of GRS including the additional SNPs related to PCOS. Although a GRS of ≥12 was significantly associated with PCOS, the GRS showed a poor predictive value; therefore, the use of genetic information based on current GWAS data only may present problems. WIDER IMPLICATIONS OF THE FINDINGS: The GRS could be used to identify asymptomatic individuals among people at risk and stratify them into accurate risk categories for the purpose of individualizing treatment approaches, which could potentially improve health outcomes. STUDY FUNDING/COMPETING INTERESTS: None of the authors have any conflicts of interest to declare. No funding was obtained for the study.

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.

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 85(th) percentile and those being overweight and obese with a BMI greater than 85(th) 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 Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes. METHODS: We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed. RESULTS: The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05). CONCLUSIONS: By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS.

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.

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.

Plasma glucose regulation and mortality in Korea: a pooled analysis of three community-based cohort studies.

BACKGROUND: Although diabetes is a well-known risk factor for death, its impact on cancer death is not clearly understood. Furthermore, it remains controversial whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality. We investigated the impact of diabetes or glucose tolerance categories on all cause and cause-specific mortality. METHODS: Mortality analysis was conducted in three population-based cohort studies of 3,801 participants, divided according to fasting plasma glucose (FPG) (normal; stage 1 IFG [5.6≤FPG<6.1 mmol/L]; stage 2 IFG [6.1≤FPG<7.0 mmol/L]; diabetes mellitus [DM]-FPG); or 2-hour glucose after 75 g glucose loading (2hPG) (normal; IGT; DM-2hPG), or a combination of FPG and 2hPG criteria. RESULTS: During a median follow-up of 11.0 years, 474 subjects died from all causes. Hazard ratios (HRs) for all cause death were higher in those with diabetes as defined by either FPG or 2hPG criteria than their normal counterparts (HR, 2.2, 95% confidence interval [CI], 1.6 to 2.9 for DM-FPG; HR, 2.0, 95% CI, 1.5 to 2.7 for DM-2hPG). Similarly, diabetes defined by either FPG or 2hPG was associated with cancer death (HR, 2.9, 95% CI, 1.7 to 5.0; and HR, 2.1, 95% CI, 1.2 to 3.9, respectively). Although neither IFG nor IGT conferred higher risk for death, when combining stage 2 IFG and/or IGT, the risk of all cause death was higher than in subjects with normal glucose regulation (HR, 1.3; 95% CI, 1.0 to 1.6). CONCLUSION: Diabetes is associated with higher risk of death from all causes and cancer. In subjects without diabetes, stage 2 IFG and/or IGT confers increased risk for mortality.

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.

Clinical implications of menstrual cycle length in oligomenorrhoeic young women.

OBJECTIVE: Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea (OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features. DESIGN/PATIENTS/MEASUREMENTS: A total of 1174 young women (aged 19-39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index (ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome (PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40-60 days). RESULTS: In normal-weight women (BMI < 23 kg/m(2)), the degrees of insulin resistance and hyperandrogenaemia are the highest in PCOS and higher in severe OM compared with mild OM. In overweight or obese women, PCOS was more insulin resistant and hyperandrogenaemic, but there was no difference between severe and mild OM. After excluding PCOS, women with severe OM showed a twofold increased risk of metabolic syndrome compared with regular cycling women (odds ratio 2·4, 95% confidence interval 1·1-5·6). By linear regression analysis, a longer menstrual cycle length was associated with ISI after adjustment for age, BMI, metabolic risk factors and testosterone. CONCLUSIONS: Women with a menstrual cycle length over 60 days should be more closely monitored for the metabolic syndrome than women with a menstrual cycle length of 40-60 days, even if they have no PCOS.

Association between extraversion personality and abnormal glucose regulation in young Korean women.

Depression and psychological distress are known to be associated with diabetes development as well as the disease progression including glycemic control and chronic complication, but relationship of personality with diabetes is controversial. We examined whether personality trait and the presence of abnormal glucose regulation (AGR; diabetes and pre-diabetes) are associated in young women. A total of 1,617 young women aged 19-39 years without previously diagnosed diabetes were participated voluntarily. Personality trait was assessed by self-reported questionnaire using the five-factor model (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) consisting of five-point scale ranging from 'strongly disagreeable' to 'strongly agreeable.' Glucose tolerance status was assessed by standard 75-g oral glucose tolerance test. One hundred and eleven women were newly diagnosed with AGR (6.9 %). Among five factors, only extraversion trait was significantly associated with AGR. Multiple linear regression analysis showed significant negative association between extraversion trait and 2-h post-load glucose after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL cholesterol and family history of diabetes (ß = -0.16, P = 0.026). Multiple logistic regression showed extraversion trait having a significant association with the presence of AGR after adjustment for the same covariates (OR 0.97, 95 % CI 0.95-0.99, P = 0.011). The frequency of AGR was significantly increased according to the decrease in extraversion score (P for trend with exact test = 0.047). In conclusion, extraversion may be an important personality trait having a beneficial effect on decreasing the risk of AGR.

Diabetes epidemics in Korea: reappraise nationwide survey of diabetes "diabetes in Korea 2007".

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.

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)-α 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-α, 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 ≥ 25 kg/m(2)) and nonobese (BMI < 25 kg/m(2)) groups. Anthropometric measurements were performed, and serum levels of TNF-α, 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-α 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-α, 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-α levels were not associated with insulin sensitivity, but adiponectin levels were related to insulin sensitivity in women with PCOS.

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≥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 (ß=-0.423, p<0.001) and BMI (ß=-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.

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

OBJECTIVE: 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. DESIGN AND METHODS: One hundred and eighty Korean women aged 16-41 years who were diagnosed with PCOS using the Rotterdam criteria were included. The VAI was derived from a formula using body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol. Visceral adiposity was defined as a visceral fat area (VFA) measuring > 100 cm(2) by CT scanning. Insulin sensitivity was evaluated by insulin-mediated glucose utilization (M value), which was obtained using a euglycemic hyperinsulinemic clamp. RESULTS: The VAI positively correlated with VFA, the visceral-to-subcutaneous fat ratio, and systolic and diastolic blood pressure, and negatively correlated with the M value. In a linear regression analysis, the VAI was an independent determinant of the insulin sensitivity after controlling for age, systolic blood pressure, fasting glucose, fasting insulin, and testosterone levels. In a logistic regression analysis, the VAI odds ratio was 3.5 (95% CI 1.2-9.8) for predicting visceral adiposity after controlling for the various metabolic parameters and testosterone. CONCLUSION: The VAI can replace visceral CT scanning as a marker for visceral adiposity, and it predicts insulin resistance in young women with PCOS.

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.