Low muscle mass and risk of type 2 diabetes in middle-aged and older adults: findings from the KoGES.

AIMS/HYPOTHESIS: Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations. METHODS: We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/m2 or a waist circumference of ≥90 cm for men and ≥85 cm for women. RESULTS: During a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/m2. The mean MMI for men and women was 32.1% and 26.0%, respectively. There was an inverse association between MMI and the risk of type 2 diabetes. Multivariate-adjusted HRs for the risk of developing type 2 diabetes were 2.05 (95% CI 1.73, 2.43), 1.39 (95% CI 1.17, 1.66) and 1.0 from the lowest to highest sex-specific MMI tertile, with an HR of 1.35 (95% CI 1.26, 1.45) per SD decline in MMI. Further adjustments for fat mass, waist circumference and BMI as categorical variables did not modify the relationship (each p < 0.01). In BMI-stratified analyses, the population-attributable fraction of the lowest tertile of MMI for developing type 2 diabetes was increased by 11.9% in the non-obese group and 19.7% in the obese group. CONCLUSIONS/INTERPRETATION: Low muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.

Gender- and age-group-specific associations between physical performance and bone mineral density, falls, and osteoporotic fractures in Koreans: the Chungju Metabolic Disease Cohort study.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Genetic association of APOA5 and APOE with metabolic syndrome and their interaction with health-related behavior in Korean men.

BACKGROUND: Genome-wide association studies have been used extensively to identify genetic variants linked to metabolic syndrome (MetS), but most of them have been conducted in non-Asian populations. This study aimed to evaluate the association between MetS and previously studied single nucleotide polymorphisms (SNPs), and their interaction with health-related behavior in Korean men. METHODS: Seventeen SNPs were genotyped and their association with MetS and its components was tested in 1193 men who enrolled in the study at Seoul National University Hospital. RESULTS: We found that rs662799 near APOA5 and rs769450 in APOE had significant association with MetS and its components. The SNP rs662799 was associated with increased risk of MetS, elevated triglyceride (TG) and low levels of high-density lipoprotein, while rs769450 was associated with a decreased risk of TG. The SNPs showed interactions between alcohol drinking and physical activity, and TG levels in Korean men. CONCLUSIONS: We have identified the genetic association and environmental interaction for MetS in Korean men. These results suggest that a strategy of prevention and treatment should be tailored to personal genotype and the population.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.

BACKGROUND: Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. METHODS: Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. RESULTS: In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10(-8); OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. CONCLUSIONS: Our findings provide new insights into the genetic architecture underlying OF in East Asians.

Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study.

In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

Retinoic acid receptor-related orphan receptor α-induced activation of adenosine monophosphate-activated protein kinase results in attenuation of hepatic steatosis.

UNLABELLED: There is increasing evidence that the retinoic acid receptor-related orphan receptor α (RORα) plays an important role in the regulation of metabolic pathways, particularly of fatty acid and cholesterol metabolism; however, the role of RORα in the regulation of hepatic lipogenesis has not been studied. Here, we report that RORα attenuates hepatic steatosis, probably via activation of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) and repression of the liver X receptor α (LXRα). First, RORα and its activator, cholesterol sulfate (CS), induced phosphorylation of AMPK, which was accompanied by the activation of serine-threonine kinase liver kinase B1 (LKB1). Second, the activation of RORα, either by transient transfection or CS treatment, decreased the TO901317-induced transcriptional expression of LXRα and its downstream target genes, such as the sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase. RORα interacted physically with LXRα and inhibited the LXRα response element in the promoter of LXRα, indicating that RORα interrupts the autoregulatory activation loop of LXRα. Third, infection with adenovirus encoding RORα suppressed the lipid accumulation that had been induced by a free-fatty-acid mixture in cultured cells. Furthermore, we observed that the level of expression of the RORα protein was decreased in the liver of mice that were fed a high-fat diet. Restoration of RORα via tail-vein injection of adenovirus (Ad)-RORα decreased the high-fat-diet-induced hepatic steatosis. Finally, we synthesized thiourea derivatives that activated RORα, thereby inducing activation of AMPK and repression of LXRα. These compounds decreased hepatic triglyceride levels and lipid droplets in the high-fat-diet-fed mice. CONCLUSION: We found that RORα induced activation of AMPK and inhibition of the lipogenic function of LXRα, which may be key phenomena that provide the beneficial effects of RORα against hepatic steatosis.

The Effect of Early Intensive Insulin Therapy on Body Fat Distribution and ß-Cell Function in Newly Diagnosed Type 2 Diabetes.

OBJECTIVES: The aim of this study was to evaluate the effects of early intensive insulin therapy on body fat distribution, lean body mass and ß-cell function in patients with newly diagnosed type 2 diabetes. METHODS: Thirty-eight subjects with newly diagnosed type 2 diabetes participated in a 12-week course of intensive insulin therapy. Patients were administered a 75 g oral glucose tolerance test (OGTT), underwent measurement of visceral and subcutaneous adipose tissues (VAT and SAT) using computed tomography and appendicular skeletal muscle (ASM) mass was assessed using dual-energy X-ray absorptiometry. RESULTS: After intensive insulin therapy, fasting plasma glucose and HbA1c levels decreased. Homeostasis model assessment (HOMA)-B, the insulinogenic index, and the C-peptide-to-glucose area under the curve (AUC) ratio increased. The insulin sensitivity index and the glucose AUC decreased after 12 weeks. The body composition analysis revealed that the VAT and the ratio of VAT to SAT decreased, whereas body weight and total fat mass increased nonsignificantly. The ASM/weight and skeletal muscle mass index increased. The restoration of ß-cell function, as identified by HOMA-B, the insulinogenic index, and the C-peptide-to-glucose AUC ratio, was correlated with the changes in VAT when controlled for age and gender. In multiple regression analyses, the decrease in VAT was shown to independently contribute to improved HbA1c over the study period, after adjusting for confounding factors. CONCLUSIONS: These results suggest that a shift in fat distribution from visceral to subcutaneous fat after early intensive insulin therapy is associated with improvements in glycemic control and ß-cell function in patients with newly diagnosed type 2 diabetes.

A genome-wide by PM10 exposure interaction study for blood pressure in Korean adults.

Blood pressure (BP) is a typical complex trait, and the genetic susceptibility of individuals to changes in BP induced by air pollution exposure is different. Although interactions of exposure to air pollutants with several candidate genes have been identified, genome-wide interaction studies (GWISs) are needed to understand the association between them with BP. Therefore, we aimed to discover the unique genetic loci for BP that interact with exposure to air pollutants in Korean adults. We ultimately included 1868 participants in the discovery step and classified them into groups of those with low-to-moderate exposure and high exposure to average annual concentration of particulate matter with an aerodynamic diameter ≤ 10 µm (PM10). Because none of the single nucleotide polymorphisms (SNPs) achieved a genome-wide level of significance of pint < 5 × 10-8 for either systolic BP (SBP) or diastolic BP (DBP), we considered the top 10 ranking SNPs for each BP trait. To validate these suggestive SNPs, we finally selected six genetic variants for SBP and five variants for DBP, respectively. In a replication result for SBP, only one SNP (rs12914147) located in an intergenic region of the NR2F2 showed a significant interaction. We also identified several genetic susceptibility loci (e.g., CHST11, TEK, and ITGA1) implicated in candidate mechanisms such as inflammation and oxidative stress in the discovery step, although their interaction effects were not replicated. Our study reports the first GWIS finding to our knowledge, and the association between exposure to PM10 and BP levels may be determined in part by several newly discovered genetic suggestive loci, including NR2F2.

A whole-genome reference panel of 14,393 individuals for East Asian populations accelerates discovery of rare functional variants.

Underrepresentation of non-European (EUR) populations hinders growth of global precision medicine. Resources such as imputation reference panels that match the study population are necessary to find low-frequency variants with substantial effects. We created a reference panel consisting of 14,393 whole-genome sequences including more than 11,000 Asian individuals. Genome-wide association studies were conducted using the reference panel and a population-specific genotype array of 72,298 subjects for eight phenotypes. This panel yields improved imputation accuracy of rare and low-frequency variants within East Asian populations compared with the largest reference panel. Thirty-nine previously unidentified associations were found, and more than half of the variants were East Asian specific. We discovered genes with rare protein-altering variants, including LTBP1 for height and GPR75 for body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type-specific effects. We suggest that this dataset will add to the potential value of Asian precision medicine.

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea.

We prospectively examined the association between type 2 diabetes mellitus (T2DM) progression and common T2DM-risk gene variants in 870 non-diabetic participants in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit-associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene) rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data and metabolic parameters were obtained at baseline and year 4. Pancreatic ß cell function was assessed by the homeostasis model assessment index of ß cells (HOMA-ß). After 4 years, 137 subjects developed T2DM (15.7%). A significant association was found in the variant of KCNQ1 rs2237892, whereas the SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C-allele carriers of KCNQ1 conferred a significantly increased risk for T2DM compared with the T/T genotype, independently of clinical risk factors (odds ratio=2.61, 95% confidence intervals=1.02-6.69, P=0.04). Although no differences were observed at baseline among the KCNQ1 variants, HOMA-ß levels by year 4 were significantly lower in the C-allele carriers after controlling for metabolic parameters. The genetic variations in KCNQ1 are associated with future development of T2DM in Koreans, which might be mediated by differences in insulin secretory function.

Continuous glucose monitoring: current clinical use.

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans.

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.

A Genome-Wide Association Study on Abdominal Adiposity-Related Traits in Adult Korean Men.

INTRODUCTION: Although previous genome-wide association studies (GWASs) have identified genetic susceptibility loci for abdominal adiposity, GWASs on Asian samples remain scarce. Therefore, we performed a GWAS for abdominal adipose tissue depots in a Korean population. METHODS: A total of 1,937 Korean men were included in the study. Areas of abdominal fat were quantified by computed tomography. We performed a GWAS analysis under an additive model, and a replication study was conducted on 480 additional Korean adult men. RESULTS: In the discovery step, we identified a total of 10 single-nucleotide polymorphisms (SNPs) associated with adiposity indicators (p < 1 × 10-5). The top SNP, rs1028014, for visceral adipose tissue (VAT) was located in the ZMAT4 gene and remained significant after adjustment for body mass index (BMI). Three additional SNPs were also associated with VAT-adj-BMI and located within the SLC26A10, FAM155A, and COL4A1-COL4A2 genes, respectively. In addition, we identified a SNP (rs4668224) of the MYO3B gene for visceral-to-subcutaneous fat ratio. For subcutaneous adipose tissue and total adipose tissue, two (rs6585735 and rs363527) and three SNPs (rs1487892, rs9357565, and rs1985358) were found, respectively. Overall, eight SNPs were used in the replication study; however, none of the SNPs reached our level of significance for replication (p < 0.0063). Nevertheless, rs4773144 of COL4A1-COL4A2 for VAT-adj-BMI was the most interesting SNP identified in previous GWASs for coronary artery disease (based on the same risk allele "G"), along with functional effects. CONCLUSION: This study suggests for the first time that an SNP (rs4773144) of COL4A1-COL4A2 may contribute to the increase in VAT level, especially in adult Korean men.

Early onset female pattern hair loss: A case-control study for analyzing clinical features and genetic variants.

BACKGROUND: Female pattern hair loss (FPHL), the most common cause of alopecia in adult women, is classified into two subtypes: early onset and late onset (or postmenopausal). Little is known about the clinical features and genetic characteristics of early onset female pattern hair loss (eFPHL). OBJECTIVES: To investigate the clinical features and genetic characteristics of eFPHL. METHODS: Patients with eFPHL and controls without eFPHL were prospectively recruited. The demographic and clinical features were collected. Single nucleotide polymorphisms (SNPs) located around the selected 30 candidate genes potentially associated with eFPHL were evaluated. RESULTS: eFPHL patients (n = 63) manifested a decreased hair shaft density and cross-sectional area of the hair shaft compared to the control group (n = 341). eFPHL is associated with androgen-related features, including scalp greasiness, folliculitis, hirsutism, and polycystic ovary syndrome. Scalp pain and itching have been reported more frequently in patients with eFPHL. Forty-nine SNPs located around PPARGC1A, ABCC4, CYP11B2, FSHB, and CYP19A1 were found to be significant for eFPHL, including two PPARGC1A-associated SNPs: rs186530605 and rs192713767 (p = 3.94 × 10-11). CONCLUSIONS: This study provided clinical features and genetic variants for eFPHL, which could provide insight into the underlying pathologic etiology. Considering the limited number of patients, a large-scale study is required in the future.

Transforming growth factor-ß induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells.

Pancreatic duct cells are considered a potential source of ß-cell regeneration, and transforming growth factor-ß (TGF-ß) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF-ß1, pancreatic duct cells were isolated from three brain-dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF-ß1. We analyzed the characteristics of the cultured cells, the TGF-ß1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF-ß1 treatment. After TGF-ß1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. ß cell-specific transcription factors including PDX-1, Beta2/NeuroD, Ist-1, and NGN3 were markedly suppressed and the rate of transdifferentiation into ß cells was also suppressed. Genomic and proteomic analyses suggested that TGF-ß1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF-ß1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into ß cells. Our results are the first report of TGF-ß1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells.

Identifying metabolically obese but normal-weight (MONW) individuals in a nondiabetic Korean population: the Chungju Metabolic disease Cohort (CMC) study.

OBJECTIVE: To investigate the prevalence and identify the phenotype of individuals suspected to be metabolically obese but normal weight (MONW). DESIGN AND SUBJECTS: Eight thousand nine hundred and eighty-seven nondiabetic subjects aged over 40 years were selected from the Chungju Metabolic disease Cohort study performed in 2003-2006 in Korea. Those within the highest quartile in the homeostasis model assessment of insulin resistance (HOMA-IR) with a normal body mass index (BMI) between 18·5 and 23 kg/m(2) were classified as MONW. MEASUREMENTS: Data on anthropometry, lipid profiles and HOMA-IR values were analysed. RESULTS: The prevalence of MONW was 14·2% for men and 12·9% for women amongst normal-weight subjects. Multiple logistic regression analysis showed that total cholesterol (TC) levels over 5·17 mm (odds ratio, OR = 1·481; 95% confidence intervals, CI 1·086-2·021), triglyceride (TG) levels over 1·69 mm (OR = 1·507; 95% CI 1·093-2·077) and high-density lipoprotein-cholesterol levels lower than 1·03 mm (OR = 1·580; 95% CI 1·053-2·371) independently had higher odds of diagnosing MONW amongst men. For women, a BMI over 21·5 kg/m(2) (OR = 1·405; 95% CI 1·034-1·909), TC levels over 5·17 mm (OR = 1·524; 95% CI 1·112-2·090) and TG levels over 1·69 mm (OR = 1·799; 95% CI 1·302-2·487) were independently associated with a diagnosis of MONW. CONCLUSIONS: More than 10% of normal-weight subjects were classed as MONW in this cohort. Identification of these subjects based on lipid profiles could aid in the early detection of a high risk group of developing cardiometabolic diseases.

Association of serum bone morphogenetic protein 4 levels with obesity and metabolic syndrome in non-diabetic individuals.

Bone morphogenetic protein 4 (BMP-4) is involved in the earliest stages of adipocyte differentiation and is recognized as an adipogenic factor for white adipose tissue. The association of serum BMP-4 levels with anthropometric and metabolic parameters has not been previously studied. We aimed to explore the relationship of serum BMP-4 levels with obesity and metabolic syndrome. Serum BMP-4 levels were measured in 104 non-diabetic individuals from the Chungju Metabolic Disease Cohort Study. Anthropometric measurements and components of metabolic syndrome were assessed in all patients. Serum BMP-4 levels were significantly increased in individuals with obesity or metabolic syndrome. After adjusting for age and gender, serum BMP-4 levels were positively correlated with body mass index, waist circumference (WC), waist-to-hip ratio, fasting plasma insulin, homeostasis model assessment index, and triglycerides and were negatively correlated with high-density lipoprotein (HDL) cholesterol. Among these parameters, WC and HDL cholesterol were found to be independent contributing factors for serum BMP-4 levels. Serum BMP-4 levels were also significantly higher in subjects with positive diagnostic criteria for each component of metabolic syndrome. The area under the receiver operating characteristic curve for BMP-4 was 0.661 (P = 0.022, 95% CI = 0.528 to 0.794) and the cut-off value was 2.84 pg/mL. This is the first demonstration that serum BMP-4 levels are associated with adiposity, insulin resistance, and the presence of metabolic syndrome. Whether BMP-4 may be involved in the pathogenesis of obesity and metabolic syndrome deserves further investigation.

Prevalence and associated factors of diabetic retinopathy in rural Korea: the Chungju metabolic disease cohort study.

This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, cross-sectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.

The relationship between thyroid nodules and uterine fibroids.

Previous studies suggested that estrogen might have an important role in thyroid nodule formation. Besides, it was recently reported that women with uterine fibroids, which estrogen has effects on, had an increased incidence of thyroid nodules. Our study was to identify the relationship between uterine fibroids and thyroid nodules and to find the factors that may have influences on the occurrence of thyroid nodules. We reviewed the records of 1144 participants who attended health check-ups from 2005 to 2008. Evaluated clinical variables included the size and number of thyroid nodules, presence of uterine fibroids, menopausal status, BMI, smoking, alcohol, medication status, serum levels of cholesterol, LH, FSH, and estradiol. A total of 925 participants were included and 163 (17.6%) subjects had thyroid nodules and uterine fibroids simultaneously. A significant association between both diseases existed (P=0.010), and closer relationship was observed in premenopausal women (n=445, P=0.001). In univariate analysis of systemic E2 level and the incidence of thyroid nodule in premenopausal women, systemic E2 levels had inverse correlation with the incidence of thyroid nodules (P=0.024, OR=0.631, CI: 0.424-0.940). In multivariate logistic regression analysis, older age and the presence of uterine fibroids were the independent factors for the presence of thyroid nodules. Our study suggested that uterine fibroids in women were definitely associated with thyroid nodules and estrogen might have a pivotal role in occurrence of both uterine fibroids and thyroid nodules.

Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus.

A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.