Jin Taek Kim

Prevalence and risk factors of osteoporosis in Korea: A community-based cohort study with lumbar spine and hip bone mineral density

PURPOSE To investigate bone mineral density (BMD) profiles, osteoporosis prevalence and risk factors in a community-based cohort in Korea. METHODS The present study is a cross-sectional study. The study population consisted of 1,547 men and 1991 women aged 40 years and older with BMD measurements using central dual energy X-ray absorptiometry from a prospective community-based cohort. The data were compared with other ethnic groups. Risk factors related to osteoporosis were analyzed. RESULTS Crude prevalence of osteoporosis in the whole subjects (40-79 years old) was 13.1% for men and 24.3% for women by WHO criteria, at any site among lumbar spine, femoral neck or total hip. Standardized prevalence of osteoporosis between age of 50 and 79 at lumbar spine, femoral neck and total hip was 12.9%, 1.3% and 0.7% in men and 24.0%, 5.7% and 5.6% in women, respectively. The mean BMD of studied female subjects after age of 50 was not significantly different from that of Chinese but significantly lower than that of Japanese, non-Hispanic whites, non-Hispanic blacks and Mexican Americans. Risk of osteoporosis was significantly associated with the presence of past fracture history (OR, 1.45; 95% CI, 1.08-1.94), smoking> or =1 pack/day (OR, 1.63; 95% CI, 1.01-2.62), menarche after age of 16 (OR, 1.46; 95% CI, 1.14-1.87), last delivery after age of 30 (OR, 1.58; 95% CI, 1.20-2.09), more than three offspring (OR, 1.42; 95% CI, 1.07-1.89), post-menopause status (OR, 7.32; 95% CI, 3.05-17.6), more than 17 years since menopause (OR, 1.53; 95% CI, 1.10-2.14), regular exercise of two to three times per week (OR, 0.40; 95% CI, 0.18-0.89), monthly income above 500,000 won per household (OR, 0.64; 95% CI, 0.45-0.92), college graduate (OR, 0.29; 95% CI, 0.13-0.63) and calcium intake> or =627.5 mg/day (OR, 0.65; 95% CI, 0.43-0.98) after adjusting for age and BMI. CONCLUSION The BMD and osteoporosis prevalence of Koreans are presented. Risk of osteoporosis was significantly associated with fracture history, smoking, reproductive history, regular exercise, income level, education background and calcium intake.

Changes in Hepatic Gene Expression upon Oral Administration of Taurine-Conjugated Ursodeoxycholic Acid in ob/ob Mice

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05), whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis.

Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea

Background To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects. Methods We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009. Results A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users. Conclusion We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

Novel cell‐based assay reveals associations of circulating serum AhR‐ligands with metabolic syndrome and mitochondrial dysfunction

Serum concentrations of environmental pollutants have been positively correlated with diabetes and metabolic syndrome in epidemiologic studies. In turn, abnormal mitochondrial function has been associated with the diseases. The relationships between these variables, however, have not been studied. We developed novel cell-based aryl hydrocarbon receptor (AhR) agonist bioassay system without solvent extraction process and analyzed whether low-dose circulating AhR ligands in human serum are associated with parameters of metabolic syndrome and mitochondrial function. Serum AhR ligand activities were measured as serum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (sTCDDeq) in pM using 10 μL human sera from 97 Korean participants (47 with glucose intolerance and 50 matched controls, average age of 46.6 ± 9.9 years, 53 male and 45 female). sTCDDeq were higher in participants with glucose intolerance than normal controls and were positively associated (P < 0.01) with obesity, blood pressure, serum triglyceride, and fasting glucose, but not with HDL-cholesterol. Body mass index was in a positive linear relationship with serum AhR ligands in healthy participants. When myoblast cells were incubated with human sera, ATP generating power of mitochondria became impaired in an AhR ligand concentration-dependent manner. Our results support that circulating AhR ligands may directly reduce mitochondrial function in tissues, leading to weight gain, glucose intolerance, and metabolic syndrome. Our rapid cell-based assay using minute volume of human serum may provide one of the best monitoring systems for circulating AhR ligands, good clinical biomarkers for the progress of disease and therapeutic efficacy.

Gender Differences in Diagnostic Values of Visceral Fat Area and Waist Circumference for Predicting Metabolic Syndrome in Koreans

Abdominal fat accumulation is known to be strongly implicated in development of metabolic syndrome (MetS). We examined diagnostic values of obesity-related parameters in 95 men and 185 women, and we determined optimal cutoff values of visceral fat area (VFA) and waist circumference (WC) for predicting the presence of multiple non-adipose components of MetS. Receiver operating characteristic (ROC) curve analysis revealed that VFA was the best indicator of MetS. WC and VFA exhibited similar diagnostic values for men and postmenopausal women, whereas WC was inferior to VFA for premenopausal women (area under ROC curve of VFA and WC was 0.76 and 0.52, respectively; P < 0.001). Optimal cutoff points of VFA and WC for predicting MetS were 136 cm2 and 89 cm in men and 95 cm2 and 82 cm in women, respectively. Subjects with VFA and WC above these cutoff values exhibited increased insulin resistance and increased carotid intima-media thickness. In conclusion, WC has a diagnostic value similar to VFA for predicting MetS in men and postmenopausal women, but not in premenopausal women. Further studies are necessary to develop a simple clinical parameter that reflects visceral fat in premenopausal women.

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody

Background Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. Methods We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. Results The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. Conclusion The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Comparison of regional body composition and its relation with cardiometabolic risk between BMI-matched young and old subjects

OBJECTIVE Difference in regional body composition between young and old people may be related with differential cardiometabolic risks. We investigated regional body composition in BMI-matched young and old subjects to compare its relation with cardiometabolic risk. METHODS We recruited 1:3 gender- and BMI-matched 86 young subjects (mean age 27.3 ± 2.9 years) and 258 older subjects (75.6 ± 8.2 years) from a community. Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) and muscle area at mid-thigh level were evaluated by computed tomography. Fat depots in the gynoid area and lower extremity were measured by dual energy X-ray absorptiometry. Adiponectin, retinol binding protein-4 (RBP-4), and C-reactive protein (CRP) concentrations, pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured for cardiometabolic risk. RESULTS VAT was greater in older subjects while SAT was almost the same, resulting in twice higher VAT/SAT ratio in older men and women (1.03 ± 0.37 and 0.57 ± 0.18) than younger counterparts (0.55 ± 0.24 and 0.23 ± 0.23) (both P < 0.01). Fat mass in the gynoid area and lower extremity was smaller in older subjects than younger subjects. The VAT correlated with adiponectin level negatively and RBP-4 level positively while gynoid fat correlated with them in opposite direction. The CRP levels negatively correlated with mid-thigh muscle in older subjects. Older subjects had higher PWV and lower ABI compared to BMI-matched younger counterparts. CONCLUSION In conclusion, older adults in this cohort had increased visceral fat and decreased gynoid and lower extremity fat, along with less muscle mass. These findings may help explain the worse cardiometabolic profiles in the elderly who have the same BMI as the young.

Polymorphisms of ADIPOR1 and ADIPOR2 are associated with phenotypes of type 2 diabetes in Koreans.

Objective  Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) are considered as candidate genes for type 2 diabetes because they mediate the metabolic effects of adiponectin on target tissues. We investigated whether common polymorphisms of ADIPOR1 and ADIPOR2 are associated with type 2 diabetes or its related phenotypes in Koreans.

Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea

Background There are no published data regarding fracture risk in type 2 diabetic patients in Korea. In this study, we compared the fracture incidence and risk of osteoporosis of type 2 diabetic female patients with those in a non-diabetic hypertensive cohort. Methods The incidence of fracture in a type 2 diabetic cohort was compared with that in a non-diabetic hypertensive cohort over the course of 7 years. Female type 2 diabetic and non-diabetic hypertensive patients who visited Eulji General Hospital outpatient clinic from January 2004 to April 2004 were assigned to the diabetic cohort and the non-diabetic hypertensive cohort, respectively. Surveys on fracture event, use of anti-osteoporosis medications, and bone mineral density were performed. Results The number of fractures was 88 in the female diabetic cohort (n=1,268, 60.6±11.5 years) and 57 in the female non-diabetic hypertensive cohort (n=1,014, 61.4±11.7 years). The RR in the diabetic cohort was 1.38 (P=0.064; 95% confidence interval [CI], 0.98 to 1.94) when adjusted for age. Diabetic patients with microvascular complications (61.0%) showed a higher RR of 1.81 (P=0.014; 95% CI, 1.13 to 2.92) compared with those without these complications. The prevalence of osteoporosis was comparable between the groups, while use of anti-osteoporosis medication was more common in the diabetic cohort (12.8%) than in the hypertensive cohort (4.5%) (P<0.001). Conclusion In our study, a higher fracture risk was observed in female type 2 diabetics with microvascular complications. Special concern for this risk group is warranted.

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy.

Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity‐related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell‐based arylhydrocarbon receptor (AhR)‐dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.