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Background: We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).Methods: We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM.Methods: In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1,862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥40 was considered indicative of high distress. Individuals with high distress (n=589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, longer duration of diabetes, and higher homeostatic model assessment for insulin resistance level (all p

This study investigated the antidiabetic outcomes after gastrectomy with long-limb RY reconstruction (LRYR) and the prognostic factors for remission after 1 year in patients with type 2 diabetes (T2DM) and gastric cancer. In 25 Koreans with T2DM and gastric cancer, plasma glucose and insulin levels were measured during a 75 g oral glucose tolerance test, before and 1 week after gastrectomy with LRYR. Patients were examined after 1 year and we defined glycemic control as "remission" when the HbA1c level after 1 year was6.0% without medication. One year after surgery, 12 patients achieved HbA1c6.0% without medication. Among the preoperative indices, the duration of diabetes was shorter in the remission group than that in the non-remission group (median 2.0 [0-6.5] years vs 7.0 [4.5-10.0] years, P = .023). At 1 week after surgery, significant improvements in fasting, 30 minutes, 60 minutes, 90 minutes stimulated glucose levels and insulin resistance (HOMA-IR and Matsuda index) were found only in the remission group. The multivariable logistic regression analysis results showed that higher 30 minutes stimulated glucose level and HOMA-IR index at 1 week after surgery were independent factors for lower odds of 1-year diabetes remission. Shorter duration of diabetes and early postoperative improvements in 30 minutes stimulated glucose level and HOMA-IR were important determinants of long-term antidiabetic outcomes after gastrectomy with LRYR in patients with T2DM and gastric cancer.

Herein, we investigate whether statin treatment as primary prevention reduces cardiovascular outcomes in elderly Asian patients.Data were obtained from the Korean National Health Insurance Service-Senior Cohort database (n = 558,147). A total of 81,729 elderly patients (≥75 years) without clinically recognized atherosclerotic cardiovascular disease (CVD) were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to the end of 2012. New statin users (n = 3670) were matched on the basis of the propensity score in a 1:2 ratio with non-users. Incidences of myocardial infarction, ischemic stroke, and death from CVD were compared using the Cox proportional hazards model.The risk of cardiovascular death was significantly reduced in the statin treatment group compared with the non-user group (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.29 to 0.40; p 0.001). This effect was observed in both patient groups with and without diabetes. In patients with diabetes, the HR for statin use was 0.85 (95% CI 0.55 to 1.33) for myocardial infarction and 0.75 (95% CI 0.60 to 0.93) for ischemic stroke. In participants without diabetes, the HR of statin use was 0.95 (95% CI 0.73 to 1.24) for myocardial infarction and 1.13 (95% CI 1.01 to 1.26) for ischemic stroke. The presence of hypertension was also a significant factor in the prevention of ischemic stroke by statin treatment.In elderly patients without clinically recognized atherosclerotic CVD, the risk of cardiovascular mortality was significantly reduced with statin treatment than with non-users. In participants with type 2 diabetes, statin treatment was associated with a reduction in ischemic stroke.

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the “severe beta-cell dysfunction” group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The “severe insulin resistance” group had higher odds of carotid artery plaque presence (aOR 1.238). The “severe insulin resistance and beta-cell dysfunction” group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p

Background: Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely asso ciated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the as sociation between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function. Methods: This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated. Results: Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL, P=0.005). A higher baseline level of A-FABP was associated with a greater risk of developing rapid renal function decline, in dependent of age, sex, duration of diabetes, body mass index, systolic blood pressure, history of cardiovascular disease, baseline eGFR, urine albumin creatinine ratio, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein and use of thiazolidinedione, insulin, angiotensin-converting-enzyme inhibitors and angiotensin II-receptor blockers and statin (odds ra tio, 3.10; 95% confidence interval, 1.53 to 6.29; P=0.002). Conclusion: A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.

Background: Changes in muscle mass and strength can be caused by multiple endocrine factors, including thyroid dysfunction. However, the relationship between thyroid function and muscle strength in...

This study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.The study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment.The baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (Dapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Background and aims Sarcopenia leads to metabolic and vascular abnormalities. However, little is known regarding the independent relationship between skeletal muscle mass and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between skeletal muscle mass and carotid atherosclerosis in men and women with T2DM. Methods In this cross-sectional study, a total of 8202 patients with T2DM were recruited from the Seoul Metabolic Syndrome cohort. Skeletal muscle mass was estimated using bioimpedance analysis, while skeletal muscle mass index (SMI, %) was defined as total skeletal muscle mass (kg)/body weight (kg) × 100. Both carotid arteries were examined by B-mode ultrasound. Carotid atherosclerosis was defined by having a carotid plaque or mean carotid intima-media thickness (IMT) ≥1.1 mm. Results Among the entire population, 4299 (52.4%) subjects had carotid atherosclerosis. The prevalence of carotid atherosclerosis increased with decreasing SMI quartiles for both sexes. The odds ratios for carotid atherosclerosis were 2.33 (95% confidence interval [CI], 1.17–4.63) and 2.24 (95% CI, 1.06–4.741) in the lowest versus highest SMI quartile in men and women, respectively, after the adjustment for clinical risk factors. In men, the risk of atherosclerosis increased linearly with decreasing SMI quartiles (p for trend = 0.036). Conclusions Low skeletal muscle mass was independently associated with the presence of carotid atherosclerosis in men and women with T2DM.

Background: Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia.Methods: Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay.Results: The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P

Despite the close relationship between osteoporosis and chronic pulmonary diseases, few studies have evaluated relationships between pulmonary functions and bone quality. We investigated associations between pulmonary function test results and femoral neck strength indices (SIs) in Korean men.This population-based, cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey IV on 936 men aged ≥ 19 years. Pulmonary functions (forced vital capacity [FVC] and forced expiratory volume in one second [FEVThe 443 (47.3%) of the 936 men were current smokers. FVC, FVC percentage with respect to the expected normal value, FEVReduced pulmonary function was correlated with reduced femoral neck strength, even after adjusting for smoking history in Korean men. Femoral neck SIs might be useful tools for evaluating bone health in men with reduced pulmonary function.

The causal relationship between low muscle mass and development of chronic kidney disease (CKD) is uncertain in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between low muscle mass or sarcopenic obesity and the risk of incident CKD in patients with T2DM. A total of 3,123 patients with T2DM with preserved renal function were followed up for incident CKD. Skeletal muscle mass was estimated from bioelectrical impedance analysis. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2. Sarcopenic obesity was defined as the coexistence of sarcopenia and abdominal obesity. During 8.9 years of follow-up, 530 (17.0%) patients developed incident CKD. When subjects were divided into three groups based on sex-specific tertiles, lower muscle mass was not associated with an increased risk of incident CKD after adjustment for risk factors. However, when patients were divided into four groups according to the presence of sarcopenia and obesity, sarcopenic obesity was associated with an increased risk of incident CKD (adjusted hazard ratio 1.77; 95% confidence interval 1.24-2.51; p=0.001) compared to the other groups. Sarcopenic obesity, but not low muscle mass alone, may increase the risk of CKD in patients with T2DM.

Objective The onset and progression of sarcopenia are highly variable between individuals due to genetic and environmental factors. However, studies that have measured muscle strength directly in large numbers of matched parent-adult offspring pairs are limited. In this study, we investigated familial correlation and heritability of handgrip strength (HGS) in Korean adults. Methods This was a family-based cohort study from the Korea National Health and Nutrition Examination Survey (2014-2019) including 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations for HGS were calculated in different types of relative pairs. Variance component methods were used to obtain heritability estimates. Results Mean HGS of parents were 39.3 ± 7.5 kg in fathers and 24.4 ± 5. 0 kg in mothers and those of offspring were 41.8 ± 8. 0 kg in sons and 24. 0 ± 4.8 kg in daughters. Correlation coefficient estimates between parent-offspring pairs, sibling pairs, and spouse pairs for HGS were significant as 0. 07, 0.10, and 0.23 (p Conclusion Muscle strength showed a familial correlation in Korean adults. A significant heritable tendency of muscle strength from parents to their adult offspring and common shared environmental influence can explain this correlation. Presentation: No date and time listed

Introduction Studies have been conducted to assess the association between the use of statin and risk of new onset osteoporosis or osteoporotic fractures, however, they have shown conflicting results. We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in elderly population. Methods In this population cohort study with Korean National Health Insurance Service-Senior Cohort database, a total of 365,656 elderly (≥60 years) without previous history of osteoporosis were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to December 2012. Incidences of major osteoporotic fractures and site specific fractures were compared using the Cox proportional hazards model with use the inverse probability weighting method. Results During years follow-up period, 54,959 major osteoporotic fractures occurred; the risk of major osteoporotic fractures was significantly reduced (OR,0.769; 95% CI,0.716-0.826) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for both vertebral fracture (OR,0.701; 95% CI,0.641-0.767) and non-vertebral fracture (OR,0.807; 95% CI,0.726-0.898). Longer duration and higher cumulative dose of statin, defined by cumulative daily defined dose, were negatively associated with the risk of major osteoporotic fracture. Conclusion In this population-based cohort study, the use of statin was associated with significant reduction in the risk of osteoporotic fractures in elderly patients without previous history of osteoporosis. Presentation: No date and time listed

Objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and the development of CKD is uncertain, particularly in patients with type 2 diabetes. We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with type 2 diabetes. Research Design and Methods: In this longitudinal cohort study of patients with type 2 diabetes, 3,188 patients with preserved renal function were followed for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography without any other causes of chronic liver diseases. Advanced liver fibrosis of NAFLD was defined as NAFLD fibrosis score >0.675. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Results: At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3 ± 3.6 years, 472 (14.8%) patients developed incident CKD, 220 (15.1%) in the non-NAFLD group, 226 (12.8%) in the hepatic steatosis alone group and 26 (27.7%) in the advanced liver fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared with the non-NAFLD group (p = 0.79). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio [HR] 1.78 (95% confidence interval [CI] 1.14-2.76), p=0.011). Conclusions: Advanced liver fibrosis in NAFLD is independently associated with an increased risk of incident CKD in patients with type 2 diabetes. Disclosure D. Seo: None. Y. Cho: None. S. Ahn: None. S. Seo: None. S. Hong: None. Y. Lee: None. S. Kim: None. Funding National Research Foiundation (2017R1D-1A1B03034581)

Background Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. Methods This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. Results The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40–1.28) in the SERMs group compared to BP group. Older age (60–69 vs. 50–59 years: HR, 3.77; 95% CI, 2.07–6.86 and 70–79 vs. 50–59 years: HR, 5.88; 95% CI, 3.14–11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35–8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01–5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02–4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29–14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05–7.0) increased VTE risk. Conclusion SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk., Graphical Abstract

We aimed to investigate the association between a new definition of metabolic health (MH) and subclinical atherosclerosis in a cohort of patients without previous cardiovascular disease (CVD). In total, 7824 community-dwelling adults were categorized as normal weight, overweight, or obese. Metabolically healthy obesity (MHO) was defined as obesity accompanied by all of the following criteria: systolic blood pressure (BP) < 130 mmHg, no use of BP-lowering medication, waist-hip ratio

Background The socioeconomic burdens of osteoporosis and related fractures have increased in parallel with population aging. The Korea Society of Bone and Mineral Research published fact sheets on these topics in 2017, 2018, and 2019. This study provides complied epidemiological data based on these fact sheets for understanding current status of osteoporosis in Korea. Methods Data from the Korea National Health and Nutrition Examination Survey (2008-2011) performed by the Korea Centers for Disease Control and Prevention and from National Health Information database (2008-2016) by National Health Insurance Service of Korea was used for analyzing the prevalence and incidence of osteoporosis and related fractures, respectively, fatality rates after fractures, and prescription status of anti-osteoporotic medications (AOMs). Results Among Korean adults aged ≥50 years, 22.4% and 47.9% had osteopenia or osteoporosis, respectively. Incidences of osteoporotic hip, vertebral, humerus, and distal radius fractures plateaued in 2013. The cumulative incidence of subsequent fractures gradually increased over 4 years of follow-up once an osteoporotic fracture occurred. Crude fatality rates in the first 12 months after hip fracture were 14.0% for women and 21.0% for men. Only 33.5% of patients with osteoporosis took AOMs, and even after an osteoporotic fracture, only 41.9% of patients took AOMs within the following 12 months. Despite a steady increase in AOM prescriptions of ~6% per annum, only 33.2% of patients were medication compliant (medication possession ratio ≥80%) at 12 months after treatment initiation. Conclusions Continuous efforts are required to diagnose patients at high risk of fracture and ensure proper management in Korea.

Background: Recent studies investigated the association between nonalcoholic fatty liver disease (NAFLD) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) but the results are inconclusive. Here we aimed to investigate the effect of obesity on the association between NAFLD and DKD in a large cohort of participants with T2DM. Methods: In this cross-sectional study, a total of 3,439 patients (1,710 men and 1,729 women) with T2DM were recruited from the Seoul Metabolic Syndrome cohort between 2003 and 2016. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver diseases. Advanced fibrosis was defined as FIB4 index ≥ 1.45. DKD was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Results: The mean age was 57.4 ± 10.3 years and duration of diabetes was 7.7 ± 7.1 years. Two hundred and fifty subjects (7.3%) had DKD and 1869 (54.3%) subjects had NAFLD. The prevalence of DKD were 7.0%, 4.5% and 11.9% in no-NAFLD group, liver steatosis only group and advanced fibrosis group respectively (p Conclusion: This study suggests that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of DKD in non-obese patients with T2DM. Disclosure D. Seo: None. Y. Cho: None. S. Ahn: None. S. Hong: None. Y. Lee: None. Y. Choi: None. B. Huh: None. K. Huh: None. S. Kim: None.

Malignant pheochromocytoma and paraganglioma can be defined only after the development of metastases in nonchromaffin tissues. There is no single clinical parameter that is sufficiently reliable to predict metastatic potential, so our goal was to develop a prediction model based on multiple clinical parameters.The baseline age, size, extra-adrenal location, secretory type score was calculated in a retrospective cohort study comprising 333 patients with pheochromocytoma and paraganglioma. In each patient, each variable for age ≤35 years, tumor size ≥ 6.0 cm, extra-adrenal, and norepinephrine-secretory type was coded as 1 point (otherwise 0 point); these points were summed to yield age, size, extra-adrenal location, secretory type score.Metastases occurred in 23 of 333 patients (6.9%). Metastatic pheochromocytoma and paraganglioma was associated with age ≤35 years (hazard ratio [HR] 2.74, 95% confidence interval [95% CI] 1.19-6.35), tumor size ≥6.0 cm (HR 2.43, 95% CI 1.06-5.56), extra-adrenal location (HR 2.73, 95% confidence interval 1.10-7.40), and tumor producing only norepinephrine (HR 2.96, 95% CI 1.30-6.76). The area under the curve of the age, size, extra-adrenal location, secretory type score was 0.735. There was a significant difference in metastasis-free survival between participants with age, size, extra-adrenal location, secretory type score ≥2 and score2 (P.0001 by the log rank test). The negative predictive value of this system was 96.5% for a cutoff point of 2.We developed a new prediction model, the age, size, extra-adrenal location, secretory type score, based on multiple clinical parameters to assess the metastatic potential of pheochromocytoma and paraganglioma.

Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH. One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing’s syndrome (CS), and nonfunctional AI (NFAI). We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women). After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (β = −0.133, P = 0.045) and women (β = − 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (β = − 0.252, P

Analyses using a nationally representative cohort have revealed that high fatty liver index (FLI) is associated with low bone mineral density (BMD) regardless of insulin resistance in men, thereby supporting the deteriorated bone metabolism in nonalcoholic fatty liver disease (NAFLD). NAFLD is linked to deteriorated bone health. We investigated the association of FLI, a scoring model for NAFLD, with BMD. This was a population-based, cross-sectional study from the Korea National Health and Nutrition Examination Surveys including 4264 Koreans (1908 men and 2356 women). FLI was calculated using body mass index, waist circumference, serum triglyceride, and gamma-glutamyltranspeptidase level. Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. BMD was measured using dual-energy X-ray absorptiometry at the lumbar spine, total hip, femoral neck, and whole body. Men had a higher FLI than women, while the HOMA-IR index was similar between men and women. The significant association between FLI and BMD was observed only in men, but not in women. FLI was negatively correlated with total hip, femoral neck, and whole body BMD in men after adjusting for all potential confounders, including HOMA-IR (P

As populations continue to age worldwide, sarcopenic obesity has heightened interest due to its medical importance. Although much evidence now indicates that n-3 fatty acids (FAs) may have beneficial effects on body composition including fat and muscle, their exact mechanisms have not yet been elucidated. Because free FA receptor 4 (FFA4) has been reported to be a receptor for n-3 FAs, we hypothesized that the protective role of n-3 FAs on body composition could be mediated by FFA4. To test this possibility, we generated mice overexpressing n-3 FAs but lacking FFA4 by crossing fat-1 transgenic (fat-1 Tg+) and FFA4 knockout (Ffar4 -/-) mice. Because fat-1 Tg+ mice, in which n-6 is endogenously converted into n-3 FAs, contain high n-3 FA levels, they could be a good animal model for studying the effects of n-3 FAs in vivo. Male and female littermates were included in high-fat-diet- (HFD) and ovariectomy-induced models, respectively. In the HFD model, male fat-1 Tg+ mice had a lower percentage of fat mass and a higher percentage of lean mass than their wild-type littermates only when they had the Ffar4 +/+ not the Ffar4 -/- background. Female fat-1 Tg+ mice showed less increase of fat mass percentage and less decrease of lean mass percentage after ovariectomy than wild-type littermates. However, these effects on body composition were attenuated in the Ffar4 -/- background. Taken together, our results indicate that the beneficial effects of n-3 FAs on body composition were mediated by FFA4 and thus suggest that FFA4 may be a potential therapeutic target for modulating sarcopenic obesity.

Current evidences continue to support the clinical application of bone turnover markers (BTMs) in the management of postmenopausal osteoporosis. The limitations of bone mineral density measured by dual energy X-ray absorptiomet especially emphasize the beneficial roles of BTMs, such as serum C-terminal telopeptide of type I collagen and serum procollagen type I N-propeptide, as monitoring tools to assess the responses to treatment. Therefore, the proper application and assessment of BTM in clinical practice is very important. However, their use in Korea is still insufficient. Therefore, the BTM committee has set up by the Korean Society for Bone and Mineral Research have been constituted and provided a position statement which will suggest on the clinical application of BTM for the management of postmenopausal osteoporosis in Korea.

Background: Sarcopenia, an age-related decline in skeletal muscle mass, leads to metabolic and vascular abnormalities. However, little is known regarding the independent relationship between skeletal muscle mass and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to evaluate the association of skeletal muscle mass with markers of carotid atherosclerosis, carotid intima-media thickness (CIMT) and carotid artery plaque, in men and women with T2DM. Methods: In this cross-sectional study, a total of 8,918 patients (4,520 men and 4,398 women) with T2DM were recruited from the outpatient clinic of Huh’s Diabetes Center from 2003 to 2016. Skeletal muscle mass was estimated from bioimpedance analysis measurements and skeletal muscle mass index (SMI, %) was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. Carotid ultrasonography was performed to measure mean CIMT of both common carotid arteries. Carotid artery plaque was defined as a focal structure protruding into the lumen of the vessel of ≥50% than the surrounding area. Results: In both men and women, the presence of carotid artery plaque was higher with decreasing SMI quartiles. In men, this association remained significant after adjustment for additional risk factors (ptrend Conclusion: Low muscle mass is associated with the presence of carotid artery plaque in men with T2DM. Disclosure M. Nam: None. D. Seo: None. M. Jung: None. S. Ahn: None. S. Hong: None. Y. Lee: None. Y. Choi: None. B. Huh: None. K. Huh: None. S. Kim: None. Funding National Research Foundation of Korea (2017R1D-1A1B03034581)

Although both liver and muscle are metabolically active endocrine organs, and non-alcoholic fatty liver disease (NAFLD) and sarcopenia may share common pathogenic determinants, there have been few clinical studies of the relationship between NAFLD and muscle strength, especially in the elderly. We conducted a nationally representative population-based, cross-sectional study using data from the Korea National Health and Nutrition Examination Survey, which involved 1,897 men aged ≥50 years and 2,206 postmenopausal women. NAFLD was defined using the hepatic steatosis index (HSI) and low muscle strength was defined using the Korea-specific cut-off point of hand grip strength (HGS). Men and women with NAFLD had 7.3% and 7.9% lower HGS than controls, respectively. The odds ratios for low muscle strength in the presence of NAFLD were 2.51 in men and 2.34 in women. HSI inversely correlated with HGS in both men and women. Consistently, compared with men and women in the lowest HSI quartile, those in the highest quartile had 7.6% and 12.4% lower HGS, respectively, and were 5.63- and 3.58-times more likely to have low muscle strength, respectively. These results provide the first clinical evidence that NAFLD can be associated with muscular impairment in older adults, as demonstrated by lower muscle strength.

The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state-which is a risk factor for cardiovascular disease (CVD)-remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20-10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15-135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.

SummaryObjective There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic–pituitary–adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications. Design Prospective and cross-sectional, observational, multicentre study in Korea. Methods After exclusion of overt Cushing's syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test. Results Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone–sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98–566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84–6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality. Conclusions Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians.

Heredity is an important risk factor for osteoporotic fracture, but it remains unclear whether genetic factors improve the predictability of future fracture occurrence.To compare an integration model of genetic profiling with the current model for predicting future fracture occurrence.A retrospective observational cohort study.Postmenopausal women aged 45-93 years who were untreated (n = 117), hormone-treated (n = 491), or bisphosphonate (BP)-treated (n = 415), with a mean 6.1-year follow-up.The main outcome was incident fractures. Ninety-five single nucleotide polymorphisms were genotyped. We calculated the Korean-specific genetic risk score 35 (GRS35) from 35 single nucleotide polymorphisms associated with osteoporosis-related traits at the baseline visit.Osteoporotic fracture occurred more frequently in the highest GRS35 tertile group than in the lower two tertile groups after adjustments for confounders (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.17-2.55). The associations of the GRS35 with incident fracture were only significant in the BP group (HR, 2.25; 95% CI, 1.28-3.95) and not in the untreated (HR, 1.26; 95% CI, 0.34-4.66) and hormone-treated (HR, 1.21; 95% CI, 0.62-2.36) groups. Integration of the GRS35 into the current model further improved its predictability for incident fracture occurrence by 6.3% (P = .010).Genetic profiling can more accurately predict future fracture risk, especially in individuals taking BPs.

Background: Rapid renal function decline has been recognized as an important predictor for diabetic nephropathy (DN). Adipocyte fatty acid-binding protein (A-FABP) is a major cytoplasmic protein in adipocytes and is closely associated with metabolic syndrome and type 2 diabetes. We aim to investigate the role of adipokines including A-FABP and inflammatory cytokines in the development of rapid renal function decline in type 2 diabetes and normal renal function. Methods: A total of 456 subjects with type 2 diabetes with normal renal function were recruited from an outpatient clinic at the Diabetes Center of Inha University Hospital and were followed up for 6 years with serial glomerular filtration rate (GFR) measurements. The serum levels of tumor necrosis factor (TNF)-a, and interleukin (IL)-6, high molecular weight (HMW) adiponectin, endogenous secretory receptor for advanced glycation end products (esRAGE), A-FABP and pentraxin-related protein (PTX3) were measured at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year. Results: During follow-up, 120 participants (26.3%) developed rapid renal function decline and mean annual eGFR decline was -5.4 ± 2.7% and -0.6 ± 2.4% in decliners and non-decliners, respectively. Median A-FABP levels were significantly higher in patients with rapid decliners than in non-decliners (19.1 vs. 16.8 ng/ml, p=0.011). No significant difference of three cytokines levels were observed between groups. Each log unit increase of A-FABP was independently associated with greater risk of rapid renal function decline (odds ratio [OR] = 3.60; 95% confidence interval [CI] 1.95-6.66; p < 0.001) after adjustments for sex, BMI, A1C, GFR, hypertension, presence of carotid artery plaque and urine albumin creatinine ratio. Conclusions: High plasma A-FABP was an independent risk factor for rapid renal function decline in type 2 diabetes and normal renal function. Disclosure D. Seo: None. S. Kim: None. S. Ahn: None. S. Hong: None. M. Nam: None.

Background: Recent clinical evidences indicate that early rapid renal function decline is closely associated with the development of diabetic kidney disease. We have investigated the incidence and baseline clinical predictors of rapid renal function decline in patients with type 2 diabetes and normal baseline renal function. Methods: A total of 967 type 2 diabetic patients from the Korean National Diabetes Program (KNDP), a prospective, multicenter, observational cohort study, with serial GFR measurement for 5 years and normal renal function were included for the analysis. Rapid renal function decline was defined as an eGFR decline >3.3% per year. Carotid ultrasonography was used to assess carotid intima-media thickness (IMT) and the presence of plaque. Results: The mean age was 53.7 years with body mass index of 25.4 kg/m2. Rapid renal function decline developed in 158 participants (16.3%) and average GFR decline was -5.2 ± 1.9% /year in rapid decliners and -0.4 ± 1.9% /year in non-decliners. There were no differences in the presence of albuminuria or retinopathy between the rapid decliners and non-decliners at baseline. Multivariable logistic regression analyses revealed that female sex (odds ratio (OR) 4.80 [95% CI 2.69-8.56], p Conclusions: Our study suggests the need for close monitoring of renal function and early intensive management in patients with type 2 diabetes and carotid atherosclerosis. Disclosure D. Seo: None. S. Kim: None. S. Ahn: None. S. Hong: None. M. Nam: None. J. Woo: None. S. Baik: None. K. Lee: None. Y. Kim: None. Y. Park: None.

The effects of catecholamine excess due to pheochromocytoma on body composition, including skeletal muscle mass, are unknown. Here, we investigated the effects of catecholamine metabolites on body composition in subjects with pheochromocytoma. After body compositions using bioelectrical impedance analysis, urinary metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two groups. After adjustments for confounders, UM (β = − 0.171, P = 0.006) and UNM (β = − 0.249, P

Despite the well-known deleterious effects of cortisol on skeletal muscle, whether subtle cortisol excess in subclinical hypercortisolism (SH) affects skeletal muscle mass is unknown. Our objective was to understand the effects of the cortisol level on skeletal muscle mass in patients with SH. We compared skeletal muscle mass and fat mass (FM) between 21 patients with SH (12 women and 9 men) and 224 controls (67 women and 157 men) with nonfunctioning adrenal incidentaloma (NFAI). Medical records were reviewed, and we measured body composition parameters using bioelectrical impedance analysis and serum cortisol levels after the overnight 1-mg dexamethasone suppression test (DST). After adjusting for confounding factors, 1-mg DST levels were inversely correlated with appendicular skeletal muscle mass (ASM) (γ = −0.245, P = 0.040), lower limb ASM (γ = −0.244, P = 0.040), and appendicular skeletal muscle index (ASMI; height-adjusted ASM) (γ = −0.229, P = 0.048) in all women, but not men. ASM and ASMI were significantly lower by 6.2% (P = 0.033) and 5.9% (P = 0.046), respectively, in women with SH compared with those with NFAI, but not men. Conversely, FM and percent fat mass were similar between the two groups. Compared with women with NFAI, among those with SH, lower limb, but not upper limb, ASM was lower by 6.8% (P = 0.020). This study showed that women with SH had lower skeletal muscle mass, especially of the lower limb, and suggested that subtle cortisol excess also has adverse effects on skeletal muscle metabolism.

SummaryObjective Fracture risk in type 2 diabetes mellitus with insulin resistance is increased, despite relatively preserved bone mineral density (BMD). In this present study, we investigated the relationship between insulin resistance and composite indices of femoral neck strength in Koreans. DesignA population-based, cross-sectional study from the Korea National Health and Nutrition Examination Survey Participants 1,243 men and 1,433 women. Measurements Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. Femoral neck width and axis length were measured from hip dual-energy X-ray absorptiometry scans and combined with BMD, weight, and height to calculate composite indices of femoral neck strength relative to load: compression (CSI), bending (BSI) and impact strength indices (ISI). Results HOMA-IR showed an inverse relationship with CSI, BSI and ISI in both genders before and after adjusting for confounders (P < 0.001–0.029). CSI was more strongly associated with HOMA-IR than BSI and/or ISI in both genders (P < 0.001–0.013). When men were stratified according to HOMA-IR quartiles, all strength indices decreased as the quartile increased, after adjusting for all potential confounders (P for trend < 0.001–0.001), whereas CSI and ISI did in women (P for trend = 0.012 and 0.002, respectively). Fasting insulin levels, but not glucose levels, were negatively associated with all strength indices regardless of confounders (P < 0.001–0.044). Conclusions Insulin resistance is associated with low femoral neck strength, particularly against the compressive load. These findings suggest that improved approaches to evaluate bone health are needed in insulin-resistant individuals. This article is protected by copyright. All rights reserved.

Pro-inflammatory cytokines play important roles in bone metabolism and several studies have shown that carcinoembryonic antigen (CEA) may promote inflammation. We investigated the association of serum CEA levels with the risk of osteoporosis and incident fracture.We performed a small cross-sectional study with 302 Korean women and a large, longitudinal study with 7192 Korean women in an average 3-year follow-up period. For the cross-sectional study, bone mineral density (BMD) and bone turnover markers (BTMs) were measured. For the longitudinal study, incident fractures in the follow-up period were identified by using the selected International Classification of Diseases, 10th revision (ICD-10) codes and the nationwide claims database of the Health Insurance Review and Assessment Service of Korea.In the cross-sectional study, serum CEA levels correlated negatively with BMD at the lumbar spine (γ=-0.023; P=0.029) and positively with BTMs (γ=0.122 to 0.138, P=0.002 to P0.001) after adjustment for confounding variables. In the longitudinal study, 254 (3.5%) women developed incident fractures in the follow-up period (2.8±1.3 years). After adjustment for potential confounders, the hazard ratio (HR) per 1 ng/mL increment of the baseline CEA level for the development of incident fracture was 1.22 [95% confidence interval (CI): 1.05-1.42]. The HR was markedly higher in subjects in the highest CEA quartile category compared with those in the lowest CEA quartile category (HR=1.54, 95% CI: 1.04-2.28).Therefore, serum CEA may be a biomarker of the risk of incident fracture in postmenopausal Korean women.

Despite experimental and animal evidence showing the detrimental effects of platelet-activating factor (PAF) on bone metabolism, there are no clinical studies relating PAF to osteoporosis-related phenotypes. This case-control study investigates the association between plasma PAF, osteoporotic vertebral fracture (VF), and bone mineral density (BMD) in postmenopausal Korean women. Among 474 eligible women not taking any drug or having any disease that could affect bone metabolism, we identified 73 cases defined as subjects with radiological VF. The controls were randomly selected from the remaining 401 subjects and matched 1:1 to cases in terms of both age and body mass index (BMI). Lateral thoracolumbar radiographs, BMD, and plasma PAF levels were determined for all subjects. Postmenopausal women with VF demonstrated 34.6 % higher plasma PAF levels than subjects without VF after adjusting for age, BMI, smoking habits, alcohol intake, regular exercise, and parental history of osteoporotic fractures (P = 0.021). Multiple logistic regression analyses revealed that the odds ratio for VF linearly increased across increasing PAF quartiles (P for trend = 0.040) and the odds for VF were 2.88-fold higher in subjects in the highest quartile in comparison with those in the lowest quartile (95 % CI 1.04-8.01). Plasma PAF levels were inversely correlated with BMD at various sites (γ = -0.253 to -0.176, P = 0.003-0.041). These findings suggest that plasma PAF may be a potential biomarker for predicting poor bone health in postmenopausal women.

Context Despite the potential detrimental effects of aldosterone excess on bone metabolism, discrepancies exist between fracture risk and bone mass in patients with and without primary aldosteronism (PA). Objective To clarify the possibility that aldosterone excess might mainly affect bone properties not explained by the bone mineral density (BMD). Design, Setting, and Patients Among 625 consecutive patients with newly diagnosed adrenal incidentaloma (AI), 72 with biochemically confirmed PA and 335 with nonfunctional AI were defined as cases and controls, respectively. Results In women, although no statistically significant differences in lumbar spine BMD were found between groups, the lumbar spine trabecular bone score (TBS) was significantly lower in patients with PA than in controls after adjustment for confounders (P = 0.007). Consistently, the plasma aldosterone concentration (PAC) correlated inversely with the lumbar spine TBS (P = 0.028) but not with bone mass in women. Compared with women in the lowest PAC quartile, those in the highest PAC quartile had significantly lower lumbar spine TBSs (P = 0.004). Importantly, all these observations in women remained statistically significant after additional adjustment for the lumbar spine BMD in the multivariable model. However, BMD and TBS at the lumbar spine did not differ according to the presence of PA and the level of PAC in men. Conclusion These findings provide clinical evidence that aldosterone excess in PA might contribute to deteriorated bone quality through weak microarchitecture, regardless of bone mass, especially in women.

Context Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. Objective To clarify the link between the sympathetic nervous system and the skeleton in humans. Design, setting, and patients Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. Results After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. Conclusions This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.

Oxidative stress has detrimental effects on bone metabolism, and gamma-glutamyl transferase (GGT) is known to play an important role in the generation of free radical species through the extra-cellular hydrolysis of glutathione, the main cellular antioxidant. We performed a large longitudinal study with an average follow-up period of 3 years to investigate the association between baseline serum GGT levels and the development of future osteoporotic fractures (OFs) in men. A total of 16,036 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea using selected ICD-10 codes. Among the study subjects, 156 cases (1.0%) developed incident OFs during the study period. The event rate was 32.7 (95% CI = 28.0-38.3) per 10,000 person-years. Multivariable adjusted Cox proportional hazard analyses adjusted for age, body mass index, lifestyle factors, and medical and drug histories revealed that the hazard ratio per standard deviation increase of the baseline GGT levels for the development of incident fractures was 1.115 (95% CI = 1.011-1.230). These data provide the first epidemiological evidence, in support of previous in vitro and animal studies, of the harmful effects of GGT on bone metabolism, and indicate that the serum GGT level may be a useful biomarker of poor bone health outcomes in men.

Background Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function. Methods In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year. Results Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P

Background There has been interest in the clinical potential of bone turnover markers (BTMs) as tools both for assessing fracture risk and for monitoring treatment. However, the practical use of BTMs has been limited by their biological variability and difficulties in the interpretation of results. We investigated the current situation of application of BTMs by clinicians in Korea for the management of osteoporosis through a survey asking the patterns of BTMs prescription in clinical practice. Methods The survey was conducted online using the “google survey” by the BTM committee authorized by the Korean Society for Bone and Mineral Research. Results Total 108 clinicians responded the survey. Most of the respondents prescribed BTMs (80.6%) when they prescribed anti-osteoporotic medications (AOMs). The most frequently prescribed bone resorption and formation markers were serum C-terminal telopeptide of type I collagen (90.7%) and osteocalcin (65.1%), respectively. BTMs were mostly prescribed before starting AOMs (90.8%) and used for the purpose of evaluating treatment response (74.4%). Treatment response and compliance to AOMs were evaluated according to the change of absolute value of BTMs (55.1%). The respondents complained difficulties in the interpretation of BTMs (33.3%), the choice of proper BTMs (17.2%), and the proper sample preparation and handling (13.8%). Conclusions In Korea, most of clinicians recognized the benefit of BTMs in the management of osteoporosis. However, there are limitations in the broad use of these markers in clinical practice. Therefore, a clear recommendation for BTM in Korea enhances their use in clinical practice.

Clinical risk factors (CRFs), with or without bone mineral density (BMD), are used to determine the risk of osteoporotic fracture (OF), which has a heritable component. In this study we investigated whether genetic profiling can additionally improve the ability to predict OF. Using 1229 unrelated Korean postmenopausal women, 39 single-nucleotide polymorphisms (SNPs) in 30 human genomic loci were tested for association with osteoporosis-related traits, such as BMD, osteoporosis, vertebral fracture (VF), nonvertebral fracture (NVF), and any fracture. To estimate the effects of genetic profiling, the genetic risk score (GRS) was calculated using five prediction models: (Model I) GRSs only; (Model II) BMD only; (Model III) CRFs only; (Model IV) CRFs and BMD; and (Model V) CRFs, BMD, and GRS. A total of 21 SNPs within 19 genes associated with one or more osteoporosis-related traits and were included for GRS calculation. GRS associated with BMD before and after adjustment for CRFs (p ranging from

Bilirubin is known to have a physiologic role as an antioxidant that efficiently scavenges peroxyl radicals and suppresses oxidation, and oxidative stress has detrimental effects on bone metabolism. In the present study, we performed a 3-year longitudinal study of healthy middle-aged men, investigating the association between serum total bilirubin concentrations and annualized changes in bone mineral density (BMD). The study enrolled a total of 917 Korean men aged 40 years or older who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The overall mean annualized rates of bone loss at the total femur, femoral neck, and trochanter were -0.25 %/year, -0.34 %/year, and -0.44 %/year, respectively. After adjustment for potential confounders, the rates of bone loss at all proximal femur sites were significantly attenuated in a dose-response fashion across increasing bilirubin concentrations (P = 0.006-0.046). Moreover, compared to subjects in the lowest bilirubin quartile category, those in the highest bilirubin quartile category showed significantly less bone loss at all proximal femur sites after adjustment for confounding factors (P = 0.010-0.048). This study provides the first clinical evidence that serum total bilirubin could be a protective marker against future bone loss, especially in subjects without liver diseases.

Introduction Despite extensive evidence demonstrating the direct, detrimental role of homocysteine on bone metabolism, the effects of serum total homocysteine (tHcy) on bone loss are still equivocal. In the present study, we performed a longitudinal study on healthy participants of various ages of both sexes in order to investigate the association between serum tHcy concentrations and annualized changes in bone mineral density (BMD). Methods A total of 460 Koreans ≥ 30 years of age received comprehensive, routine health examinations for an average period of 3 years. The BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. Results After adjusting for potential confounders, the rates of bone loss at the proximal femur sites were significantly accelerated in a dose–response fashion across increasing tHcy concentrations in premenopausal women and men, but not in postmenopausal women. Consistently, compared with subjects in the lowest tHcy quartile, premenopausal women in the third and/or highest tHcy quartile and men in the highest tHcy quartile showed significantly higher rates of bone loss at all proximal femur sites ( p = 0.015–0.048) and at the total femur and femur neck ( p = 0.008–0.013), respectively. In contrast, there were no differences in terms of bone loss among the tHcy quartiles for postmenopausal women. Conclusion These data provide the first clinical evidence that increased tHcy levels could be an independent risk factor for the future deterioration of bone mass in premenopausal women and men.

Postmenopausal women with osteoporotic fracture (OF) had higher plasma dipeptidyl-peptidase 4 (DPP4) levels than those without. Furthermore, higher plasma DPP4 levels were significantly associated with higher bone turnover and a higher prevalence of OF. These results indicated that DPP4 may be associated with OF by mediating bone turnover rate. Evidence indicates that dipeptidyl-peptidase 4 (DPP4) plays a distinct role in bone metabolism. However, there has been no report on the association, if any, between circulating DPP4 levels and osteoporosis-related phenotypes, including osteoporotic fracture (OF). Therefore, we performed a case-control study to investigate these associations in postmenopausal women. This study was conducted in multiple centers in Korea. We enrolled 178 cases with OF and 178 age- and body mass index-matched controls. OF was assessed by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs. Bone turnover markers (BTMs), bone mineral density (BMD), and plasma DPP4 levels were obtained in all subjects. After adjustment for potential confounders, subjects with OF had significantly higher DPP4 levels than those without (P = 0.021). Higher DPP4 levels were significantly positively associated with higher levels of all BTMs, but not with BMD at all measured sites. The differences in DPP4 levels according to OF status disappeared after an additional adjustment for each BTM, but not after adjustment for any BMD values. BTMs explained approximately half of the relationship between DPP4 and OF. The risk of OF was 3.80-fold (95% confidence interval = 1.53–9.42) higher in subjects in the highest DPP4 quartile than in those in the lowest quartile after adjustment for potential confounders, including femoral neck BMD. DPP4 may be associated with OF by at least partly mediating the bone turnover rate. Circulating DPP4 levels may be a potential biomarker that could increase the predictive power of current fracture risk assessment models.

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4(-/-)) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1(Tg+)) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4(-/-) and fat-1(Tg+) mice over two generations to generate four genotypes of mice littermates: Ffar4(+/+);fat-1(Tg-), Ffar4(+/+);fat-1(Tg+), Ffar4(-/-);fat-1(Tg-), and Ffar4(-/-);fat-1(Tg+). Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1(Tg+) mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In a high-fat diet-fed model, male fat-1(Tg+) mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.