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Background: Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.Methods: We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.Results: As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).Conclusion: Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

Background: Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.Methods: We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).Results: After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index

Background: Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.Methods: We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.Results: A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.Conclusion: The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

Background: Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.Methods: We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.Results: On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).Conclusion: Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

Background Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression. Methods We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017. Results Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72). Conclusion Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.

OBJECTIVE To investigate the effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a 12-week, open-label, randomized controlled trial. A total of 126 participants were 1:1 randomized to either the intervention group (structured education + isCGM) or the control group (standard care with blood glucose monitoring). The Self-Evaluation Of Unhealthy foods by Looking at postprandial glucose (SEOUL) algorithm was developed and applied to aid structured education in guiding patients to follow healthy eating behavior depending on the postprandial glycemic response. The primary end point was the change in HbA1c level from baseline. RESULTS Implementation of the SEOUL algorithm with isCGM was associated with greater improvement in HbA1c than with standard care (risk-adjusted difference −0.50%, 95% CI −0.74 to −0.26, P < 0.001). Participants in the intervention group had a greater reduction in fasting blood glucose and body weight (−16.5 mg/dL, 95% CI −30.0 to −3.0, P = 0.017; −1.5 kg, 95% CI −2.7 to −0.3, P = 0.013, respectively). The score sum for the Korean version of the revised Summary of Diabetes Self-Care Activities Questionnaire increased in both groups but to a greater extent in the intervention group (mean difference 4.8, 95% CI 1.7–8.0, P = 0.003). No severe hyperglycemia or hypoglycemia was reported in either group of patients. CONCLUSIONS Patient-driven lifestyle modification primarily focused on eating behavior using isCGM effectively lowered HbA1c levels in patients with T2D.

Aims Heart failure (HF) is associated with obesity, but the relationship between weight change and HF is inconsistent. We examined the relationship between weight change and the incidence of HF in the Korean population. Design Retrospective cohort study design. Methods and results A total of 11 210 394 subjects (6 198 542 men and 5 011 852 women) >20 years of age were enrolled in this study. Weight change over 4 years divided into seven categories from weight loss ≥15% to weight gain ≥15%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of HF were analysed. The HR of HF showed a slightly reverse J-shaped curve by increasing weight change in total and >15% weight loss shows the highest HR (HR 1.647) followed by −15 to −10% weight loss (HR = 1.444). When using normal body mass index with stable weight group as a reference, HR of HF decreased as weight increased in underweight subjects and weight gain ≥15% in obesity Stage II showed the highest HR (HR = 2.97). Sustained weight for 4 years in the underweight and obesity Stages I and II increased the incidence of HF (HR = 1.402, 1.092, and 1.566, respectively). Conclusion Both weight loss and weight gain increased HR for HF. Sustained weight in the obesity or underweight categories increased the incidence of HF.

Background: Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea. METHODS: Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities. RESULTS: Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P

High lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults.A total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR).Among the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725-0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679-2.158).Serum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.

Background It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes. Methods Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis. Results The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, Pl0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, Pl0.001 and r=0.077, Pl0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, Pl0.001 and r=-0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006). Conclusion Transferrin is positively associated with incident type 2 diabetes in Koreans.

OBJECTIVE Previous studies have suggested that diabetes increases the risk of Parkinson disease (PD); however, this has not been conclusively established. We analyzed the risk of PD based on baseline glucose tolerance status in a large-scale cohort representative of the general Korean population. RESEARCH DESIGN AND METHODS This analysis was performed in a cohort of 15,168,021 adults aged ≥40 years who underwent health checkups under the National Health Insurance Service between January 2009 and December 2010. The clinical course of subjects was monitored until December 2016. Subjects were classified into the following groups: no diabetes, impaired fasting glucose (IFG), diabetes duration RESULTS During the observation period of 49,076,148.74 person-years, PD occurred in 31,577 patients. Compared with the nondiabetes group, the adjusted hazard ratio was 1.038 (95% CI, 1.009–1.067) in the IFG group, 1.185 (95% CI, 1.143–1.229) in the diabetes duration CONCLUSIONS This population-based cohort study suggests that diabetes is an independent risk factor for PD.

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

BackgroundAlthough autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD).MethodsA total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed.FindingsA total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85–0.96), 0.83 (0.78–0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up.ConclusionsOverall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.

Purpose Obesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration. Methods This was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, Pl0.001). Results Serum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, Pl0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, Pl0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, Pl0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration. Conclusion Hyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.

Purpose Bone plays a role in glucose metabolism through the release of uncarboxylated osteocalcin into the systemic circulation. The identified novel roles for osteocalcin include increasing insulin secretion and sensitivity, energy expenditure, reduction of fat mass, and mitochondrial proliferation and functional enhancement. This study aimed to determine serum osteocalcin levels in overweight children and to investigate the relationships of osteocalcin with glucose metabolism and insulin sensitivity. Methods After overnight fasting, serum osteocalcin levels were measured in overweight (n=50) children between 6.0 and 12.9 years of age and nonoverweight controls (n=60). Height, weight, fasting serum glucose, insulin, alkaline phosphatase, total cholesterol, and 25 hydroxy vitamin D3 (25(OH)VitD3) were also measured in all subjects. Results There were significant differences in serum osteocalcin levels between the overweight and control groups (64.00±20.44 vs. 89.56±28.63, Pl0.001). Serum osteocalcin levels were inversely correlated with body mass index (BMI) (r=-0.283, P=0.003), weight standard deviation score (SDS) (r=-0.222, P=0.020), BMI SDS (r=-0.297, P=0.002), insulin (r=-0.313, P=0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) index (r=-0.268, P=0.005). In the subsequent multiple regression analyses, BMI, HOMA-IR, and age were determined to be independent predicting factors for serum osteocalcin. Conclusion Our findings showed associations of serum osteocalcin with glucose metabolism and insulin sensitivity in overweight children, but we could not establish a causal relationship.

Background and aims Fibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD). We evaluate the association between baseline insulin resistance and future fibrosis progression in patients with NAFLD without diabetes. Approach and results This retrospective longitudinal study with 8-year follow-up period included 32,606 (men, 83%) participants aged >20 years (average age, 38.0 years) without diabetes at baseline who completed at least two comprehensive health checkups from January 1, 2010 to December 31, 2018. NAFLD was diagnosed based on ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate baseline insulin resistance. Fibrosis progression was assessed using the aspartate aminotransferase to platelet ratio index (APRI). The advanced liver fibrosis with an APRI value above the intermediate fibrosis probability (≥0.5) developed in a total of 2,897 participants during 136,108 person-years. 114 participants progressed to a high fibrosis probability stage (APRI >1.5) during 141,064 person-years. Using the lowest baseline HOMA-IR quartile group (Q1) as a reference, the multivariate-adjusted hazard ratio (HR) for development of advanced liver fibrosis (APRI ≥0.5) in the highest baseline HOMA-IR quartile group (Q4) was 1.95 (95% confidence interval [CI] 1.74–2.19; Model 4). And the HR for development of advanced liver fibrosis with high fibrosis probability was 1.95 (95% CI 1.10–3.46; Model 4). The positive association was maintained throughout the entire follow-up period. The baseline HOMA-IR model was superior to the baseline body mass index (BMI) model in predicting the progression of fibrosis probability. Conclusions In this longitudinal study, we found that the degree of baseline insulin resistance, assessed by HOMA-IR values, was positively associated with future fibrosis progression in patients with NAFLD without diabetes.

Coronary artery calcification (CAC) is a feature of coronary atherosclerosis and a well-known risk factor for cardiovascular disease (CVD). As the absence of CAC is associated with a lower incidence rate of CVD, measurement of a CAC score is helpful for risk stratification when the risk decision is uncertain. This was a retrospective study with an aim to build a model to predict the presence of CAC (i.e., CAC score = 0 or not) and evaluate the discrimination and calibration power of the model. Our data set was divided into two set (80% for training set and 20% for test set). Ten-fold cross-validation was applied with ten times of interaction in each fold. We built prediction models using logistic regression (LRM), classification and regression tree (CART), conditional inference tree (CIT), and random forest (RF). A total of 3302 patients from two cohorts (Soonchunhyang University Cheonan Hospital and Kangbuk Samsung Health Study) were enrolled. These patients&rsquo, ages were between 40 and 75 years. All models showed acceptable accuracies (LRM, 70.71%, CART, 71.32%, CIT, 71.32%, and RF, 71.02%). The decision tree model using CART and CIT showed a reasonable accuracy without complexity. It could be implemented in real-world practice.

Vascular calcification increases the risk of developing cardiovascular disease, and it is closely associated with metabolic disorders such as diabetes mellitus and non-alcoholic fatty liver disease. We investigated whether the activators of AMP-activated protein kinase (AMPK), metformin, resveratrol, and exendin-4, improved inorganic phosphate (Pi)-induced vascular calcification in rat vascular smooth muscle cells (VSMCs) and whether these effects were via AMPK. Pi increased calcium deposition in a dose-dependent manner, and metformin, resveratrol, and exendin-4 significantly decreased calcium deposition in the Pi-treated VSMCs. Moreover, metformin and exendin-4 increased the expression of a SMC marker gene, α-smooth muscle actin, and Ampk and reduced the receptor activator of nuclear factor kappa-Β ligand (Rankl)/osteoprotegerin ratio. Metformin, resveratrol, and exendin-4 reduced the expression of osteoblast differentiation-associated factors, such as runt-related transcription factor 2, bone morphogenic protein-2, p-small mothers against decapentaplegic 1/5/8, and Rankl. Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs. These data suggest that metformin, resveratrol, and exendin-4 ameliorate Pi-induced vascular calcification by inhibiting osteoblast differentiation of VSMCs, which is mediated by AMPK.

Background: High blood glucose level has a linear relationship with all-cause mortality. However, the influence of glycemic abnormality on mortality differs by age group. We aimed to analyze all-cause mortality according to glycemic status, age groups, and comorbidities using a national health database. Methods: The 6,330,369 participants who underwent Korean National Health Screening in 2009 were followed up until 2016, with a median follow-up of 7.3 years. All-cause mortality rates were analyzed according to glycemic status (normoglycemia, impaired fasting glucose [IFG], newly diagnosed diabetes, diabetes duration &lt, 5 years, diabetes duration &ge, 5 years), age groups (20&ndash, 39, 40&ndash, 65, and &ge, 65 years), and comorbidities using the Korean National Health Insurance System database. Results: At baseline, 712,901 (11.3%) subjects had diabetes. Compared with subjects without diabetes, those with diabetes at baseline showed increased mortality risk after adjustment for multiple risk factors (hazard ratio [HR] 1.613, 95% confidence interval [CI] 1.598,1.629), and those with IFG showed a significantly increased mortality risk compared with normoglycemic subjects (HR 1.053, 95% CI 1.042,1.064). Mortality risk associated with glycemic status decreased gradually from younger to older age groups and was consistently higher in those with diabetes with coronary heart disease, ischemic stroke or decreased renal function than those without comorbidities. Conclusion: Compared with normoglycemic subjects, subjects with diabetes and IFG had an increased mortality risk and the mortality risk was higher in the younger age group than in the older age group. The presence of diabetes and comorbid diseases synergistically increased mortality risk.

Smoking cessation reduces the cardiovascular risk but increases body weight. We investigated the risk of subsequent myocardial infarction and ischemic stroke according to weight gain after smoking cessation, using a nationwide population based cohort. We enrolled 3,797,572 Korean adults aged over 40 years who participated in national health screenings between 2009 and 2010. Subjects who quit smoking were classified into three subgroups according to the weight change between baseline and 4 years prior. Myocardial infarctions and ischemic strokes were followed until the end of 2015. We compared the hazard ratios among smoking cessation subgroups, non-smokers, and current smokers. The mean changes in weight (1.5 ± 3.9 kg) of the smoking cessation group were higher than those of the other groups (p < 0.0001). A total of 31,277 and 46,811 subjects were newly diagnosed with myocardial infarction and ischemic stroke, respectively. Regardless of weight change, all subgroups of smoking cessation had significantly less risk than current smokers. The subgroup of smoking cessation with weight gain over 4kg showed the lowest risk for myocardial infarctions (hazard ratio 0.646, 95% confidence interval 0.583–0.714, p < 0.0001) and ischemic strokes (hazard ratio 0.648, 95% confidence interval 0.591–0.71, p < 0.0001) after multivariable adjustment. In conclusion, weight gain after smoking cessation did not adversely affect the cardiovascular protective effect.

Purpose This study aimed at investigating whether there is a continuous dose-response relationship between the amount of physical activity (PA) and longevity benefit. Methods We evaluated the records of 23,257,723 Koreans age ≥20 yr who had undergone one biennial medical evaluation by the National Health Insurance Corporation. Participants with ≥20 min of vigorous or ≥30 min of moderate PA or walking were stratified into four groups: 0 d·wk; 1-3 d·wk; 4 to 5 d·wk; and 6-7 d·wk. After calculating total metabolic equivalent task-hours per week (MET·h·wk), we created eight categories of MET-hours per week (0, 0.1-4.9, 5.0-9.9, 10.0-14.9, 15.0-19.9, 20.0-24.9, 25.0-29.9, and ≥30.0). Multivariate Cox proportional hazard analyses were performed. Results A reverse J-shaped risk curve was observed, with the lowest mortality risk in the participants exercising 4 to 5 d·wk (reference). Participants who did not exercise at all and those who exercised with a PA frequency of 1 to 3 d·wk or 6 to 7 d·wk showed a significantly increased mortality risk compared with the reference group. When we repeated the Cox analysis among the 8 MET·h·wk categories with the participants reporting 20.0 to 24.9 MET·h·wk of PA as the reference group, we found that those with physical inactivity and 25.0-29.9 or ≥30.0 MET·h·wk of PA showed a higher mortality risk than the reference group. These relationships were persistently observed after adjustment for confounders. Conclusions An appropriate amount of regular exercise in each specific type of PA was associated with the lowest risk of mortality. The inactive participants showed an increased mortality risk, and daily PA did not show any additional benefit in the mortality risk.

The presence of abdominal obesity and lack of physical activity are both risk factors for the development of hypertension. The aim of this study was to analyze the risk of developing hypertension according to baseline waist circumference (WC). In total, 16 312 476 non-hypertensive participants who were covered by the National Health Insurance Service (NHIS) from 2009 to 2012 in Korea were included in the study. The participants were divided into six groups according to the level of baseline WC with a 5-cm interval starting from 80 cm in men and 75 cm in women. The risk for the future development of hypertension was assessed in 2015 using the claims data on the diagnosis of hypertension and prescription of anti-hypertensive medications. Approximately 7.8% of the participants developed hypertension over a median follow-up of 5.48 years. The proportion of participants who developed hypertension significantly increased from 4.2% in the WC level 1% to 17.5% in the WC level 6. After adjusting for confounding factors, level 6 of the baseline WC had a higher hazard ratio (HR) for the development of hypertension among the 6 levels of baseline with level 3 as the reference (1736; 95% confidence interval [95% CI]: 1.72-1.753). The participants with abdominal obesity had a significantly higher HR than those without abdominal obesity regardless of whether they engage in high- or moderate-intensity physical intensity (1.741; 95% CI: 1.718-1.764). WC had a linear association with the development of hypertension based on this large nationwide population-based cohort study, which was not influenced by physical activity.

Objective Thyroid hormones play crucial roles in the control of energy homoeostasis and can influence body composition. In contrast, the changes in body composition might influence thyroid hormone levels. We evaluated associations between thyroid hormone levels, body composition and insulin resistance in euthyroid subjects with normal thyroid ultrasound (US) findings. Design and patients This retrospective cross-sectional study included 36 655 euthyroid subjects who joined the medical health check-up programme at our institution. Serum thyroid hormone levels were analysed in association with body fat percentage (BFP), skeletal muscle mass index (SMI) and homoeostatic model assessment of insulin resistance (HOMA-IR). Linear regression analyses were performed to evaluate relationships between thyroid hormone levels and anthropometric parameters. Results Mean age was 36.4 years, and 49% of subjects were female. In multiple linear regression analysis, serum-free triiodothyronine (FT3) levels exhibited positive associations with waist circumference (WC) and HOMA-IR and a negative association with body weight, body mass index (BMI) and SMI among both men and women. The association between serum-free thyroxine (FT4) levels and anthropometric markers showed inconsistent results in men and women. Serum thyroid-stimulating hormone (TSH) levels showed a positive association with HOMA-IR in both men and women. Conclusions Lower SMI was significantly associated with higher serum FT3 levels, the active form of thyroid hormone, in both men and women. Higher insulin resistance was positively associated with serum FT3 levels and inversely associated with serum TSH levels in euthyroid subjects with normal thyroid US findings.

Insulin resistance and inflammation play an important role in a variety of chronic diseases.We investigated the influence of systemic inflammation on the relationship between insulin resistance and mortality risk in apparently healthy adults.This study examined the mortality outcomes for 165,849 Koreans enrolled in a health-screening program. The subjects were divided into four groups according to their homeostatic model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) levels: group 0, HOMA-IR75% and hs-CRP2.0mg/L; group 1, HOMA-IR ≥75% and hs-CRP2.0mg/L; group 2, HOMA-IR75% and hs-CRP ≥2.0mg/L; and group 3, HOMA-IR ≥75% and hs-CRP ≥2.0mg/L. The Cox proportional hazard models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease, and cancer-related mortality.During the follow-up period of 1,417,325.6person-years, a total of 1316 deaths (182 from cardiovascular disease) occurred. The multivariate-adjusted HRs for all-cause mortality were significantly higher in groups 2 (HR 1.40; 95% CI: 1.19-1.64) and group 3 (HR 1.68; 95% CI: 1.34-2.10) than that in group 0. For cardiovascular mortality, the sex-adjusted hazards were also significantly higher in groups 2 and 3 than that in group 0; however, this increased risk disappeared during multivariate analysis. Groups 2 and 3 had significantly higher risk for cancer-related mortality than group 0, with multivariate-adjusted hazard ratios of 1.48 (95% CI: 1.18-1.86) and 1.84 (95% CI: 1.35-2.51), respectively.Systemic inflammation can be used to stratify the subjects according to the all-cause and cancer-related mortality risks, irrespective of the insulin-resistance status. And this tendency is most pronounced in cancer-related mortality.

Background : The prevalence of obesity and related comorbidities is increasing worldwide, including in Korea. The Korean Society for the Study of Obesity released the Obesity Fact Sheet 2017 to address this problem in the Korean population. Methods : Data from the National Health Insurance Service Health Checkup database from 2006 to 2015 were standardized by age and sex using the 2010 Census. The definition of obesity was a body mass index (BMI) ≥25 kg/m², and that of abdominal obesity was a waist circumference ≥90 cm in men and ≥85 cm in women. Multivariate adjusted Cox regression analysis was conducted, and hazard ratios (HRs) with 95% confidence intervals were calculated for comorbidities. Results : From 2009 to 2015, the prevalence of obesity increased from 29.7% to 32.4%, and that of abdominal obesity increased from 18.4% to 20.8%. Obesity with abdominal obesity also increased from 15.1% to 17.7%. Between 2014 and 2015, the prevalence of obesity increased until 30–40 years of age, but decreased from 40–50 years of age in men. In women, it increased until the mid-70s, and decreased thereafter. Abdominal obesity increased from 20–30 years of age to 70–80 years of age, but decreased thereafter. The HRs for type 2 diabetes mellitus, hypertension, dyslipidemia, myocardial infarction, and ischemic stroke were elevated in subjects with abdominal obesity, and their incidence increased as the BMI increased, but slowed down at BMI ≥35 kg/m². Conclusion : Based on the Obesity Fact Sheet 2017, strategies for reducing the prevalence of obesity and abdominal obesity are essential.

Osteocalcin is the non-collagenous protein produced by osteoblasts in bone. When it is released into systemic circulation in its uncarboxylated form, it regulates fat and glucose metabolism. Recent studies have shown that osteocalcin is also involved in male fertility. Because the onset of puberty is determined by ethnic, genetic, environmental, and metabolic factors, we focused on determining the role of osteocalcin in the onset of puberty. Central precocious puberty (CPP) is defined as the activation of the hypothalamic-pituitary-gonadal axis before the age of 8 in girls and 9 in boys. CPP is diagnosed when peak luteinizing hormone (LH) reaches ≥ 5.0 IU/l after stimulation with gonadotropin-releasing hormone (GnRH). This retrospective study included 206 girls who showed breast budding before the age of 8 and whose bone age was more advanced than their chronological age. The CPP group included 100 girls who were diagnosed with CPP, and 106 girls were the non-CPP group whose peak LH did not reach ≥ 5.0 IU/l after GnRH stimulation test. Serum osteocalcin levels were measured to investigate the relationship between osteocalcin and the onset of puberty. Our data showed that serum osteocalcin levels were significantly higher in the CPP group (87.7 ± 24.4 ng/ml vs. 68.3 ± 19.5 ng/ml, P < 0.001). The multivariate analysis revealed that an increase in bone age and peak LH was significantly associated with the serum osteocalcin level. The results of this study suggest that serum osteocalcin is associated with the onset of puberty in girls.

Spermatogenesis begins after puberty and continues throughout a male's life, and is regulated by spermatogonial stem cells in the seminiferous tubules. Markers of male germ cells, including undifferentiated spermatogonia to fully developed spermatozoa have been identified in rodents, but not in dogs. In this study, to characterize the markers of undifferentiated spermatogonia, histological and immunohistochemical analyses were performed on pre-pubertal (1-month-old), early pubertal (4-month-old), and post-pubertal (7-month-old) dog testes. Expression of chemokine receptor 4 (CXCR4), insulin-like growth factor binding protein 3 (IGFBP3), LIN28, and Sal-like protein 4 (SALL4) genes was confirmed by immunohistochemical analysis. In pre-pubertal and early pubertal dog testes, CXCR4, IGFBP4, and LIN28 genes were expressed in undifferentiated spermatogonia, whereas the SALL4 gene was not expressed in the pre-pubertal stage. In adult dog testes, CXCR4 and IGFBP3 gene expression was detected in undifferentiated spermatogonia and co-localized with protein gene product 9.5 (PGP9.5) near the basement membrane of the seminiferous tubules. The LIN28 and SALL4 genes were expressed in synaptonemal complex protein 3-positive spermatocytes. The CXCR4 and IGFBP3 gene expression is conserved among other species, while LIN28 and SALL4 gene expression varies. Based on results of the present study, it is suggested that undifferentiated spermatogonia markers detected in other species are conserved in dogs. These results may facilitate further studies of the cellular mechanisms of spermatogenesis in dogs.

Background and Aim Previous studies reported that many patients are at high risk for cardiovascular disease (CVD) despite achieving recommended low-density lipoprotein cholesterol (LDL-C) levels. Therefore, we investigated whether the association between LDL-C and the risk for incident CVD differed according to high-density lipoprotein cholesterol (HDL-C) levels using coronary artery calcium score (CACS) progression as a surrogate marker for predicting CVD. Methods We investigated 2132 Korean men in a health screening program, in which CACS was measured at baseline and after 4 years. Coronary artery calcification (CAC) progression was defined as a change in CACS ≥0 over 4 years. We divided the subjects into nine groups according to baseline HDL-C and LDL-C levels and compared their risks for CAC progression. Results After 4 years, 475 subjects (22.3%) exhibited CAC progression. We identified a positive relationship between baseline LDL-C levels and the risk for incident CAC. However, this association was attenuated by high baseline HDL-C levels. Multivariate logistic regression analysis adjusted for age, body mass index, systolic blood pressure, fasting glucose, smoking, and exercise status revealed that the odds ratios for incident CAC in the lowest HDL-C tertile were 3.08 for LDL-C tertile 3 and 2.02 for LDL-C tertile 2 compared to LDL-C tertile 1. However, these differences disappeared in the highest HDL-C tertile (HDL-C ≥54.0 mg/dL). Conclusions In this longitudinal study, we found that the positive relationship between LDL-C and the relative risk for incident CAC was attenuated by higher HDL-C levels. Therefore, HDL-C levels should be considered when estimating CVD risk.

Purpose Insulin resistance is one of the most important mechanisms in the development of diabetes, and it is closely related to the presence and severity of coronary heart disease. Triglyceride glucose (TyG) index is a useful marker of insulin resistance; however, few studies have investigated the relationship between TyG and subclinical atherosclerosis. Therefore, we evaluated the association of TyG and subclinical coronary atherosclerosis as measured by coronary artery calcium score (CACS). Methods Our study included 30,776 participants (mean age of 41 years, 80.4% male) enrolled in a health screening program, in whom CACS were measured. Homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-body mass index (BMI), and TyG-waist circumference (WC) were subsequently analyzed. Indices were calculated using the following formulae: HOMA-IR=fasting insulin (μU/mL)×fasting plasma glucose (FPG; mmol/L)/22.5; TyG index=Ln [TG (mg/dL)×FPG (mg/dL)/2]; TyG-BMI=TyG index×BMI; and TyG-WC=TyG index×WC. CACS was measured using multidetector computed tomography, and the presence of coronary artery calcification (CAC) was defined by CACS>0. Results The prevalence of CAC was 14.4% in the study population. Multivariate logistic regression analysis showed that participants with TyG-BMI in the highest tertile were 1.638 times more likely to have CAC after adjustment for other metabolic parameters compared with participants with TyG-BMI in the lowest tertile (odds ratio, 1.612; 95% confidence interval, 1.465 to 1.774). The receiver operating characteristics curve for prediction of CAC showed that TyG-WC index had a higher area under the curve (AUC=0.626) than other indices (AUCTyG=0.617, AUCTyG-BMI=0.616, AUCHOMA-IR=0.562). Conclusion TyG index predicted CAC better than other markers of insulin resistance, and could be a useful marker for predicting subclinical atherosclerosis.

Because the rate of bone loss is an important risk factor for fracture, we studied longitudinal changes in bone mineral density (BMD). Although the BMD of the hip decreased over time, spine BMD remained largely stable or increased. Therefore, spine BMD may not be appropriate for assessing BMD change. The rate of age-dependent bone loss has been shown to be an important risk factor for fracture. However, longitudinal rates of BMD loss in Korea have not yet been reported. The objective of this study was to evaluate longitudinal changes in BMD in Korea. This cohort study was performed in a population of individuals 40 years of age or older living in the rural area of Chungju City, Korea. A second BMD examination was conducted approximately 4 years after a baseline examination. A total of 3755 of the 6007 subjects completed the follow-up visit, corresponding to a follow-up rate of 62.51%. The age-standardized osteoporosis prevalence was 12.81% in males and 44.35% in females. In males, the average annual BMD loss at the total hip increased from −0.25% per year in their 40s to −1.12% per year in their 80s. In females, the average annual BMD loss at the total hip increased from −0.69% per year in their 40s to −1.51% per year in their 80s. However, the average annual percentage change in spine BMD in females increased from −0.91% per year in their 40s to +1.39% per year in their 80s. A substantial number of subjects had osteoporosis, even though we standardized the prevalence of osteoporosis. In total hip, the mean BMD was decreased during the follow-up period; in addition, the annual percentage loss increased with age. However, spine BMD remained approximately stable or increased over time and therefore may not be appropriate for assessing BMD change.

Backgrounds and aims Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians. Decreased muscle mass is one of the major causes of chronic disease in adults. The purpose of this study was to analyze the relationship between muscle mass and ICAS in Korean adults. Methods For this study, we selected a total of 10,530 participants (mean age, 43.3 years; 8558 men) in a health screening program, for whom transcranial Doppler (TCD) ultrasound was used to detect >50% ICAS based on criteria modified from the stroke outcomes and neuroimaging of intracranial atherosclerosis trial. Body composition was evaluated by bioelectrical impedance analysis (BIA). Skeletal muscle index (SMI) was calculated with muscle mass/weight (kg) * 100. Results Among the total patient population, 322 (3.1%) subjects had ICAS. Subjects with ICAS were older, and had higher mean values for fasting glucose, body mass index and blood pressure compared with those without ICAS. Subjects with ICAS had significantly lower muscle mass, SMI and higher percent body fat compared with those without ICAS. In logistic regression analysis, the subjects in the highest tertile of muscle mass had the lowest odds ratio for ICAS with the lowest tertile group of muscle mass as the reference group even after adjusting for age, systolic blood pressure, fasting blood glucose, sex, smoking and exercise (OR 0.650, 95% CI 0.442–0.955). Conclusions Subjects with ICAS had significantly decreased muscle mass compared with those without ICAS in Korean adults. The risk for ICAS was lower in subjects with higher muscle mass.

OBJECTIVE The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians. RESEARCH DESIGN AND METHODS A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group. RESULTS During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70–0.95], 0.76 [0.65–0.90], and 0.78 [0.67–0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21–1.65], 1.32 [1.13–1.53], and 1.31 [1.13–1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance. CONCLUSIONS Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.

No cohort studies have evaluated the effect of obesity on the incidence of thyroid cancer according to metabolic health status. Therefore, this study examined the association of body mass index (BMI) and metabolic health status with thyroid cancer risk.A cohort study was performed involving 255,051 metabolically healthy (MH) and metabolically unhealthy (MUH) adults free of thyroid cancer at baseline who were followed for a median of 5.3 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and confidence interval (CI).During 1,402,426.3 person-years of follow-up, 2927 incident thyroid cancers were identified. Among men, the multivariable aHR for thyroid cancer comparing obesity, defined as a BMI ≥25 kg/mIn both MH and MUH men, obesity was associated with an increased risk of incident thyroid cancer, indicating excessive adiposity per se as an independent risk factor for thyroid cancer. Conversely, women with MUH obesity but not MH obesity were found to have an increased risk of thyroid cancer, indicating that obesity with accompanying metabolic abnormalities may affect thyroid cancer risk in women.

Background We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults. Methods Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: 25 kg/m2 (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0. Results When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]). Conclusion Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.

Results from previous studies support the association of lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we analyzed the association between baseline Lp(a) levels and future progression of coronary artery calcification (CAC) in apparently healthy Korean adults.A total of 2611 participants (mean age: 41years, 92% mend) who underwent a routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a) was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC was defined as a change in CACS0 over four years.Bivariate correlation analyses with baseline Lp(a) and other metabolic parameters revealed age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive correlation, while body weight, fasting glucose level, blood pressure and triglyceride level were negatively correlated with baseline Lp(a) level. After four years of follow-up, 635 subjects (24.3%) had CAC progression. The participants who had CAC progression were older, composed of more men, more obese, and had higher fasting glucose levels and worse baseline lipid profiles compared to those who did not have CAC progression. The mean serum Lp(a) level was significantly higher in subjects who had CAC progression compared to those who did not (32.5 vs. 28.9mg/dL, p0.01). When the risk for CAC progression according to baseline Lp(a) was calculated, those with Lp(a) level≥50mg/dL had an odds ratio of 1.333 (95% CI 1.027-1.730) for CAC progression compared to those with Lp(a)50mg/dL after adjusting for confounding factors.In this study, the subjects who had higher Lp(a) were at significantly higher risk for CAC progression after four years of follow-up, suggesting the role of high Lp(a) in CAC progression.

Background The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults. Methods Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR

Background Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans. Methods This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline. Results Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014). Conclusion C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults.For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high-density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography.CACS was positively correlated with VAI (r = 0.027, p 0.001). Subjects with 0 CACS100 and CACS ≥ 100 had significantly higher VAI compared to those with CACS = 0 (2.04 ± 1.97, 2.08 ± 1.67 vs. 1.68 ± 1.50, p 0.001). In logistic regression analyses with CACS0 as the dependent variable, subjects in the highest tertile of VAI (1.777) had significantly increased odds ratio for CACS0 compared to subjects in the lowest tertile (0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381).Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis.

Objective Coronary artery calcification (CAC) is considered a surrogate marker for atherosclerotic burden. The aim of this study was to analyze the risk of incident CAC associated with diabetes development in non-diabetic subjects with zero CAC score (CACS) at baseline. Methods 2076 non-diabetic participants (mean age 40 years) in a health screening program in whom CACS were repeatedly measured by multi-detector computed tomography in four years of intervals and with zero CACS at baseline, were retrospectively analyzed. Glycemic status was assessed in both years, with subjects divided into three groups: subjects with ‘no progression’, ‘normal to impaired fasting glucose (IFG)’ and ‘progression to diabetes’. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR) index. Results Over 4 years, 204 subjects (9.8%) developed CAC. Subjects who developed diabetes showed the highest proportion of subjects with incident CAC among the three groups (21.0% vs. 9.3 and 10.4% in non-progressors and subjects from normal to IFG). The subjects with HOMA-IR level in higher half at baseline showed significantly increased risk for incident CAC in subjects who progressed from normal to IFG and in subjects who developed diabetes (1.740; 95% CI 1.014–2.985, 2.449; 95% CI 1.159–5.174) even after adjustment for confounding variables, whereas subjects with HOMA-IR level in lower half at baseline showed no significantly increased risk for incident CAC even in subjects who developed diabetes. Conclusions In this non-diabetic population, we found that increased risk for incident CAC in relation to diabetes development over 4 years was pronounced only in subjects with insulin resistance at baseline.

Objective Diabetes and prediabetes subjects have increased risk for mortality. We analyzed the mortality risk due to all causes, cardiovascular disease (CVD) and cancer in Korean subjects participating in a health-screening program according to baseline glycemic status and HbA1c levels. Materials/methods Among 241,499 participants of a health-screening program between 2005 and 2012, the risk of death from all causes, CVD, and cancer was calculated based on the baseline glycemic status (normoglycemia, prediabetes, and diabetes) and HbA1c levels. Uncontrolled diabetes was defined as HbA1c ≥ 7.0%. Vital status and confirmation of the cause of death were based on the analysis of death certificate records from the National Death Index. Results During 923,343.1 person-years of follow-up, 877 participants died. The multivariable-adjusted hazard ratios (HR) of subjects with controlled and uncontrolled diabetes to normoglycemic subjects for all-cause mortality were 1.58 (95% CI 1.24–2.03) and 2.26 (95% CI 1.78–2.86), respectively. The HRs of subjects with controlled and uncontrolled diabetes to normoglycemic subjects for mortality due to cancer were 1.75 (95% CI 1.23–2.48) and 1.67 (95% CI 1.13–2.45). However, glycemic status was not significantly associated with the risk of mortality due to CVD. The subjects with HbA1c higher than 6.5% showed more than 2-fold increased risk for all-cause mortality and the subjects with HbA1c lower than 5.2% showed increased HR (1.45, 95% CI 1.06–1.97) compared with those with HbA1c of 5.5% in subjects not taking anti-diabetic medications. Conclusions Mortality risk from all causes and cancer significantly increased in diabetes subjects regardless of the glucose control status. In subjects not taking anti-diabetic medications, both high and low HbA1c resulted in increased risk for all-cause mortality.

BACKGROUND Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status. METHODS We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively. RESULTS Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI

We would like to thank Melgoza et al. (1) for their interest in our article (2) and for suggesting the need for more analysis of the relationship of smoking and Parkinson disease (PD). They also suggested the importance of the cholinergic system in protection from PD and also stressed the need for discovery of novel drugs that target the cholinergic …

Background We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD. Methods This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high. Results The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects. Conclusion High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.