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Abstract Objective The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. Methods In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti‐dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. Results A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009–2010 and 2011–2012 were included. A 1‐kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84–0.87; aHR: 0.70, 95% CI 0.69–0.72, respectively for men, and aHR: 0.69, 95% CI 0.67–0.71; aHR: 0.59, 95% CI 0.57–0.61, respectively for women). A 1‐kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17–1.21 for men and aHR: 1.53, 95% CI 1.48–1.57 for women). These results remained consistent regardless of sex or weight change. Interpretation Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

Background/Aims To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. Methods Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. Results Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68–3.21; P

Background There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. Results Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], –0.17; 95% confidence interval [CI], –0.27 to –0.07). In the network meta-analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. Conclusion SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Abstract Major post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03–0.18) and decline (aMean − 0.60; 95% CI − 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16–1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31–0.45) and declined (aOR 0.17; 95% CI 0.13–0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors.

Abstract Despite many diabetic patients having hypercholesterolemia, the association of total cholesterol (TC) levels with CVD risk in type 2 diabetes (T2D) patients is unclear. Diagnosis of type 2 diabetes often leads to changes in total cholesterol (TC) levels. Thus, we examined whether changes in TC levels from pre- to post-diagnosis of T2D were associated with CVD risk. From the National Health Insurance Service Cohort, 23,821 individuals diagnosed with T2D from 2003 to 2012 were followed-up for non-fatal CVD incidence through 2015. Two measurements of TC, 2 years before and after T2D diagnosis, were classified into 3 levels (low, middle, high) to define changes in cholesterol levels. Cox proportional hazards regression was performed to estimate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs) for the associations between changes in cholesterol levels and CVD risk. Subgroup analyses were performed by use of lipid-lowering drugs. Compared with low–low, aHR of CVD was 1.31 [1.10–1.56] for low–middle and 1.80 [1.15–2.83] for low–high. Compared with middle–middle, aHR of CVD was 1.10 [0.92–1.31] for middle–high but 0.83 [0.73–0.94] for middle–low. Compared with high–high, aHR of CVD was 0.68 [0.56–0.83] for high–middle and 0.65 [0.49–0.86] for high–low. The associations were observed regardless of use of lipid-lowering drugs. For diabetic patients, management of TC levels may be important to lower CVD risk.

Abstract Hemoglobin variability is known to increase cardiovascular mortality in chronic kidney disease, but the association of hemoglobin variability with the risk of cardiovascular disease (CVD) in the general population is yet unclear. This retrospective cohort study based on ‘the South Korean National Health Insurance Service database’ consisted of 198,347 adults who went through all three health examinations. Hemoglobin variability is defined as the average successive variability of three separate hemoglobin values from each health screening period. Participants were followed up for 6 years to determine the risk of coronary heart disease and stroke. We used multivariate Cox proportional hazards regression to examine the adjusted hazard ratios for CVD according to hemoglobin variability. Per 1 unit increase of hemoglobin variability, the risk for CVD (aHR 1.06, 95% CI 1.02–1.09) and stroke (aHR 1.08, 95% CI 1.03–1.13) increased significantly. The risk-increasing trend was preserved in the low-to-moderate risk group of CVDs (aHR 1.07, 95% CI 1.02–1.11). This result suggests that subjects with high hemoglobin variability who would otherwise be categorized as having low-to-moderate CVD risk may have higher risk of CVD than those with low hemoglobin variability.

Background/Aims: Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined. Methods: This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression. Results: Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change. The liver enzyme levels were higher among participants with smoking cessation and BMI gain. Conclusions: Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.

Abstract Glycemic variability (GV) is a risk factor for depression in patients with diabetes. However, whether it is also a predictor of incident depression in people without diabetes remains unclear. We aimed to investigate the association between visit-to-visit variability in fasting serum glucose (FSG) levels and the incidence of depression among Koreans without diabetes. This retrospective cohort study included data of people without diabetes who did not have depression at baseline and had at least three FSG measurements (n = 264,480) extracted from the 2002–2007 Korean National Health Insurance Service–National Health Screening Cohort. GV was calculated as the average successive variability of FSG. Among 264,480 participants, 198,267 were observed during 2008–2013 and their hazard ratios (HR) of incident depression were calculated. Participants with the highest GV showed a higher risk of depression in fully adjusted models than those with the lowest GV (HR, 1.09; 95% CI, 1.02–1.16). The risk of incident depression heightened with increasing GV (p for trend

Background/Aims: Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed. Methods: This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term. Results: This study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD. Conclusions: Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.

Background/Aims Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia. Methods The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia. Results During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI

Abstract A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68–0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62–0.85) but not ICC (aHR, 0.95; 95% CI 0.73–1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62–0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52–0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71–1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71–1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44–0.81) and 0.77 (95% CI 0.64–0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63–0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.

Abstract There is growing evidence that suggests a potential association between particulate matter (PM) and suicide. However, it is unclear that PM exposure and suicide death among major depressive disorder (MDD) patients, a high-risk group for suicide. We aimed to assess the effect of short-term exposure to PM on the risk of suicide in MDD patients who are at high risk for suicide. We investigated the risk of suicide among 922,062 newly-diagnosed MDD patients from 2004 to 2017 within the Korean National Health Insurance Service (NHIS) database. We identified 3,051 suicide cases from January 1, 2015, to December 31, 2017, within the death statistics database of the Korean National Statistical Office. PMs with aerodynamic diameter less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 2.5–10 μm (PM2.5–10) were considered, which were provided from the National Ambient Air Monitoring System in South Korea. Time-stratified case-crossover analysis was performed to investigate the association of particulate matter exposure to suicide events. The risk of suicide was significantly high upon the high level of exposure to PM2.5, PM2.5–10 (coarse particle) and PM10 on lag 1 (p for trend

Abstract Background Little is known about the association of changes in two body components, muscle and fat mass, with the risk of cardiovascular disease (CVD) among young adults. We investigated the association of changes in predicted lean body mass index (LBMI), appendicular skeletal muscle mass index (ASMI), and body fat mass index (BFMI) with the development of CVD among young adults. Methods This nationwide, population‐based cohort study included 3 727 738 young adults [2 406 046 (64.5%) men and 1 321 692 (35.5%) women] aged 20–39 years without a previous history of CVD who underwent two health screening examinations during 2009–2010 and 2011–2012. Using validated and robust prediction equations, we calculated the changes in predicted LBMI, ASMI, and BFMI from the first to the second examinations. Results The mean (SD) age was 32.2 (4.9) years, and 2 406 046 (64.5%) of the participants were men. A total of 23 344 CVD events were detected during 22 257 632 person‐years of follow‐up. Each 1 kg/m2 increase in predicted LBMI and ASMI change was associated with a reduced risk of CVD among men [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI) 0.82–0.91; aHR: 0.76, 95% CI 0.69–0.82, respectively] and women (aHR: 0.77, 95% CI 0.63–0.95; aHR: 0.75, 95% CI 0.59–0.96). Each 1 kg/m2 increase in predicted BFMI change was associated with an increased risk of CVD among men (aHR: 1.16, 95% CI 1.10–1.22) and women (aHR: 1.32, 95% CI 1.06–1.65). In both sexes, decreases in predicted LBMI and ASMI were associated with greater CVD risk, and decreased predicted BFMI was associated with a reduced CVD risk. Those who maintained their BMI between −1 and +1 kg/m2 also had a decreased risk of CVD per 1 kg/m2 increase in predicted LBMI and ASMI change among men (aHR: 0.86, 95% CI 0.80–0.92; aHR: 0.85, 95% CI 0.76–0.95) and women (aHR: 0.62, 95% CI 0.47–0.83; aHR: 0.59, 95% CI 0.44–0.80) and had a greater risk of CVD per 1 kg/m2 increase in predicted BFMI change among men (aHR: 1.17, 95% CI 1.10–1.25) and women (aHR: 1.64, 95% CI 1.20–2.23). Regardless of changes in weight, such as from normal to obese or vice versa, these results were consistent. Conclusions Among young adults, increased predicted muscle mass or decreased predicted fat mass were associated with a reduced risk of development of CVD. Decreased predicted muscle mass or increased predicted fat mass were associated with an elevated risk of development of CVD.

Abstract Background Obesity is protective of bone health; however, abdominal obesity is associated with a higher fracture risk. Little is known about whether body composition protects or adversely affects osteoporotic fractures because of practical issues regarding assessment tools. This study aimed to evaluate the association of predicted body composition with fracture risk to determine the distinctive and differing effects of muscle or fat mass on bone health outcomes in the general population. Methods This population‐based, longitudinal cohort study used 2009–2010 Korean National Health Insurance Service data and follow‐up data from 1 January 2011 to 31 December 2013, to determine the incidence of osteoporotic fracture (total, spine, and non‐spine) defined using the International Classification of Diseases, Tenth Revision codes. The study participants were aged ≥50 years (men, 158 426; women, 131 587). The predicted lean body mass index (pLBMI), appendicular skeletal muscle index (pASMI), and body fat mass index (pBFMI) were used to assess body composition, using anthropometric prediction equations. Results Over a 3 year follow‐up, we identified 2350 and 6175 fractures in men and women, respectively. The mean age of the participants was 60.2 ± 8.3 and 60.7 ± 8.4 years in men and women, respectively. In a multivariable‐adjusted Cox proportional hazards regression model, increasing pLBMI or pASMI was significantly associated with a decreased risk of total fractures in men and women. When comparing individuals in the lowest pLBMI and pASMI (reference groups), men with the highest pLBMI and pASMI had adjusted hazard ratios of 0.63 [95% confidence interval (CI) 0.47–0.83] and 0.62 (95% CI 0.47–0.82), and women with the highest pLBMI and pASMI had adjusted hazard ratios of 0.72 (95% CI 0.60–0.85) and 0.71 (95% CI 0.60–0.85), respectively, for total fractures. The pBFMI had no significant association with total fractures in men or women. Regarding sex‐specific or site‐specific differences, the protective effects of the pLBMI and pASMI on fractures were greater in men and reduced the risk of spinal fractures. An increased pBFMI was associated with an increased risk of spinal fractures in women. Conclusions An increased pLBMI or pASMI was significantly associated with decreased total osteoporotic fracture risk; however, the pBFMI showed no statistically significant association. Muscle mass was more important than fat mass in preventing future osteoporotic fractures based on anthropometric prediction equations.

Abstract Numerous studies have reported that antibiotics could lead to diabetes, even after adjusting for confounding variables. This study aimed to determine the causal relationship between antibiotics use and diabetes in a nationally representative cohort. This retrospective cohort study included adults aged 40 years or older who were enrolled in the Korean National Health Insurance Service-Health Screening Cohort. Antibiotic exposure was assessed from 2002 to 2005 and newly diagnosed diabetes mellitus was determined based on diagnostic codes and history of antidiabetic medication use from 2006 to 2015. Multivariate Cox proportional hazards model was used to assess the association between antibiotic use and diabetes incidence. The mean age of the 201,459 study subjects was 53.2 years. People who used antibiotics for 90 or more days had a higher risk of diabetes (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 1.07–1.26) compared to non-users. Those who used five or more classes of antibiotics had a higher risk of diabetes than those who used one antibiotic class (aHR 1.14; 95% CI 1.06–1.23). The clear dose-dependent association between antibiotics and diabetes incidence supports the judicious use of antibiotics in the future.

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia.Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer’s disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence.Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19–1.74], AD (aHR, 1.46; 95% CI, 1.17–1.81), and VD (aHR, 1.38; 95% CI, 0.83–2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00–1.66) and AD (aHR, 1.34; 95% CI, 1.00–1.78) than antibiotic non-users.Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.

Abstract Background There is no evidence whether it is best to stop drinking alcohol at all or whether it is okay to drink a little in that light-to-moderate alcohol use was associated with low cardiovascular disease (CVD) compared to non-drinker among colorectal cancer (CRC) survivors, who are regarded as vulnerable to CVD. Therefore, we evaluated the association between alcohol consumption and incident CVD among long-term survivors of CRC. Methods This population-based, retrospective cohort study utilized data from the Korean National Insurance Service of 20,653 long-term survivors of CRC diagnosed between 2006 and 2012. Participants were followed up to the date of CVD, death, or December 31, 2018. All patients were categorized according to their daily alcohol consumption (g/day). The outcomes were incident CVD, including ischemic heart disease (IHD) and ischemic and hemorrhagic stroke, analyzed using the Cox proportional hazards regression after adjusting for cardiovascular risk factors and history of chemotherapy and radiotherapy. Results There was no association between alcohol consumption and incident CVD among long-term survivors of CRC. Additionally, hazardous alcohol consumption (≥ 40 g/day in male patients and ≥ 20 g/day in female patients) was associated with increased CVD, ischemic stroke, and hemorrhagic stroke (adjusted hazard ratio [95% confidence interval]: 1.51 [1.15–1.97], 1.60 [1.03–2.48], and 2.65 [1.25–5.62], respectively) compared with non-drinkers. Conclusion No discernable protective association was found between alcohol consumption and incident CVD for even light-to-moderate drinking among long-term survivors of CRC. Alcohol consumption ≥40 g/day in male patients and ≥ 20 g/day in female patients was associated with an increased risk of stroke compared with non-drinkers. These novel results provide useful evidence when advising survivors of CRC regarding alcohol use.

Abstract The association of fluctuations in body mass index with cardiovascular risk in long-term is not well understood. This study aimed to investigate cardiovascular outcomes of weight fluctuation. Total of 67,101 obese adults from the Korean National Health Insurance Service who received health examinations in three separate biennial periods were included. Participants were followed up from January 1, 2008 to the date of cardiovascular disease, death, or December 31, 2015, and categorized into 9 distinctive groups according to the BMI. Continuous weight gain showed an increased risk of overall cardiovascular disease (hazard ratio [HR], 2.36; P = 0.007), whereas weight loss after weight maintenance (HR, 0.91; P = 0.016) and weight maintenance after weight loss (HR, 0.91; P = 0.004) were ameliorative compared to the no weight change group. As for coronary heart disease, weight maintenance after weight gain was unfavorable (HR, 1.25; P = 0.004) while weight loss after weight maintenance (HR, 0.82; P

Background The combined associations of physical activity and particulate matter (PM) with subsequent cardiovascular disease (CVD) risk is yet unclear. Methods and Results The study population consisted of 18 846 cancer survivors who survived for at least 5 years after initial cancer diagnosis from the Korean National Health Insurance Service database. Average PM levels for 4 years were determined in administrative district areas, and moderate‐to‐vigorous physical activity (MVPA) information was acquired from health examination questionnaires. A multivariable Cox proportional hazards model was used to evaluate the risk for CVD. Among patients with low PM with particles ≤2.5 µm (PM2.5; (19.8–25.6 μg/m3) exposure, ≥5 times per week of MVPA was associated with lower CVD risk (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.60–0.99) compared with 0 times per week of MVPA. Also, a higher level of MVPA frequency was associated with lower CVD risk (P for trend=0.028) among cancer survivors who were exposed to low PM2.5 levels. In contrast, ≥5 times per week of MVPA among patients with high PM2.5 (25.8–33.8 μg/m3) exposure was not associated with lower CVD risk (aHR, 0.98; 95% CI, 0.79–1.21). Compared with patients with low PM2.5 and MVPA ≥3 times per week, low PM2.5 and MVPA ≤2 times per week (aHR, 1.26; 95% CI, 1.03–1.55), high PM2.5 and MVPA ≥3 times per week (aHR, 1.34; 95% CI, 1.07–1.67), and high PM2.5 and MVPA ≤2 times per week (aHR, 1.38; 95% CI, 1.12–1.70) was associated with higher CVD risk. Conclusions Cancer survivors who engaged in MVPA ≥5 times per week benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk‐reducing effects of MVPA on the risk of CVD.

Abstract Background Ambient fine particulate matter is a rising concern for global public health. It was recently suggested that exposure to fine particulate matter may contribute to the development of diabetes and dyslipidaemia. This study aims to examine the potential associations of ambient particulate matter exposure with changes in fasting glucose and lipid profiles in Koreans. Method We used the data from the National Health Insurance Service–National Sample Cohort (NHIS-NSC), a nationwide database representative of the Korean population. A total of 85,869 individuals aged ≥20 years were included. Multiple regression analyses were conducted to assess the associations between exposure to particulate matter and changes in fasting glucose and lipid profiles at 2-year intervals after adjusting for confounders. Results Significant associations were observed between an increase in interquartile range for particulate matter

BackgroundConcerns about a growing number of colorectal cancer survivors have emerged regarding cardiovascular disease (CVD) risks. However, there is not yet a predictive tool that can estimate CVD risk and support the management of healthcare as well as disease prevention in terms of CVD risk among long-term colorectal cancer survivors.AimTo develop predictive tools to estimate individualized overall and each subtype of CVD risk using a nationwide cohort in South Korea.Methods and ResultsA total of 4,709 newly diagnosed patients with colorectal cancer who survived at least 5 years in the National Health Insurance System were analyzed. Cox proportional hazard regression was used for the identification of independent risk factors for the derivation of predictive nomograms, which were validated in an independent cohort (n = 3,957). Age, fasting serum glucose, γ-glutamyl transpeptidase, Charlson comorbidity index, household income, body mass index, history of chemotherapy, cigarette smoking, and alcohol consumption were identified as independent risk factors for either overall CVD or each subtype of CVD subtype. Based on the identified independent risk factors, six independent nomograms for each CVD category were developed. Validation by an independent cohort demonstrated a good calibration with a median C-index of 0.687. According to the nomogram-derived median score, relative risks of 2.643, 1.821, 4.656, 2.629, 4.248, and 5.994 were found for overall CVD, ischemic heart disease, myocardial infarction, total stroke, ischemic stroke, and hemorrhage stroke in the validation cohort.ConclusionsThe predictive tools were developed with satisfactory accuracy. The derived nomograms may support the estimation of overall and individual CVD risk for long-term colorectal cancer survivors.

Introduction Despite extensive studies on the relationship between diabetes mellitus (DM) and depression, the associations of depressive symptom severity with prevalence, awareness, treatment, and control of diabetes remain unclear. We aimed to investigate changes in these outcomes of diabetes as depressive symptoms aggravate.Research design and methods We conducted a cross-sectional analysis of 14 328 participants in the 2011–2016 National Health and Nutrition Examination Survey. Participants were classified into depressive symptom groups of none, mild, moderate, moderately severe, and severe depending on their Patient Health Questionnaire-9 scores. Multivariate logistic regression analyses were conducted in three models adjusted for expanding confounders to evaluate the associations between severity of depressive symptoms and prevalence, awareness, treatment, and control of DM.Results As depressive symptom severity worsened, both prevalence and awareness of DM increased regardless of models (p value for trend

Purpose The introduction of community-based medical education would help improve the quality of primary care. This paper suggests learning objectives and an educational program for community-based medical education. Methods The educational program was developed in a 1-day consensus workshop. Twenty experts, including faculty members from family medicine department of a college of medicine in Seoul and community-based preceptors, participated in the program. A needs-assessment survey was conducted among community-based preceptors before the workshop. Through this workshop, we derived learning objectives and a standardized curriculum for community-based medical education. Results In the questionnaire before the workshop, community-based preceptors voiced concerns over the program’s potential costs and the time required for teaching. The learning objectives and educational programs derived from the workshop’s consensus were consistent with the characteristics of the primary care. Based on the results of this workshop, the joint expert team developed a standard educational program on two core topics: clinical teaching and mentoring. Conclusion From this curriculum development process, participants could construct a more standardized curriculum for community-based medical education. Future studies are needed to evaluate the long-term outcomes of these educational programs, such as the learners’ satisfaction and achievement.

Background: Physical activity (PA), especially outdoor PA, may have twofold effects on diabetes risk: the health benefits of PA and the potential detrimental effects caused by augmented exposure to air pollution. We examined the association of combined effects of PA and air pollution with diabetes in older adults. Methods: The study participants consisted of 1,259,871 older adults aged 58 years or more from the Korean National Health Insurance Service database. The exposure to air pollution was estimated by the average ambient levels of particulate matter (PM) of the participants’ residence area. Cox proportional hazards models were used to evaluate the adjusted hazard ratios and 95% confidence intervals of developing diabetes according to the combined effect of moderate to vigorous physical activity (MVPA) and air pollution exposure. Results: Engaging in 5 or more times of MVPA/week was associated with decreased risk of diabetes within groups with both high and low/moderate levels of exposure to PM10 (low/moderate PM10 aHR 0.91, 95% CI 0.89–0.93; high PM10 aHR 0.97, 95% CI 0.94–0.99) or PM2.5 (low/moderate PM2.5 aHR 0.88, 95% CI 0.85–0.90; high PM10 aHR 0.95, 95% CI 0.91–0.99) exposure. The risk-reducing effects upon MVPA tended to be slightly attenuated, which showed the reverse J-shaped association, but still significant, among those who were exposed to a high level of air pollution. The association was consistent among stratified analyses according to the possible confounders. Conclusion: MVPA may be inversely associated with the risk of diabetes development within groups with both high and low/moderate levels of exposure to PM10 or PM2.5 in older adults. Future studies are necessary to validate whether the positive health effects of MVPA outweigh the potential detrimental effects due to augmented exposure to air pollution during MVPA.

Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength), although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests). However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

Abstract Background The effect of change in blood glucose levels on the risk of cardiovascular disease among individuals without diabetes is currently unclear. We aimed to examine the association of change in fasting serum glucose with incident cardiovascular disease and all-cause mortality among representative large population. Methods We analyzed the data from retrospective cohort of Korean National Health Insurance Service. In total, 260,487 Korean adults aged over 40 years, without diabetes mellitus and cardiovascular disease at baseline measured change in fasting serum glucose according to the criteria of impaired and diabetic fasting glucose status: normal fasting glucose (NFG, fasting glucose:

[This corrects the article DOI: 10.1371/journal.pone.0196030.].

Background Anemia is considered to increase the risk of mortality in high‐risk populations, but its effect has not been examined among young populations. This study aimed to determine the effect of hemoglobin (Hb) concentration and its changes on the risk of acute myocardial infarction (AMI), stroke, cerebrovascular disease and all‐cause mortality among young women. Methods and Results We analyzed data from the Korean National Health Information Database on 808 143 women aged 20 to 39 years without any cardiocerebrovascular disease. A 1‐time Hb concentration and changes in Hb over a 2‐year period were calculated as exposures. Participants were followed for a median of 10 years to determine the risk of AMI, stroke, cerebrovascular disease, and all‐cause mortality. There were U‐ or J‐shaped associations between Hb concentration or change in Hb and AMI, stroke, cerebrovascular disease, and all‐cause mortality. Increasing the Hb concentration from normal to high increased the risk for AMI (hazard ratio [95% confidence interval]: 1.49 [1.08‐2.04]). With regard to the risk for stroke, increasing the Hb concentration from a normal to a high range increased the risk (hazard ratio [95% confidence interval]: 1.10 [1.02‐1.35]), and decreasing the Hb concentration from a high to a normal range decreased this risk (hazard ratio [95% confidence interval]: 0.80 [0.60‐0.97]). Improving anemia to the normal Hb range decreased all‐cause mortality (hazard ratio [95% confidence interval]: 0.81 [0.69‐0.94]); however, overcorrection of Hb concentration (Hb≥14.0 g/dL) was not significant. Conclusions These findings suggest that regular Hb analysis may assist in identifying young women who are at risk of AMI, stroke, cerebrovascular disease, and all‐cause mortality.

Background Although high serum cholesterol in young adults is known to be a predictor for cardiovascular events, there is not enough evidence for the association of cholesterol level change with cardiovascular disease (CVD). This study aimed to evaluate whether the change in cholesterol is associated with incidence of CVD among young adults. Methods and Results We examined 2 682 045 young adults (aged 20–39 years) who had undergone 2 consecutive national health check‐ups provided by Korean National Health Insurance Service between 2002 and 2005. Cholesterol levels were classified into low (

# Background In this study, we aim to analyze the association between different types of cohabitation status and obstetric outcomes of preterm births (PTB), low birthweight (LBW), small for gestational age (SGA) and achieve a manifestation of social marginalization among varied marital status of women in South Korea. # Methods The study compared the birth outcomes of legally unmarried women with record of cohabitation (cohabited single), legally unmarried women with no record of cohabitation (non-cohabited single), legally married women and explored factors affecting birth outcomes of women in South Korea. A total of 790 842 singletons from married and 7788 singletons from unmarried women were examined based on the National Birth Registration Database of 2014-2015. Adjusted proportions for the occurrence of preterm births, low birth weight, and SGA were calculated and subgroup analyses were performed according to various factors like maternal age, parity, area of birth and maternal education. # Results Adjusted proportions of PTB (7.1%; 95% confidence interval (CI)=6.3-8.0, *P*-trend \

BackgroundAnemia is thought to increase mortality risks, but the effects of high hemoglobin concentration on survival are unclear. The effect of change in hemoglobin concentrations on survival in the general population is also unknown. This study aimed to examine the effect of hemoglobin concentrations and their changes on cardiovascular and all‐cause mortality risks. Methods and ResultsWe retrospectively analyzed a cohort from the NHIS‐HEALS (National Health Insurance Service–National Health Screening Cohort) database, including 170 078 men and 122 116 women without cardiovascular diseases, aged >40 years at baseline, with hemoglobin concentrations available for both first and second health examinations. We assessed 2 independent variables: “One‐time” hemoglobin concentrations and changes in hemoglobin from first to second examination. Participants were followed up for a median of 8 years to determine mortality related to myocardial infarction, stroke, all cardiovascular diseases, and all causes. Hemoglobin concentrations showed a U‐ or J‐shaped association with cardiovascular and all‐cause mortality after adjusting for cardiovascular risk factors. When anemic men achieved normal hemoglobin concentrations, the all‐cause mortality risk decreased, with an adjusted hazard ratio of 0.67 (95% confidence interval, 0.59–0.77), in comparison with those whose anemia persisted. Both increases and decreases of hemoglobin concentration outside the normal range elevated all‐cause mortality risk (adjusted hazard ratio: 1.39 [95% confidence interval, 1.28–1.49] and 1.10 [95% confidence interval, 1.01–1.20], respectively), compared with persistent normal hemoglobin concentrations. The trend was similar in women but was less significant. ConclusionsLow or high hemoglobin concentrations were associated with elevated cardiovascular and all‐cause mortality. Reaching and maintaining hemoglobin concentrations within the normal range correlated with decreased all‐cause mortality.

BACKGROUND:Hypercholesterolemia is a well-established risk factor for coronary heart disease, but the association between cholesterol level change and mortality is not fully understood. We aimed to investigate the association of 2 year (2002-2003 to 2004-2005) change in cholesterol with all-cause and cause-specific mortality in a population-based cohort study. METHODS AND FINDINGS:The study population consisted of 269,391 participants aged more than 40 years who were free of myocardial infarction, stroke and cancer using the Korean National Health Insurance Service-National Health Screening Cohort. Cholesterol levels were classified into 1st, 2nd and 3rd tertiles during each of the first and second health examinations, respectively. The participants were followed-up for all-cause and cause-specific mortality from 1 January 2006 to 31 December 2013. Compared to participants who stayed within the 2nd tertile group for cholesterol during both the first and second examinations, participants who became or maintained cholesterol levels to the 1st tertile during the second examination had increased risk of all-cause mortality [adjusted hazard ratio (aHR) with 95% confidence interval (95% CI) = 1.28 (1.18-1.38) in 1st/1st, 1.16 (1.07-1.26) in 2nd/1st and 1.47 (1.32-1.64) in 3rd/1st tertile levels, respectively]. In addition, increased or persistent high cholesterol levels to the 3rd tertile was associated with elevated risk for all-cause mortality [aHR (95% CI) = 1.10 (1.01-1.20) in 1st/2nd, 1.16(1.03-1.31) in 1st/3rd and 1.15(1.05-1.25) in 3rd/3rd tertile levels]. CONCLUSIONS:Changes in cholesterol levels in either direction to low cholesterol or persistently low cholesterol levels were associated with higher risk of mortality. Particularly, spontaneous decline in cholesterol levels may be a marker for worsening health conditions.

In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.

Background: Chronic diseases are a significant burden on the healthcare system. Nutrition counseling plays a pivotal role in the management and prevention of chronic diseases. Despite its importance, primary healthcare clinicians face practical challenges in providing effective nutritional guidance owing to time limitations, lack of information, and resistance of patients. Current Concepts: This review identifies the main barriers to nutrition counseling that are encountered by primary healthcare clinicians. We propose general strategies to overcome these obstacles, emphasizing the need for simple and easy approaches in clinical settings. In addition, specific one-point counseling methods according to gender and age that can be applied in various situations, techniques related to behavior change for motivating and guiding patients, and practical tips to cope with common conditions such as diabetes, hypertension, and obesity are also discussed. Additionally, utilization of education materials, apps, and websites as convenient resources for patients is highlighted. Discussion and Conclusion: Real-life cases demonstrated successful application of nutrition counseling in clinical practice that benefitted both the patients and clinicians. This review suggests enhancing nutrition education in medical schools and residency programs, along with activating nutrition counseling fees to motivate and support clinicians. In conclusion, this review reaffirms the importance of nutrition counseling and stresses the need for continuous learning and practice by clinicians. In the future, nutrition counseling is envisioned as a more integrated and patient-centered approach, necessitating active engagement and adaptation by primary healthcare providers. [ABSTRACT FROM AUTHOR]