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Background: Mounting evidence indicates the importance of the interplay between skeletal muscles and lipid metabolism. Remnant cholesterol (remnant-C) is considered one of the principal residual risk factors for cardiovascular disease and metabolic disorders; however, there are limited studies on the impact of remnant-C on sarcopenia., Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 were used in this nationwide population-based study. In total, 17,408 participants were enrolled in this study. The subjects were categorized into four groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry., Results: A total of 1,791 participants (10.3%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.2%; Q2, 8.7%; Q3, 11.5%; Q4, 15.7%). In the full adjusted model, those in the highest remnant-C quartile group showed significantly increased odds ratio (OR) for low muscle mass compared with those in the lowest remnant-C group after adjusting for various confounding factors (OR = 1.33, 95% confidence interval (CI) = 1.06-1.68, P < 0.05). A wide range of subgroups and sensitivity analyses showed consistent results, supporting the robustness of our findings., Conclusions: Increased remnant-C value was associated with a high risk of low muscle mass in the Korean population. Remnant-C may be a novel marker for the prediction and management of sarcopenia in aging societies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jang, Hwang, Jang, Kim, Yu, Kim, Yoo, Kim, Baik and Choi.)

Backgruound: To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea., Methods: We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus., Results: The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage., Conclusion: DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Radioactive 131 I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service's National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD ( International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4-5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2-12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370-630 MBq) in the RAI therapy group. During 2004-2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88-1.06); this remained at 0.96 (95% CI, 0.83-1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17-4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66-1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Backgruound: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD., Methods: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study., Results: Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users., Conclusion: The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Agastache rugosa, also known as Korean mint, is a perennial plant from the Lamiaceae family that is traditionally used for various ailments and contains antioxidant and antibacterial phenolic compounds. Molecular breeding of A. rugosa can enhance secondary metabolite production and improve agricultural traits, but progress in this field has been delayed due to the lack of chromosome-scale genome information. Herein, we constructed a chromosome-level reference genome using Nanopore sequencing and Hi-C technology, resulting in a final genome assembly with a scaffold N50 of 52.15 Mbp and a total size of 410.67 Mbp. Nine pseudochromosomes accounted for 89.1% of the predicted genome. The BUSCO analysis indicated a high level of completeness in the assembly. Repeat annotation revealed 561,061 repeat elements, accounting for 61.65% of the genome, with Copia and Gypsy long terminal repeats being the most abundant. A total of 26,430 protein-coding genes were predicted, with an average length of 1,184 bp. The availability of this chromosome-scale genome will advance our understanding of A. rugosa's genetic makeup and its potential applications in various industries., (© 2023. The Author(s).)

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Background: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus., Methods: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed., Results: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy., Conclusion: Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Background: This study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to critical coronavirus disease 2019 (COVID-19)., Methods: We analyzed 4069 COVID-19 patients between January and June 2020 in South Korea, classified into four groups according to metabolic health status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The primary outcome was a composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), extracorporeal membrane oxygenation (ECMO), and death. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for the outcome., Results: The incidence rate (per 100 person-months) of critical COVID-19 was the lowest in the MHNW group (0.90), followed by the MHO (1.64), MUNW (3.37), and MUO (3.37) groups. Compared with MHNW, a significantly increased risk of critical COVID-19 was observed in MUNW (HR, 1.41; 95% CI, 1.01-1.98) and MUO (HR, 1.77; 95% CI, 1.39-2.44) but not in MHO (HR, 1.48; 95% CI, 0.98-2.23). The risk of ICU admission or IMV/ECMO was increased only in MUO; however, the risk of death was significantly higher in MUNW and MUO. The risk of critical COVID-19 increased insignificantly by 2% per 1 kg/m 2 BMI increase but significantly by 13% per 1 metabolically unhealthy component increase, even after mutually adjusting for BMI and metabolic health status., Conclusions: Metabolic health is more important to COVID-19 outcomes than obesity itself, suggesting that metabolic health status should be considered for a precise and tailored management of COVID-19 patients., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest relevant to this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Diabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes., Methods: We included 152,931 individuals without diabetes from the Korean National Health Insurance Service-Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM)., Results: A total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan-Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07-1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income., Conclusions: Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes., (© 2022. The Author(s).)

Atopic dermatitis (AD) has been increasing worldwide over the past few decades. AD has been reported to be associated with an increased risk of osteoporosis and fractures in adult AD patients. The aim of this study was to investigate the bone mineral density (BMD) to evaluate osteoporosis risk in young adults with AD by sex. This was a case-control cohort study using a national dataset from the Korea National Health and Nutrition Examination Survey 2007-2009. We included young adult AD patients (men aged 19 ≤ and < 50 years, premenopausal women aged 19 ≤ and < 50 years) and 1:5 propensity score weighting controls by age, sex, body mass index (BMI), vitamin D level, and alcohol/smoking status. BMD was measured by double energy X-ray absorptiometry at the lumbar spine, femur neck, and total femur. The prevalence of low BMD, defined by a Z-score ≤  - 2.0, was compared between AD and without AD. We analyzed 311 (weighted n = 817,014) AD patients and 8,972 (weighted n = 20,880,643) controls. BMD at the lumbar spine was significantly lower in the male AD group than in the male control group (mean ± SE, 0.954 ± 0.016 vs. 0.989 ± 0.002, P = 0.03). The prevalence of low BMD (Z-score) did not significantly differ between AD and non-AD subjects in both men (3.8% vs. 2.7%, P = 0.56) and women (6.4% vs. 3.3%, P = 0.40). Among AD patients, early age at diagnosis of AD, longer duration of AD, lower BMI, rural residence (for men), less education, low vitamin D level, late menarche, and more pregnancies (for women) were associated with low BMD. In conclusion, low BMD did not occur more frequently in young adults with AD than in non-AD controls. However, early-onset/longer AD duration and lower BMI were associated with low BMD among young adult patients with AD., (© 2021. The Author(s).)

The prevalence of young-onset (diagnosis at age < 40 years) type 2 diabetes mellitus (T2DM) is increasing globally. Young-onset T2DM has a common pathophysiology of glucose dysregulation as in late-onset T2DM. However, it presents a greater association with obesity and a more rapid decline in β-cell function than late-onset T2DM. Accumulating evidence indicates that disease progression in young-onset T2DM is rapid, resulting in early and frequent development of microvascular and macrovascular complications, as well as premature death. Improper management and low adherence to medical therapy are important issues in young-onset T2DM. This review discusses the epidemiology, disease entity, and clinical issues associated with young-onset T2DM. We also present the prevalence and clinical characteristics of patients with young-onset T2DM in South Korea.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Background: The global incidence of NAFLD is rising sharply due to various risk factors. As previous studies reported adverse health impact of long working hours on metabolic diseases, such as diabetes mellitus and obesity, it is plausible that NAFLD is also associated with working excessive hours. However, data regarding this issue is limited., Methods: In this cross-sectional study based on Korea National Health and Nutrition Examination Survey VII, 5,661 working adults without previous liver disease or heavy alcohol drinking habits were included. The subjects were categorized into three groups according to working hours: 36-42, 43-52, and 53-83 hours/week. NAFLD was defined using the hepatic steatosis index (HSI), which is a validated prediction model for determining NAFLD., Results: The prevalence of NAFLD (HSI ≥36) increased with longer working hours: 23.0%, 25.6%, and 30.6% in the 36-42, 43-52, and 53-83 hours/week group, respectively (p <0.001). Subjects who worked 53-83 hours/week had higher odds for NAFLD than those who worked the standard 36-42 hours/week (OR 1.23, 95% CI 1.02-1.50, p = 0.033) after adjusting for age, sex, body mass index, smoking, alcohol, exercise, diabetes mellitus, hypertension, serum triglyceride, and total cholesterol. This association was consistent across subgroups according to working schedule (daytime vs. shift workers) or occupation type (office vs. manual workers). In particular, the relationship between long working hours and NAFLD was pronounced in workers aged <60 years and in female workers., Conclusions: Long working hours was significantly associated with NAFLD. Further prospective studies are required to validate this finding with causal relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer [HSC] declared a past co-authorship with one of the authors [KMC] to the handling editor., (Copyright © 2021 Song, Kim, Roh, Yu, Kim, Yoo, Seo, Kim, Kim, Baik and Choi.)

Background: Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients., Methods: We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes., Results: Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events., Conclusion: RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.

The triglyceride-glucose (TyG) index is a simple surrogate marker of insulin resistance. We evaluated the association of the TyG index with low muscle mass using a nationwide population-based representative data. This is a cross-sectional study that included 9477 participants aged ≥ 40 years from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. The TyG index was calculated as ln[triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Dual-energy X-ray absorptiometry was used to measure appendicular lean mass (ALM). Low muscle mass was defined an ALM/weight of 2 standard deviations (SD) below of young participants. The overall prevalence of low muscle mass was 4.7%. The prevalence of low muscle mass increased linearly with the quartiles of the TyG index, 2.5%, 4.2%, 5.6%, and 6.7% in Q1-Q4, respectively. The TyG index was negatively associated with ALM/weight both in men (r = - 0.302) and women (r = - 0.230). The odds ratio (OR) for low muscle mass was 2.08 in the highest quartile compared to the lowest quartile. High TyG index was associated with an increased risk of low muscle mass (OR for 1SD increase: 1.13). Increased TyG index was associated with the risk of low muscle mass independent of confounding factors.

Background: Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations. We investigated whether variability in long-term fasting plasma glucose (FG) can predict the development of stroke, myocardial infarction (MI), and all-cause mortality in patients with diabetes., Methods: This is a retrospective cohort study using the data provided by the Korean National Health Insurance Corporation. A total of 624,237 Koreans ≥ 20 years old with diabetes who had undergone health examinations at least twice from 2005 to 2008 and simultaneously more than once from 2009 to 2010 (baseline) without previous histories of stroke or MI. As a parameter of variability of FG, variability independent of mean (VIM) was calculated using FG levels measured at least three times during the 5 years until the baseline. Study endpoints were incident stroke, MI, and all-cause mortality through December 31, 2017., Results: During follow-up, 25,038 cases of stroke, 15,832 cases of MI, and 44,716 deaths were identified. As the quartile of FG VIM increased, the risk of clinical outcomes serially increased after adjustment for confounding factors including duration and medications of diabetes and the mean FG. Adjusted hazard ratios (95% confidence intervals) of FG VIM quartile 4 compared with quartile 1 were 1.20 (1.16-1.24), 1.20 (1.15-1.25), and 1.32 (1.29-1.36) for stroke, MI and all-cause mortality, respectively. The impact of FG variability was higher in the elderly and those with a longer duration of diabetes and lower FG levels., Conclusions: In diabetes, long-term glucose variability showed a dose-response relationship with the risk of stroke, MI, and all-cause mortality in this nationwide observational study.

The aim of this study is to investigate whether GGT variability is able to predict the risk of end-stage renal disease (ESRD). The study subjects were Koreans who conducted health exams supported by the Korean National Health Insurance Corporation during 2009-2012 (baseline). After excluding individuals aged < 40 years, heavy alcoholics, or those with histories of chronic liver disease or ESRD, we followed 6,058,995 individuals. We calculated the average successive variability (ASV) of GGT values during the 5 years before the baseline as a parameter of variability. Using Cox proportional analyses, we evaluated the risk of ESRD according to GGT ASV quartiles, defined as the initiation of renal replacement therapy or kidney transplantation, or December 31, 2016. During 38,663,279.3 person-years of follow-up, 12,057 cases of ESRD were identified. Compared with GGT ASV quartile 1, the risk of ESRD was higher in ASV quartiles 3-4 and increased serially, even after adjustment for several metabolic parameters, baseline renal function, presence of comorbidities, low income, and baseline GGT and hemoglobin level. The fully adjusted hazard ratios (95% confidence intervals) of GGT ASV quartiles 3 and 4 were 1.06 (1.01-1.12) and 1.12 (1.06-1.18), respectively. In conclusion, GGT variability is a putative risk factor for ESRD in Koreans.

Objective: Gamma-glutamyl transferase (GGT) is associated with oxidative stress, inflammation, cardiovascular disease and mortality. Variability in metabolic parameters has recently emerged as an indicator of adverse health outcomes, including heart failure (HF)., Methods: We investigated whether GGT variability was associated with the incidence of hospitalisation for heart failure (HHF) in a Korean population without previous HF, ischaemic heart disease or liver disease. This longitudinal cohort study analysed 119 201 individuals from the Korean National Health Insurance Service-National Health Screening Cohort. GGT variability was calculated as the coefficient of variation (CV), SD and variability independent of the mean (VIM)., Results: During the 8.4 years of follow-up, 1387 cases of HHF (1.16%) developed. In the multivariable-adjusted model, the HR of HHF was 1.22 (95% CI 1.05 to 1.42) in the highest quartile of GGT variability compared with the lowest quartile, as assessed by CV after adjusting for confounding factors, including alcohol consumption and mean GGT levels. Consistent results were obtained using other indices of GGT variability such as SD (HR 1.37, 95% CI 1.16 to 1.62) and VIM (HR 1.29, 95% CI 1.11 to 1.50). In a subgroup analysis stratified by risk factor variables, although a similar relationship was observed, it was more prominent in individuals with dyslipidaemia., Conclusions: The results of the present study demonstrated that variability in GGT was independently associated with the incidence of HHF. These findings suggest that higher GGT variability may be useful as an indicator of future risk of HF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the prevalence of osteoporosis among North Korean women refugees when compared with South Korean women, who have identical genetic backgrounds but experience different environments., Design: Comparative cross-sectional study., Setting: North Korean Refugee Health in South Korea (NORNS) study in South Korea., Participants: We evaluated 122 North Korean women who participated in NORNS study and 366 age-matched/menopausal status-matched South Korean women from the Korea University Medical Center (KUMC) health examination cohort. The median age of the NORNS participants was 46 years (IQR, 40-60 years) with 52 women (42.6%) being postmenopausal., Results: Among the postmenopausal women, NORNS participants had a higher body mass index and number of pregnancies and lower physical activity than the KUMC participants. The overall prevalence of osteoporosis was 48% (25/52) and 17% (27/156) in NORNS and KUMC participants, respectively. The bone mineral density (BMD) values at the lumbar spine, femur neck and total hip were significantly lower in postmenopausal NORNS women than in the postmenopausal KUMC women. Old age, low body weight and late age of menarche were associated with low BMD among the postmenopausal North Korean refugees. In premenopausal participants, the NORNS women had lower body weight and physical activity than the KUMC women at baseline. All the NORNS women had normal Z-scores, although the BMD at the lumbar spine was significantly lower in NORNS women than in the KUMC women (0.952 vs 1.002 g/cm 2 , p<0.001)., Conclusions: Osteoporosis is a prevalent health problem in postmenopausal North Korean women refugees living in South Korea. It is conceivable to prepare vigilant countermeasures for bone health deterioration in this growing population, especially for postmenopausal women. Further research is warranted to determine the cause of the differences between participants of the same ethnic group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent growing evidences suggest that body weight (Bwt) variability, a repeated loss and regain of weight within a specific period, causes metabolic disturbances and can be a marker for poor homeostasis. Although there have been many studies about the association between Bwt variability and various health status, its association with the incidence of dementia among elderly people has not been examined. Methods: We performed a retrospective elderly cohort study from 19,987 participants with mean age 73 years old in the Korean National Health Insurance Service. We examined the risk of incident dementia, including Alzheimer's dementia and vascular dementia, according to the quartile of Bwt variability, represented as coefficient of variation (Bwt-CV), SD (Bwt-SD), and variability independent of the mean (Bwt-VIM). Results: In fully adjusted model, the group with the highest Bwt variability (Bwt-VIM Q4) showed an increased risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.206-1.603) and Alzheimer's dementia (HR 1.46, CI 1.240-1.724) compared to the lowest quartile (Bwt-VIM Q1). We also found that subjects with the highest Bwt variability (Q4) and underweight BMI had a significantly increased risk of developing dementia (HR 1.994, 95% CI 1.302-3.054), while subjects with low Bwt variability (Q1 and Q2) and obese BMI had decreased risk of dementia (HR 0.664, 95% CI 0.505-0.872 and HR 0.648, 95% CI 0.493-0.852, respectively) compared to reference group (lowest Bwt variability (Q1) with normal baseline BMI). The effect of Bwt variability on the incidence of dementia was more prominent in subjects <75 years old and abnormal BMI groups (P for interaction < 0.05). Conclusion: The present study revealed that high Bwt variability was associated with an increased risk of dementia in the elderly., (Copyright © 2020 Roh, Hwang, Kim, Lee, Hong, Kim, Seo, Kim, Kim, Choi, Baik and Yoo.)

Fibrates, peroxisome proliferator-activated receptor-α agonists, are potent lipid-modifying drugs. Their main effects are reduction of triglycerides and increase in high-density lipoprotein levels. Several randomized controlled trials have not demonstrated their benefits on cardiovascular risk reduction, especially as an "add on" to statin therapy. However, subsequent analyses by major clinical trials, meta-analyses, and real-world evidence have proposed their potential in specific patient populations with atherogenic dyslipidemia and metabolic syndrome. Here, we have reviewed and discussed the accumulated data on fibrates to understand their current status in cardiovascular risk management., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Diabetes Association.)

Objectives: Although it has been well-established that menopause causes a shift in body fat, there has been no study conducted yet to examine the best obesity parameters to predict the risk of nonalcoholic fatty liver disease (NAFLD) in this population. Thus, the aim of this study was to clarify the superiority among various obesity indices such as body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting NAFLD in pre- and postmenopausal women., Methods: This cross-sectional analysis included 620 healthy women (318 premenopausal and 302 postmenopausal women) between 20 and 80 years of age recruited from the Health Promotion Center of Korea University Guro Hospital. NAFLD was diagnosed by abdominal ultrasonography., Results: In premenopausal women, there were no statistical differences in the area under the curve values among the three obesity indices, whereas, in postmenopausal women, the area under the curve value of WHR was significantly larger than those of either BMI (difference between area: 0.102, 95% confidence interval: 0.031, 0.173) or WC (difference between area: 0.064, 95% confidence interval: 0.018-0.109). Furthermore, in postmenopausal women, the combination of WHR with BMI or WC significantly increased predictive power of NAFLD when compared to using BMI or WC alone. The optimal cutoff values for BMI, WC, and WHR for detecting NAFLD were 23.9 kg/m, 69 cm, and 0.81 in premenopausal women and 22.9 kg/m, 74 cm, and 0.86 in postmenopausal women, respectively., Conclusions: In premenopausal women, BMI, WC, and WHR hold similar potential in predicting the risk of NAFLD, whereas, in postmenopausal women, WHR is the most useful discriminative indicator for NAFLD. Women's optimal cutoff values for NAFLD were different according to menopausal status.

Background: Long-term variability of cardiometabolic risk factors have been suggested as the risk factors for cardiovascular disease and mortality. However, the effect of long-term variability of total cholesterol (TC) on incident atrial fibrillation (AF) has not been examined., Methods and Findings: We explored whether visit-to-visit TC variability are associated with the risk of incident AF in 160,165 Korean adults, using the population-based Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) database, over a median duration of 8.4 years. TC variability was measured as coefficients of variance (TC-CV), standard deviation (TC-SD), and variability independent of the mean (TC-VIM). Kaplan-Meier analysis demonstrated a decreased disease-free probability in the highest quartile group of TC variability compared to that in the other groups. In the multivariate Cox proportional hazard analysis, the risk of AF increased significantly in the highest quartile group of TC variability. After multivariate adjustment for confounding variables including mean TC levels, the hazard ratio for incident AF was 1.15 (95% confidence interval 1.05-1.25; P = 0.0035) when comparing the highest with the lowest TC variability quartile (TC-CV). These relationships were consistent with TC variability defined using TC-SD or TC-VIM. Subgroup analyses, including age, sex, body mass index, and cardiometabolic disorders, showed similar results., Conclusions: The present study is the first to demonstrate that high TC variability was associated with an increased risk of AF., Competing Interests: The authors have declared that no competing interests exist.

Background: To determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort., Methods: From a nationwide cohort in Korea (2008-2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models., Results: During a median follow-up of 19.6 months (interquartile range 7.2-36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81-1.23), IS (HR, 0.95; 95% CI 0.74-1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46-1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41-3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07-2.04)., Conclusions: This real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.

Objective: Although increasing evidence suggests the association between short-term variability of fasting plasma glucose (FPG) and diabetic complications or mortality, the impact of visit-to-visit variability of FPG on the development of type 2 diabetes (T2D) has not been evaluated., Research Design and Methods: Our analysis included 131,744 Korean men and women without diabetes using the Korean National Health Insurance System cohort with periodic health examination program. FPG variability was calculated using the coefficient of variation (FPG-CV), SD (FPG-SD), and variability independent of the mean (FPG-VIM)., Results: During the median follow-up time of 8.3 years, Kaplan-Meier curves demonstrated lower disease-free probability in the higher FPG variability group compared with the lower FPG variability group. Multivariable Cox proportional hazards analysis exhibited that the hazard ratio for incident T2D was 1.67 (95% CI 1.58-1.77, P < 0.001) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for confounding variables, including mean FPG. The association between FPG variability and the risk of T2D was consistent when modeling using FPG-SD and FPG-VIM in both normal and impaired fasting glucose groups. A 1 SD increase in the FPG-CV was associated with a 24% increased risk of T2D in the fully adjusted model., Conclusions: Increased variability of FPG is associated with the development of T2D independently of diverse risk factors., (© 2018 by the American Diabetes Association.)

This study investigated the effects of diabetes and antidiabetic medications on the risk of pancreatic cancer(PaC). We extracted data on Koreans with newly diagnosed diabetes and selected age- and sex-matched controls provided by the National Health Insurance Corporation. Incident PaC was defined as a new registration in the Korea Central Cancer Registry under ICD-10 C25 with admission history until 2015. During 19,429,617.1 person-years, 8,589 PaCs were identified in 1,005,409 subjects for diabetes group and 4,021,636 subjects for control group. The diabetes group showed more than a two-fold risk for PaC compared with the control group. Among antidiabetic medications, metformin, thiazolidinedione, and dipeptidyl peptidase-4 inhibitor exposure was associated with decreased risk for future PaC(hazard ratio[95% confidence interval] = 0.86[0.77-0.96], 0.82[0.68-0.98], 0.57[0.51-0.64], respectively), whereas sulfonylurea and insulin exposure was related to increased risk(hazard ratio[95% CI] = 1.73[1.57-1.91], 2.86[1.43-5.74], respectively) compared to subjects with no drug exposure. Moreover, subjects with dual exposure history to metformin plus thiazolidinedione or metformin plus dipeptidyl peptidase-4 inhibitor had a lower risk of PaC compared to metformin-only treated subjects. In conclusion, Korean adults with diabetes are at higher risk of PaC compared with nondiabetic individuals, and this risk may be modified by antidiabetic medications.

Although liver enzymes, such as γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.

Aim: The aim of the present study was to evaluate the age-specific prevalence of dementia, and develop a metabolic risk indicator for dementia according to sex., Methods: This cross-sectional study was carried out from September 2007 through December 2012 with 19 935 elderly participants in metropolitan Seoul, Korea. Multiphase assessments were used to measure metabolic risk factors and confirm dementia according to sex. Specifically, multivariate logistic regression analyses were used to identify how elderly men and women differed in regard to metabolic risk indicators of dementia., Results: The adjusted prevalence rates of dementia in elderly Seoul residents were estimated at 4.9%, 6.1% and 5.6% in men, women and the overall population, respectively. Stroke conferred an odds ratio of 5.14 (95% CI 3.91-6.77) and 2.55 (95% CI 2.01-3.25) in men and women, respectively. Additionally, within the female population, diabetes mellitus conferred an odds ratio of 1.29 (95% CI 1.09-1.53), whereas alcohol consumption conferred an odds ratio of 0.77 (95% CI 0.61-0.97)., Conclusions: Stroke played a primary role as a metabolic risk indicator of dementia in elderly men, while diabetes mellitus and alcohol abstinence were important metabolic risk factors in elderly women. Taken together, the data show that when designing preventative measures against dementia based on metabolic risk, sex needs to be taken into account. Geriatr Gerontol Int 2017; 17: 2136-2142., (© 2017 Japan Geriatrics Society.)

Objectives: To determine the prevalence of metabolic syndrome (MetS) and its related factors among North Korean refugees (NKR) in South Korea., Design: Cross-sectional study conducted using a questionnaire and anthropometric and biochemical data on NKR in South Korea., Setting: Seoul, South Korea., Participants: A sample of NKR who voluntarily underwent medical examinations in Anam Hospital of Korea University, Seoul, South Korea (N=708, consisting of 161 males and 547 females). To compare the prevalence of MetS, 1416 age- and gender-matched individuals from the South Korean population (SKP, at a ratio of 1:2 to NKR) were randomly selected from the fifth Korean National Health and Nutrition Examination Survey., Main Outcome Measures: The prevalence of MetS and its related factors among NKR in South Korea and comparison with its prevalence among the general SKP., Results: The prevalence of MetS among male and female NKR in South Korea was 19.7% and 17.2%, respectively. Although obesity is more prevalent in South than in North Korea, we found no difference in the prevalence of MetS between the female NKR and SKP groups (17.2% vs 16.6%, respectively; p=0.830). As regards the males, the small sample size of the NKR group yielded insufficient evidence of any difference in MetS prevalence between the NKR and SKP groups (19.7% vs 26.2%, respectively; p=0.134). We found that excess weight gain (≥5%) in South Korea was significantly associated with MetS among NKR., Conclusions: The prevalence of MetS among NKR did not differ from that in the SKP group despite the lower prevalence of obesity in NKR than in the general SKP. The fact that excess weight gain in South Korea was associated with the risk of MetS suggests that public health policy makers should focus on preventing excess weight gain in NKR during resettlement in South Korea., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Vitamin D deficiency is now recognised as a common health problem associated with various chronic diseases; however, it has not been fully elucidated among the minority groups. Here, we aimed to investigate the prevalence of vitamin D deficiency and its associated metabolic risk factors among North Korean refugees living in South Korea., Design: Cross-sectional analysis from the longitudinal cohort, the North Korean refugee health in South Korea (NORNS) study., Participants: A total of 386 North Korean refugees aged ≥30 years, who measured serum 25-hydroxy vitamin D (25(OH)D) level., Results: The prevalence of vitamin D deficiency (25(OH)D <20 ng/mL) was 87% and no participants had an adequate vitamin D level (25(OH)D ≥30 ng/mL). Underweight participants (body mass index (BMI) <18 kg/m(2)) had significantly lower 25(OH)D levels than individuals with normal BMI (≥18.5 and<23 kg/m(2)). In the multivariate logistic regression analysis, the lowest 25(OH)D level (<10 ng/mL) was significantly associated with metabolic syndrome (OR, 6.37, 95% CI 1.34 to 30.3), high triglyceride (OR, 6.71, 95% CI 1.75 to 25.7), and low high-density lipoprotein (OR, 5.98, 95% CI 1.54 to 23.2) compared with 25(OH)D levels ≥20 ng/mL after adjusting for age, sex, season, length of residence in South Korea, physical activity and BMI., Conclusions: Vitamin D deficiency is very common among North Korean refugees in South Korea. Despite their lower BMI, vitamin D deficiency was associated with metabolic syndrome in this population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The association between body mass index (BMI) and mortality is not conclusive, especially in East Asian populations. Furthermore, the association has been neither supported by recent data, nor assessed after controlling for weight changes., Methods: We evaluated the relationship between BMI and all-cause or cause-specific mortality, using prospective cohort data by the National Health Insurance Service in Korea, which consisted of more than one million subjects. A total of 153,484 Korean adults over 30 years of age without pre-existing cardiovascular disease or cancer at baseline were followed-up until 2010 (mean follow-up period = 7.91 ± 0.59 years). Study subjects repeatedly measured body weight 3.99 times, on average., Results: During follow-up, 3,937 total deaths occurred; 557 deaths from cardiovascular disease, and 1,224 from cancer. In multiple-adjusted analyses, U-shaped associations were found between BMI and mortality from any cause, cardiovascular disease, and cancer after adjustment for age, sex, smoking status, alcohol consumption, physical activity, socioeconomic status, and weight change. Subjects with a BMI < 23 kg/m2 and ≥ 30 kg/m2 had higher risks of all-cause and cause-specific mortality compared with the reference group (BMI 23-24.9 kg/m2). The lowest risk of all-cause mortality was observed in subjects with a BMI of 25-26.4 kg/m2 (adjusted hazard ratio [HR] 0.86; 95% CI 0.77 to 0.97). In subgroup analyses, including the elderly and those with chronic diseases (diabetes mellitus, hypertension, and chronic kidney disease), subjects with a BMI of 25-29.9 kg/m2 (moderate obesity) had a lower risk of mortality compared with the reference. However, this association has been attenuated in younger individuals, in those with higher socioeconomic status, and those without chronic diseases., Conclusion: Moderate obesity was associated more strongly with a lower risk of mortality than with normal, underweight, and overweight groups in the general population of South Korea. This obesity paradox was prominent in not only the elderly but also individuals with chronic disease.

Background/aims: The aim of this study was to compare the survival in elderly hepatocellular carcinoma (HCC) patients treated with curative modalities (radiofrequency ablation (RFA), percutaneous ethanol injection (PEIT) and surgery) to those treated with transcatheter arterial chemoembolization (TACE) and supportive care., Methodology: Medical records of patients with HCC older than 75 years who had visited a single tertiary medical center from January 2000 to December 2011 were reviewed (n = 58). Multivariable-adjusted hazard ratios (HR) for mortality with 95% confidence intervals (CI) were estimated using Cox proportional hazard models., Results: Twenty-nine patients were treated by TACE, 19 patients by supportive care, and 10 patients by curative treatment (four by PEIT, three by surgery and three by RFA).Variables associated with increased survival were better Child-Pugh class and lower TNM stage. Treatment with curative intent showed significant survival benefit compared to TACE (HR for mortality, 0.10; 95% CI, 0.01-0.95). In a subgroup analysis among patients with resectable HCC, supportive care showed significantly worse survival over TACE (HR for mortality, 6.47; 95% CI, 2.14-19.56) and curative intent (HR for mortality, 16.23; 95% CI, 1.92-136.83)., Conclusions: Curative treatment seems to have a better survival benefit in comparison with other treatment modalities in elderly HCC patients.

Study Objectives: To determine whether short sleep duration alone or combined with obstructive sleep apnea (OSA) is associated with regional body fat including abdominal visceral fat area (VFA) among Korean adults., Design: Cross-sectional study., Setting: Ansan, South Korea., Participants: There were 838 community participants age 40-69 y from the Korean Genome and Epidemiology Study., Measurements and Results: Subjective habitual sleep duration and OSA were defined based on a structured sleep questionnaire and a home portable sleep study, respectively. Abdominal VFA and hepatic fat components were assessed by computed tomography. Adjusted mean VFA and hepatic fat were highest in the shortest sleep duration group (< 5 h) and decreased linearly with increasing sleep duration. Individuals with OSA (apnea-hypopnea index ≥ 5) had a higher body mass index, waist circumference, percent body fat, VFA, and hepatic fat than those without OSA after adjusting for age and sex. The adjusted odds ratio (OR) for visceral obesity (VFA ≥ 100 cm2) was 2.05 (95% confidence interval [CI], 1.09-3.86) in individuals sleeping less than 5 h compared with those sleeping longer than 7 h, and 1.57 (95% CI, 1.08-2.26) in individuals with OSA compared with those without OSA, after adjusting for all confounding factors including body mass index. A combination of short sleep duration (< 5 h) and OSA substantially increased the OR for visceral obesity (OR, 4.40, 95% CI, 1.80-10.77) compared with those who slept longer (≥ 7 h) without OSA., Conclusion: Short sleep duration and OSA are independently associated with visceral obesity in adults. The association is particularly strong in short sleepers with OSA.

Objectives: To examine the relationship between depression and various components of body composition, including fat and muscle, in elderly Koreans., Design: A cross-sectional sample of a longitudinal cohort from the Ansan Geriatric (AGE) Study., Setting: Elderly people living in urban area (Ansan City, South Korea)., Participants: Eight hundred thirty-six participants (378 male, 458 female) aged 60 and older were recruited from April 2006 to January 2008., Measurements: Depressive symptoms were examined using the Korean version of the 30-item Geriatric Depression Scale (KGDS). Participants taking antidepressant medications or with a KGDS score of 14 or greater were classified as having depression. Abdominal visceral fat area (VFA) and subcutaneous fat area were assessed using single-slice computed tomography, and appendicular skeletal muscle mass (ASM) and percentage body fat (%BF) were determined using whole-body dual-energy X-ray absorptiometry., Results: Elderly men with depression had a lower ASM than those without depression (P = .01) after adjusting for age, body weight, and height. In men, the risk of depression was lower with higher body mass index (BMI) (odds ratio (OR) per 1-standard deviation (SD) increase = 0.70, 95% confidence interval (CI) = 0.51-0.96) after adjusting for all confounding variables and higher ASM (OR per 1-SD increase = 0.49; 95% CI = 0.29-0.85) after controlling for age, height, and weight. Similarly, depression was negatively associated with BMI in women (OR per 1-SD increase = 0.73; 95% CI = 0.56-0.95). Waist circumference, %BF, and VFA were not consistently associated with depression in men or women., Conclusion: Depression in elderly Koreans is associated with low body mass and sarcopenia, especially in men., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)