Search

Background Substantial evidence supports an association between physical activity and cognitive function. However, the role of muscle mass and function in brain structural changes is not well known. This study investigated whether sarcopenia, defined as low muscle mass and strength, accelerates brain volume atrophy. Methods A total of 1284 participants with sarcopenic measurements and baseline and 4-year follow-up brain magnetic resonance images were recruited from the Korean Genome and Epidemiology Study. Muscle mass was represented as appendicular skeletal muscle mass divided by the body mass index. Muscle function was measured by handgrip strength. The low mass and strength groups were defined as being in the lowest quintile of each variable for one’s sex. Sarcopenia was defined as being in the lowest quintile for both muscle mass and handgrip strength. Results Of the 1284 participants, 12·6%, 10·8%, and 5·4% were classified as the low mass, low strength, and sarcopenia groups, respectively. The adjusted mean changes of gray matter (GM) volume during 4-year follow-up period were − 9·6 mL in the control group, whereas − 11·6 mL in the other three groups (P Conclusions Sarcopenia is associated with parietal GM volume atrophy, in a middle-aged population. Maintaining good levels of muscle mass could be important for brain health in later adulthood.

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P

Background: To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term dura ble glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (

Background: Recently, a few studies have reported different results regarding the relationship between metabolic health and obesity phenotype and several cancers. We examined the effects of metabolic health and obesity phenotype on pancreatic cancer using a nationwide population-based cohort database. Methods: Using the Korean National Health Insurance Service–Health Screening Cohort, we enrolled 347,434 Korean adults who underwent a health examination between 2009 and 2010 and were followed until 2015. This population was divided into four groups based on metabolically healthy status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Results: Over a median follow-up of 6.1 (5.5–6.5) years, 886 individuals were diagnosed with pancreatic cancer. The adjusted HRs for incident pancreatic cancer were 1.52 [95% confidence interval (CI) 1.27–1.81] and 1.34 (95% CI, 1.12–1.61) for the MUNW and MUO phenotypes (compared with the MHNW phenotype) after adjusting for various confounding factors. However, compared with the MHNW phenotype, the MHO phenotype did not show an elevated risk of pancreatic cancer. Moreover, the HR for pancreatic cancer gradually increased with an increase in number of metabolically unhealthy components, even after adjusting for BMI (Ptrend < 0.001). Conclusions: Regardless of BMI, metabolically unhealthy phenotype demonstrated significantly increased risk of pancreatic cancer, whereas obese individuals with metabolically healthy phenotype did not. Impact: These findings suggest that metabolically unhealthy phenotype might represent a potential risk factor for pancreatic cancer occurrence independent of obesity.

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

Aims/Introduction We investigated the risk of incident type 2 diabetes according to the cumulative exposure to obesity or metabolic syndrome (MetS) during annual or biennial health examinations. Materials and Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this retrospective longitudinal study. The risk for type 2 diabetes was analyzed according to the cumulative exposure to obesity and MetS among individuals who underwent four health examinations from 2009 to 2012 or 2013 (n = 2,851,745). Results During examinations, 28.56 and 17.86% of the total participants showed fluctuations in metabolic health state and obesity, respectively. During a mean 5.01 years of follow up, 98,950 new type 2 diabetes cases developed. The risk for type 2 diabetes increased with the increase in exposure to MetS (hazard ratio [HR] 2.92, 95% confidence interval [CI] 2.86–2.99; HR 4.96, 95% CI 4.85–5.08; HR 7.46, 95% CI 7.30–7.63; HR 12.24, 95% CI 12.00–12.49 in groups with number of exposures one to four, respectively) and obesity (HR 1.60, 95% CI 1.56–1.65; HR 1.87, 95% CI 1.81–1.92; HR 2.25, 95% CI 2.19–2.31; HR 3.46, 95% CI 3.41–3.51 in groups with number of exposures one to four, respectively), showing a more detrimental effect of cumulative exposure to MetS, when compared with the exposure to obesity. Conclusions Metabolic health and obesity fluctuated within a relatively short period of 4–5 years. Although the impact was much greater for MetS than for obesity, the cumulative duration of both obesity and MetS was associated with an increased risk of type 2 diabetes in a dose‐response manner. Therefore, continuously maintaining metabolic health and normal weight is crucial to prevent incident type 2 diabetes., In this large‐scale longitudinal study including 2,851,745 Korean adults with four annual or biennial health examinations, the metabolic health and obesity status fluctuated within a relatively short period of 4–5 years. The cumulative exposure to both metabolic syndrome and obesity was associated with an increased hazard of incident type 2 diabetes in a graded dose‐response manner, although the exposure to metabolic syndrome had a much greater impact than the exposure to obesity. Continuously maintaining metabolic health and normal weight would be warranted to prevent incident type 2 diabetes.

Objective Thyroid cancer (TC) incidence has increased robustly in Korea. However, the actual cause of death, overall mortality risk, and cause-specific mortality risk in TC patients have not been clearly elucidated. Design Retrospective cohort study. Methods We analyzed 4082 TC patients from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS, 2002–2013) with a median of 48-month follow-up. We compared these patients with 12 246 controls matched for age, sex, and histories of major cardiovascular disease (CVD) to investigate the cause of death and risks of overall and cause-specific mortality. Results Overall, 61 deaths (1.5%) occurred in the TC group. The most common cause of death was TC-specific mortality (32.8%), followed by other malignancy-related mortality (31.1%) and CVD mortality (13.1%). The overall mortality risk was comparable between the TC and control groups (unadjusted hazard ratio (HR): 1.17; 95% confidence interval (CI): 0.87–1.58); the adjusted HR remained at 1.25 (95% CI: 0.90–1.74) after multivariate adjustment for body mass index (BMI), socioeconomic status (SES), smoking, alcohol consumption, and histories of hypertension, diabetes mellitus, and dyslipidemia. In addition, there was not enough evidence against the surmise that the CVD mortality risk was similar between the TC and control groups, with an HR of 0.50 (95% CI: 0.22–1.16) after adjustment for CVD risk factors. Conclusions Excellent overall survival was observed in TC patients. The most common cause of death was TC-specific mortality, suggesting the importance of thyroid cancer treatment. The overall and cause-specific mortality risks, particularly CVD mortality risk, did not differ between TC patients and the general population.

BACKGROUND Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals. METHODS We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO. RESULTS During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged

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 P Conclusions Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes. Graphical Abstract

BackgroundOptimal treatment for persistent Graves’ disease following 12–18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.MethodsThis retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.ResultsThere were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60–4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20–1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38–1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend < 0.001).ConclusionsIn patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves’ disease.

OBJECTIVE: This study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to coronavirus disease 2019 (COVID-19) outcomes. METHODS: We analyzed 4,069 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 obese (MHO), and metabolically unhealthy obese (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 severe COVID-19 outcomes 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 severe 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 severe COVID-19 increased insignificantly by 2% per 1 kg/m2 BMI increase but significantly by 13% per 1 metabolically unhealthy component increase, even after mutually adjusting for BMI and metabolic health status. CONCLUSION: Metabolic health is more important to COVID-19 outcomes than obesity.

Despite the association between sarcopenia and non-alcoholic fatty liver disease (NAFLD), no study has evaluated the predictive role of NAFLD in sarcopenia. We investigated impact of NAFLD on the risk of low muscle mass (LMM) and low muscle strength (LMS) in a nationwide multicenter study. A total of 1595 community-dwelling people aged 70–84 years were followed for 2 years in the Korean Frailty and Aging Cohort Study. Muscle mass was estimated by dividing appendicular skeletal muscle mass (ASM) by body mass index (BMI). Muscle strength was measured as handgrip strength (HGS) divided by BMI. The sex-specific lowest quintiles of ASM/BMI and HGS/BMI of the study population were used as cutoffs for LMM and LMS, respectively. The risk of LMM and LMS were assessed according to hepatic steatosis index (HSI) and fatty liver index (FLI) quartiles. As HSI quartiles increased, the LMM risk increased gradually, after adjusting for age, sex, lifestyle factors, comorbidities, and several causative factors (insulin resistance, inflammation, and vitamin D) (Q4 vs. Q1 OR [95% CI] 3.46 [2.23–5.35]). The increased risk of LMS was even higher according to HSI quartiles (Q4 vs. Q1 5.81 [3.67–9.21]). Multivariate analyses based on FLI showed similar results. People with NAFLD (HSI > 36) were at higher risk of developing LMM and LMS compared to those without (1.65 [1.19–2.31] and 2.29 [1.61–3.26], respectively). The presence of NAFLD may predict future risk of LMM and LMS, with greater impact on LMS than on LMM.

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.

Physical exercise plays an important role in both the prevention and treatment of cardiometabolic diseases. Peptides secreted or released from skeletal muscle, so-called myokines, contribute to the beneficial anti-inflammatory and insulin-sensitizing effects of increased muscle activity and may, therefore, counteract pathomechanisms of obesity and type 2 diabetes (T2D) [1]. However, the impact of myokines including interleukin (IL)-6, IL-8, IL-13, IL-15, angiopoietin-like 4 (ANGPTL4), fibroblast growth factors (FGF)-2, FGF-21, and irisin on altered organ cross-talk in cardiometabolic diseases is still poorly understood [1]. Irisin has been described as a protein released from skeletal muscle after physical activity [2] which may, in rodents and more controversially discussed in humans [1], mediate browning of white adipose tissue. Although the existence of circulating human irisin has even been questioned because human FNDC5 has a noncanonical ATA translation start, irisin has been detected in human plasma using mass spectrometry with appropriate control peptides [3]. IL-15 increases upon both aerobic and resistance exercise and exerts beneficial metabolic effects in patients with obesity and T2D [1]. IL-15 inhibits lipogenesis, induces fat oxidation, enhances energy expenditure, and improves insulin sensitivity and glucose metabolism [4]. To better understand the potential role of these myokines in T2D, we tested the hypotheses that IL-15 and irisin serum concentrations correlate with cardiometabolic risk parameters and are different in subgroups of T2D patients with or without diabetes complications independently of ethnicity.

Background Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)–induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress–related cardiac diseases.

Protectin DX (PDX), which is a novel regulator of 5' adenosine monophosphate-activated protein kinase (AMPK), has recently gained attention for its ability to improve several metabolic diseases. However, the function of PDX in vascular endothelial cells remains unclear. To confirm the protective effects of PDX on endothelial oxidative stress, human umbilical vein endothelial cells (HUVECs) were treated with hydroperoxide (H2O2) and PDX. PDX treatment significantly increased the level of AMPK phosphorylation, and this elevation was attenuated after treatment with G-protein coupled receptor 120 (GPR120) antagonist or GPR120 knockdown. Expressions and activities of antioxidant proteins, including catalase and superoxide dismutase 2 (SOD2), were elevated by PDX and were inhibited by treatment with AMPK inhibitor or with GPR120 antagonist. Production of H2O2-induced reactive oxygen species (ROS), the Bax/Bcl-2 ratio, and the loss of mitochondrial membrane potential were all reversed by PDX, leading to improved cell viability and reduced release of lactate dehydrogenase (LDH). Using flow cytometry, we also found that PDX significantly reduced the H2O2-induced apoptotic population of cells. These protective effects of PDX were all reversed after treatment with AMPK inhibitor or GRP120 antagonist. These results show that the PDX-AMPK axis has a protective role against H2O2-induced oxidative stress in vascular endothelial cells.

Background: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naive newly-diagnosed type 2 diabetes mellitus. Methods: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was mea sured at week 24. Results: The reduction in the levels of HbA1c was -1.62%±0.07% in the vogmet group and -1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of

Possible links between periodontitis and various cardiometabolic and autoimmune diseases have been advocated on the basis of chronic inflammation or oxidative stress. However, the association between periodontitis and thyroid dysfunction is under-researched. Participants without previous thyroid disease or ongoing thyroid-related medication were included from a nationwide population-level survey. Participants were categorized into tertiles of thyroid stimulating hormone (TSH) levels (first tertile 2.83 mIU/L), and periodontal condition was assessed using the Community Periodontal Index. Of the total of 5468 participants, 1423 had periodontitis (26%). A significant difference in the weighted prevalence of periodontitis according to TSH tertiles was observed, with the highest prevalence in the first tertile (26.5%) and the lowest prevalence in the third tertile (20.9%, p = 0.003). Subjects in the first TSH tertile had higher odds for periodontitis than those in the third tertile (OR 1.36, 95% CI 1.10–1.68; p for trend = 0.005) after adjusting for covariates. This association was consistent across subgroups and within sensitivity analyses among subjects without specific factors affecting thyroid function or diseases reported to be related to periodontitis. The present study demonstrated that low TSH levels were associated with significantly higher odds for periodontitis.

BackgroundThe 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.MethodsIn 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.ResultsThe 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 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 ConclusionsLong working hours was significantly associated with NAFLD. Further prospective studies are required to validate this finding with causal relationship.

Aim Although few recent studies have reported the association between the glycemic variability and the development of type 2 diabetes mellitus and cardiovascular disease in individuals without diabetes mellitus, the impact of the long-term variability in fasting plasma glucose (FPG) levels on the incident nonalcoholic fatty liver disease (NAFLD) has not been evaluated. Methods The study included 57,636 Korean men and women without NAFLD and diabetes mellitus from the Korean National Health Insurance System cohort. FPG variability was calculated using the coefficient of variation (FPG-CV), standard deviation (FPG-SD), variability independent of the mean (FPG-VIM), and average successive variability (FPG-ASV). Results The cumulative incidence of NAFLD demonstrated progressively increasing trends according to the higher quartiles of FPG variability in Kaplan-Meier curves. A multivariable Cox proportional hazard analysis revealed that the hazard ratio for incident NAFLD was 1.15 (95% confidence interval, 1.06–1.24) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for various confounding factors, including mean FPG levels. When using FPG-SD, FPG-VIM, and FPG-ASV, the results were similar. The 10-unit increase in FPG variability was associated with a 14% increased risk of NAFLD in the fully adjusted model. Moreover, this effect remained consistent in the subgroup and sensitivity analyses. Conclusion Increased long-term FPG variability is associated with the development of NAFLD, independent of confounding risk variables including mean FPG levels.

Objective We investigated the effects of statin-ezetimibe combination therapy compared with statin-only treatment on the hazard of incident type 2 diabetes (T2D), myocardial infarction (MI), and stroke among adults with impaired fasting glucose (IFG) in a real-world setting. Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this propensity-matched nationwide cohort study. Among 56,633 IFG patients without baseline cardiovascular disease (CVD) and/or T2D who initiated statin therapy with or without ezetimibe, 1,155 with statin-ezetimibe combination therapy were matched based on a propensity score at a 1:5 ratio with 5,775 patients who received statin monotherapy. The hazards of T2D, MI, and stroke were compared between these treatment groups. Results The incidence rate per 1,000 person-years was 19.62 (statin monotherapy group) and 21.02 (combined treatment group) for T2D, 1.53 (statin monotherapy group) and 1.70 (combined treatment group) for MI, and 1.99 (statin monotherapy group) and 2.06 (combined treatment group) for stroke. The hazards of T2D, MI, and stroke were not significantly different between the statin monotherapy group and the statin-ezetimibe combination therapy group. Conclusion The combination of ezetimibe in addition to statin treatment was not associated with a significantly different risk of T2D and CVDs compared with statin monotherapy in Korean adults with IFG.

Context Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. Objective We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. Methods Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). Results Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. Conclusion FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.

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.

The effect of blood pressure (BP) on the incident cardiovascular events, progression to end-stage renal disease (ESRD) and mortality were evaluated among chronic kidney disease (CKD) patients with and without antihypertensive treatment. This nationwide study used the Korean National Health Insurance Service-Health Screening Cohort data. The hazards of outcomes were analysed according to the systolic BP (SBP) or diastolic BP (DBP) among adults (aged ≥ 40 years) with CKD and without previous cardiovascular disease or ESRD (n = 22,278). The SBP and DBP were ≥ 130 mmHg and ≥ 80 mmHg in 10,809 (48.52%) and 11,583 (51.99%) participants, respectively. During a median 6.2 years, 1271 cardiovascular events, 201 ESRD incidents, and 1061 deaths were noted. Individuals with SBP ≥ 130 mmHg and DBP ≥ 80 mmHg had higher hazards of hypertension-related adverse outcomes compared to the references (SBP 120–129 mmHg and DBP 70–79 mmHg). SBP

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.

We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.

INTRODUCTION: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM. METHODS: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements. RESULTS: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18–1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend