AIMS:To evaluate the efficacy and safety of adding a fourth oral antidiabetic drug versus metformin uptitration in patients with type 2 diabetes inadequately controlled with oral triple therapy. MATERIALS AND METHODS:In this 24-week, randomized, open-label trial, adults with type 2 diabetes having glycated haemoglobin (HbA1C) 7.0-9.0% despite oral triple therapy with metformin plus a thiazolidinedione (TZD), sodium-glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP-4i) were randomized to an oral quadruple add-on group or a metformin uptitration group. The quadruple group received the class not previously used (TZD, SGLT2i, or DPP-4i), whereas the metformin uptitration group increased the metformin dose by up to 500 mg per day. The primary endpoint was the change in HbA1C at week 24. Secondary endpoints included fasting glucose, metabolic parameters, and safety. RESULTS:Hundred and ninety-three were evaluable: 48 in the metformin uptitration group and 145 in the quadruple group. Compared to baseline, HbA1C at week 24 decreased by 0.70% (interquartile range [IQR] 0.40%, 1.10%) with quadruple therapy and 0.40% (IQR 0.10%, 0.80%) with metformin uptitration (p = 0.002). The rate achieving HbA1C ≤7.0% was higher in the quadruple group (69.7% vs. 47.9%, p = 0.006). Insulin resistance improved only in the quadruple group and was accompanied by reduced albuminuria. Adverse events were mild and comparable between groups. CONCLUSIONS:Oral quadruple therapy achieved greater glycaemic and metabolic improvement without compromising safety, compared with metformin uptitration, supporting its role as an intensification strategy.

AIMS:To assess the efficacy and safety of alpha-lipoic acid (ALA) and pregabalin, both as mono and combination therapy, for treating painful diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus, with the hypothesis that pregabalin monotherapy is non-inferior to combination therapy. MATERIALS AND METHODS:A phase 4 randomized, active-controlled, open-label, multicentre trial was conducted over 12 weeks to investigate changes in visual analogue scale (VAS) pain scores from baseline as a primary efficacy endpoint. A total of 151 eligible subjects were randomly assigned to ALA (480 mg/day), pregabalin (150 mg/day), and combination groups in a 1:1:1 ratio. RESULTS:The pregabalin monotherapy group showed a VAS change of -19.73 ± 18.94 mm, while the combination group showed -23.28 ± 18.15 mm at Week 12. The least square mean (LSM) difference between the two groups was 3.46 mm (95% CI: [-4.94, 11.87]), demonstrating that pregabalin monotherapy is non-inferior to combination therapy. Safety analysis revealed no significant differences across treatment groups. Cluster analysis revealed statistically significant differences in VAS scores between the pregabalin monotherapy and combination therapy groups at 12 weeks in cluster 1, characterized by a relatively shorter duration of DPN, and the LSM difference between both groups was 14.79 mm [4.59, 24.99] (p = 0.0055). CONCLUSIONS:The pregabalin monotherapy demonstrated non-inferiority compared to the combination therapy in alleviating DPN pain. Cluster analysis supported the identification of patient groups where combination therapy could be more effective, but future comprehensive studies are required for further verification. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04846673.

Background Suicide represents a major public health concern in Korea. Patients with type 2 diabetes mellitus (T2DM) are at higher risk for psychological distress and suicide. Although the male-to-female suicide mortality ratio in the general population has remained about 2.3, the specific differences in suicide mortality by sex among individuals with T2DM are not well characterized. Methods We performed a nationwide cohort study utilizing the Korean National Health Insurance Service database, identifying 2,526,769 adults with T2DM who underwent health screening from 2015 to 2016. Participants were monitored until the occurrence of suicide or the study endpoint. Results During a median follow-up of 6.0 years, 5,584 suicide deaths occurred (0.30% in men vs. 0.10% in women). Men exhibited a significantly elevated risk of suicide mortality compared to women (adjusted hazard ratio [HR], 2.88; 95% confidence interval [CI], 2.66 to 3.12). The largest disparity was observed in the ≥80 age group (HR, 3.60; 95% CI, 2.88 to 4.51). However, this sex disparity in suicide mortality was reduced among current smokers and heavy alcohol consumers. Among non-smokers, the HR comparing men to women was 3.51 (95% CI, 3.22 to 3.83), while among current smokers, it was 1.73 (95% CI, 1.40 to 2.14). Similarly, the HR among non-drinkers was 3.04 (95% CI, 2.79 to 3.31), compared with 1.36 (95% CI, 0.85 to 2.18) among heavy drinkers. Conclusion Men with T2DM had a significantly higher risk of suicide mortality than women, exceeding the sex disparity seen in the general population, with the gap further influenced by age and lifestyle factors.

Objectives The long-term health impact of mandatory school-based physical activity remains poorly understood. This study aimed to investigate the association between mandatory physical fitness test exposure and metabolic health outcomes in adolescents and adults. Study design Repeated cross-sectional study utilized data from the National Health Information Database from 2009 to 2017. Methods We conducted two age-based cohorts: a 35.5-year-old cohort who transitioned from full physical fitness test exposure in 2009 to no exposure in 2017, and a 45.5-year-old cohort who had been fully exposed to the physical fitness test. Results During the study period, the 35.5-year-old cohort showed pronounced increases in both obesity and central obesity. In males, the adjusted obesity prevalence increased from 41.5% to 50.8% in the 35.5-year-old cohort and from 38.2% to 45.8% in the 45.5-year-old cohort, with a greater absolute increase (9.3% vs. 7.6%; P interaction <0.0001). Central obesity increased from 20.4% to 31.0% in the 35.5-year-old cohort, and from 19.7% to 25.9% in the 45.5-year-old cohort (10.7% vs. 6.3%). In females, obesity and the prevalence of central obesity remained stable in the 45.5-year-old cohort. However, the 35.5-year-old cohort exhibited a steeper secular increase in the obesity and central obesity prevalences (from 19.0% to 23.7% and from 10.1% to 14.9%, respectively). Conclusions The abolition of the mandatory physical fitness test was associated with a rapid obesity and central obesity increase. The long-term public health consequences of discontinuing mandatory physical activity programs needed for new strategies to mitigate the burden of metabolic diseases in younger generations.

BACKGROUND:Type 2 diabetes mellitus (T2DM) is a progressive, multi-organ disorder that often requires intensive combination therapy. This Phase III, randomised, double-blind, placebo-controlled study evaluated the efficacy and safety of two fixed-dose combinations (FDCs) of sitagliptin 100 mg with empagliflozin 10 mg (DW1026C1) or empagliflozin 25 mg (DW1026C2) as add-on therapy for patients with inadequately controlled T2DM. METHODS:Two hundred thirty adults with T2DM inadequately controlled by metformin (≥ 1000 mg/day) and sitagliptin (100 mg) were 1:1:1 randomised to receive DW1026C1 (E10 group, n = 77), DW1026C2 (E25 group, n = 76), or a placebo (n = 77). Treatment was administered for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c from baseline to Week 24. RESULTS:Baseline characteristics were similar among groups. At Week 24, both active treatments demonstrated statistically significant HbA1c reductions versus the placebo. The least square mean differences [95% CI] versus the placebo were -0.54% [-0.78, -0.29] for E10 group and -0.61% [-0.85, -0.36] for E25 group (both p < 0.0001). Fasting plasma glucose (FPG), insulin resistance, body weight, systolic blood pressure, albumin-creatinine ratio and high-density lipoprotein cholesterol also improved in the active groups. Reductions in HbA1c, FPG and insulin resistance were sustained in Week 52. Safety profiles were favourable with adverse events similar in frequency and no increased hypoglycaemia risk. CONCLUSION:Sitagliptin/empagliflozin FDC doses achieved improvements in glycaemic control at 24 weeks, which was maintained through 52 weeks. These benefits were accompanied by a favourable safety profile, including a very low risk of hypoglycaemia. TRIAL REGISTRATION:NCT07076056.

ABSTRACT Aim This study aimed to evaluate the prevalence, clinical characteristics, and factors associated with cardiovascular autonomic neuropathy (CAN) in Korean individuals with long‐standing type 2 diabetes mellitus (T2DM). Methods A total of 876 participants with long‐standing T2DM were enrolled in this multicenter cross‐sectional study. CAN was evaluated using standard cardiovascular autonomic reflex tests (CARTs) and corrected QT interval (QTc), with additional heart rate variability (HRV) analysis. CAN severity was classified as early, definite, or severe. Multivariable logistic regression analysis was performed to identify factors independently associated with CAN. Results CAN was detected in 88.4% of participants. Individuals with CAN showed reduced HRV indices and prolonged QTc intervals. Multivariable analysis revealed advanced age (OR = 1.062; 95% CI: 1.035–1.091; p < 0.0001) and higher systolic blood pressure (OR = 1.036; 95% CI: 1.022–1.051; p < 0.0001) as factors independently associated with CAN. Conclusion CAN is highly prevalent among Korean individuals with long‐standing T2DM. Older age and elevated systolic blood pressure were independently associated with CAN, highlighting the importance of routine CAN screening and careful blood pressure management.

INTRODUCTION:To evaluate glycemic changes during caloric restriction with continuous glucose monitoring (CGM)-derived time in range (TIR) in individuals with type 2 diabetes and obesity. MATERIALS AND METHODS:This 12-week single-arm intervention consisted of 6 weeks of home-delivered meals (800-1,200 kcal/day), followed by 6 weeks of self-managed diet (1,500-1,800 kcal/day for men; 1,200-1,500 kcal/day for women). CGM (14-day sensor) was performed at baseline, weeks 5-6, and weeks 11-12. A 75-g oral glucose tolerance test was conducted at baseline, week 6, and week 12 to calculate the C-peptide index (CPI) and Matsuda index. RESULTS:Participants had a median age of 46.0 years [38.0, 53.5], body mass index (BMI) of 29.2 kg/m2 [26.8, 31.2], HbA1c 6.6% [6.0, 7.13], and diabetes duration 2.01 years [0.91, 3.65]. Over 12 weeks, TIR improved from 84.3% to 90.3% (P = 0.041), and BMI decreased from 29.3 to 26.7 kg/m2 (P < 0.001). Weight reduction was associated with improved insulin sensitivity, whereas changes in CPI were not significant. CPI showed a stronger association with TIR than the Matsuda index, underscoring the importance of insulin secretion capacity in glycemic control. The association between CPI and TIR was more pronounced participants with higher insulin sensitivity (P = 0.011), suggesting that adequate peripheral sensitivity is required to influence glycemic outcomes. CONCLUSIONS:In individuals with type 2 diabetes and obesity, caloric restriction was associated with improved glycemic profiles and reduced body weight. Enhanced insulin sensitivity appears to be the predominant contributor to improved TIR, while preserved β-cell function remains essential for achieving optimal glycemic outcomes.

Background/Aims: Parathyroid hormone–related protein (PTHrP) is a major mediator of hypercalcemia in patients with malignancy; however, understanding of PTHrP-mediated hypercalcemia remains limited because available evidence has largely been derived from small case series.Methods: We retrospectively analyzed electronic medical records from eight hospitals affiliated with The Catholic University of Korea. Adult patients (> 20 years) with confirmed malignancy and albumin-corrected hypercalcemia (≥ 10.5 mg/dL) between 2013 and 2022 were identified and classified as having PTHrP-mediated hypercalcemia (PTHrP > 1.1 pmol/L) or hypercalcemia due to other causes (PTHrP ≤ 1.1 pmol/L).Results: Among the 289 patients reported to have PTHrP-mediated hypercalcemia, median age was 66 years (interquartile range [IQR], 59–75) and median plasma PTHrP level was 6.1 pmol/L (IQR, 3.5–11.5). Solid tumors accounted for 86% of cases, while hematologic malignancies accounted for the other 14%. The most common cancer types were lung cancer (30%, n = 87), head and neck cancer (11%, n = 31), and multiple myeloma (8%, n = 24). Median survival after the onset of hypercalcemia was 46 days (95% confidence interval [CI], 36–61) in patients with PTHrP-mediated hypercalcemia. Compared with the 169 patients with hypercalcemia due to other causes, PTHrP-mediated hypercalcemia was associated with a higher risk of mortality after adjustment for age, corrected calcium level, and cancer type (adjusted hazard ratio, 4.0; 95% CI, 2.9–5.4).Conclusions: PTHrP-mediated hypercalcemia occurs across a broad spectrum of malignancies and is associated with worse clinical outcomes.

Background: The contribution of adiposity and metabolic syndrome (MetS) to thyroid cancer risk in late life, particularly among the elderly, is unclear. Methods: We conducted a nationwide cohort study of Korean adults aged ≥75 years who underwent standardized health screening. Exposures were body mass index (BMI), waist circumference (WC), and MetS defined by standard clinical criteria. The incidence of thyroid cancer was determined using administrative data. Fine-Gray sub-distribution hazard models estimated adjusted hazard ratios (HRs) with prespecified stratification by sex and age (75-84 vs. ≥85 years). Results: Among 1,164,707 participants (60.3% women), 2645 incident cases were identified. In the fully adjusted models, obesity (BMI ≥ 25 kg/m2) was associated with a 37% higher hazard (HR, 1.37; 95% confidence interval [CI], 1.27-1.49) and MetS with an 18% higher hazard (HR, 1.18; 95% CI, 1.09-1.28). In sex-stratified models, MetS was associated with thyroid cancer in women (HR 1.19; 95% CI, 1.08-1.31) and showed a similar direction of association in men (HR 1.16; 95% CI, 1.00-1.35), with overlapping CIs. By age, associations were evident at 75-84 years (MetS: HR, 1.18; obesity: HR, 1.36), whereas at ≥85 years, only obesity remained significant (HR, 1.90; 95% CI, 1.13-3.18). Among MetS components, high WC showed the most consistent association (HR, 1.31; 95% CI, 1.21-1.42). Conclusions: In adults aged ≥75 years, general obesity and, in particular, central adiposity are robustly associated with incident thyroid cancer, whereas metabolic syndrome confers a more modest and mainly age- and sex-specific additional risk.

BACKGROUND:Despite the increasing use of continuous glucose monitoring (CGM) systems, limited data exist on their perceived benefits and challenges among patients and healthcare providers. This study explored CGM-related experiences in South Korea. METHODS:An anonymous online survey was conducted between January and December 2021 at four university hospitals. Respondents included patients with diabetes mellitus (DM), physicians, and DM education nurses. The survey assessed the use of CGM, its benefits, and barriers. Most devices were first-generation CGMs: FreeStyle Libre 1 (Abbott Diabetes Care), Dexcom G6 (Dexcom Inc.), and Medtronic Guardian 3 (Medtronic MiniMed). RESULTS:Among 1,010 patients (33.4% with type 1 DM [T1DM], 63.6% with type 2 DM [T2DM], and 3.1% others; mean age, 51.4±14.6 years), 92.7% found CGM helpful. Although 59.6% reported discomfort, 81.9% intended to continue using CGM, indicating that perceived benefits outweighed barriers. The key advantages were glucose monitoring without finger pricks (T1DM, 57.9%; T2DM, 56.2%) and maintenance of target glucose levels. Discomfort was related to discomfort during activities (53.8%), skin problems (45.0%), and pain (43.0%). Healthcare provider recommendations were associated with reduced discomfort (adjusted odds ratio, 0.36; 95% confidence interval, 0.21-0.60). Physicians (n=29) cited high costs as the main barrier (T1DM, 58.9%; T2DM, 64.8%); only 51.9% and 14.5% prescribed CGM for T1DM and T2DM, respectively. Insulin adjustment and glucose control were the main reasons for prescription, while cost (89.3%) and limited consultation time (67.9%) were barriers. DM educators (n=9) reported heavy workloads, with training and follow-up times averaging 31.7±7.5 minutes and 21.7±9.7 minutes, respectively; 77.8% of DM educators identified frequent patient inquiries as their greatest burden. CONCLUSION:CGM provides significant clinical benefits but is limited by discomfort, costs, and educational burden. Sustained adoption requires device improvements, insurance support, and workforce expansion.

Background Despite their efficacy, statin-related adverse events (AEs) may interfere with statin treatment and contribute to negative outcomes in patients with cardiovascular diseases. In this study, we evaluated the safety and effectiveness of pravastatin in Korea. Methods Pooled data were collected from four multicenter prospective observational studies conducted in Korea between 2011 and 2020. Finally, 7,334 and 2,022 participants were included in the safety and effectiveness analyses, respectively. Overall safety, particularly muscle-related, incidence of new-onset diabetes mellitus (DM), changes in fasting plasma glucose and hemoglobin A1c level, achievement of target low-density lipoprotein cholesterol (LDL-C) level, and changes in LDL-C level were analyzed. Results At week 24, after 20 or 40 mg pravastatin treatment, safety results showed that AEs and adverse drug reactions (ADRs) were 8.7% and 1.3%, respectively, and that muscle-related AEs and ADRs were 0.5% and 0.3%, respectively, with no statistically significant difference in risk factors for statin-associated muscle symptoms. No patients developed DM during the study period. Additionally, at week 24, the achievement rates of target LDL-C levels were 87.9%, 78.4%, 57.8%, and 11.6% in low-, moderate-, high-, and very high-risk groups, respectively. Conclusion This study found that 20 or 40 mg pravastatin had minimal side effects and was safe for use in real-world clinical settings in Korea. Specifically, these doses effectively achieved the target LDL-C levels in patients with dyslipidemia in low-, moderate-, and high-risk groups for atherosclerotic cardiovascular disease (ASCVD). These results demonstrate that pravastatin can be safely administered continuously to patients with low-, moderate-, and high-risk ASCVD in a real-world clinical setting.

The association between blood pressure (BP) and its variability (BPV) with psychological disorders has been established. We aimed to investigate whether this relationship extends to the risk of suicide in a large, nationally representative cohort. This retrospective cohort study included 1,983,107 participants from the Korean National Health Insurance Service database, collected between 2005 and 2009, with 11.1 years of follow-up. BPV was assessed using at least three health examination datasets and validated variability indices (variability independent of the mean [VIM], average successive variability, and coefficient of variation). The primary endpoint was suicide-related death. Cox proportional hazards models were used to estimate hazard ratios (HRs) for suicide across BPV quartiles. Higher BP and BPV were significantly associated with an increased risk of suicide. Participants in the highest quartile (Q4) of systolic BPV (VIM) had an adjusted HR of 1.13 (95% CI: 1.05-1.22) for suicide. Similarly, those in Q4 of diastolic BPV (VIM) had an HR of 1.16 (95% CI: 1.08-1.24). This association was particularly pronounced in older adults (≥65 years), with an HR of 1.18 (95% CI: 1.03-1.36) for systolic BPV and 1.21 (95% CI: 1.05-1.39) for diastolic BPV in Q4. Consistent findings were observed when using different variability indices. Subgroup analyses according to sex, diabetes, depression, hypertension, and use of antihypertensive medications also supported these findings. These findings suggest that both BP and BPV are novel risk factors for suicide mortality. Considering BP and BPV together may enhance the identification of individuals at higher risk of suicide.

Background/Objectives: Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut–kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients. Methods: We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed. Results: Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034–2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046–4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209–3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141–5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455–3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139–6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163–10.554, p < 0.0001) compared to those with low levels of both markers. Conclusions: FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD.

Introduction and Objective: Suicide is a major global concern, and people with type 2 diabetes (T2D) are particularly at risk due to the stress and difficulties of managing their disease. Smoking adds to this burden, but the impact of smoking on suicide risk in people with T2D is not well understood. This study aimed to investigate the association between smoking and suicide in people with T2D to help inform preventive measures. Methods: This longitudinal cohort study utilized data from the Korean National Health Insurance Service (NHIS) database. A total of 2,524,769 patients with T2D aged 20 years or older who underwent a national health examination in 2015-2016 were included in the study. Participants were followed up until suicide or the end of the study. Results: During a mean follow-up of 5.8 years, 5,578 people (0.22%) died by suicide. Current smokers had a significantly higher risk of suicide compared to never-smokers (adjusted hazard ratio [HR]: 1.55). Ex-smokers did not have a significantly increased risk after adjustment, except for those with a smoking history of 30 years or more (HR: 1.12). Subgroup analysis showed that women who were current smokers had a significantly higher risk (HR: 2.71) compared to men (HR: 1.47). For participants aged 65 and older, current smoking did not significantly increase the risk of suicide (HR: 1.13, 95% CI: 0.99-1.28), unlike those under 65 (HR: 1.78, 95% CI: 1.61-1.92). Conclusion: Current smoking significantly increases the risk of suicide in people with T2D, especially among women and younger people. A long-term smoking history further increases the risk, emphasizing the need to quit smoking in this high-risk population. H. Kwon: None.

Background This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration. Methods We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders. Results Over 6,967,381 person-years of follow-up, 7,548 participants developed ESRD. Higher TyG index quartiles were independently associated with increased risk of ESRD, which was more pronounced with longer diabetes duration. The adjusted HR for ESRD in the highest TyG quartile (Q4) compared to the lowest quartile (Q1) was 1.235 (95% confidence interval [CI], 0.995 to 1.533) in new-onset diabetes, and 1.592 (95% CI, 1.465 to 1.730) in those with diabetes for ≥10 years. Compared to the lowest TyG quartile in new-onset diabetes, the adjusted HR for ESRD in the highest quartile with diabetes duration ≥10 years increased to 10.239 (95% CI, 8.440 to 12.422). Subgroup analysis revealed that a higher TyG index consistently increased the risk of ESRD, with stronger associations observed in younger individuals and those without comorbidities. Conclusion The TyG index is a significant predictor of ESRD in T2DM, particularly in those with prolonged diabetes duration. Targeting insulin resistance early may mitigate the risk of ESRD in this population.

Abstract Background Suicide is a significant yet preventable public health issue. Body mass index (BMI) is a readily measurable indicator associated with various health outcomes. However, the relationship between BMI and suicidal death risk is complex and warrants further investigation, particularly within contemporary, non-Western contexts with consideration of potential confounders. The purpose of this study was to investigate the relationship between BMI and the risk of suicidal death. Methods This study was nationwide, retrospective, observational study based on Korean National Health Insurance Service database. We analyzed 4,045,081 participants who were aged > 19 years and underwent national health surveillance in 2009. The participants were categorized according to their BMI (underweight: < 18.5 kg/m², normal weight: 18.5–23 kg/m², overweight: 23–25 kg/m², class I obesity: 25–30 kg/m², and class II obesity: > 30 kg/m²). The primary outcome was the death events caused by suicide which was defined by International Classification of Disorders (ICD-10) codes (X60–X84) and death records documented by the Korea National Statistical Office. Multivariate Cox proportional hazard regression analysis was performed to estimate the risk of suicidal death with respect to BMI categories after adjusting for potential confounders (age, sex, income, diabetes, hypertension, dyslipidemia, smoking, drinking, exercise, self-abuse, waist circumference, schizophrenia, bipolar disorder, eating disorder, cancer, anxiety, and substance use disorder). Results Underweight individuals had an increased risk (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.31–1.57) while overweight (HR 0.79, 95% CI 0.76–0.83), class I (HR 0.76, 95% CI 0.71–0.80) and class II obesity (HR 0.71, 95% CI 0.63–0.81) were associated with decreased risks of suicidal deaths compared to those of the normal weight individuals (BMI 18.5–23). This trend was consistent regardless of the presence of major depressive disorder (MDD) or the type of living arrangements of the participants. Conclusions Suicidal death risk was inversely correlated with BMI categories, independent of MDD or living arrangements. Our data suggests the importance of physiological factors associated with body mass in understanding suicidal death risk. Furthermore, these data provide valuable insights to where the public health resources should be invested to reduce suicidal death rates.

Background We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients. Methods A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles. Results Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers. Conclusion The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.

The effects of psychological resilience and depressive symptoms on bone health have not been well-studied. This work aimed to evaluate the association between psychological resilience and depressive symptoms on bone mineral density (BMD) and osteoporotic fracture in community-dwelling adults in Korea. Data from the Chungju Metabolic Disease Cohort were used. Between May 2007 and March 2011, 4029 participants aged 40 years or older underwent a baseline examination, and approximately four years later, they underwent a second examination. BMD was measured, and resilience and depression scales were completed. Participants in the lowest resilience group had lower BMD Z-scores at the femoral neck (0.04 ± 0.53 vs. 0.22 ± 0.950, p < 0.001) and the total hip (0.17 ± 0.98 vs. 0.34 ± 0.92, p < 0.001) compared to those in the highest resilience group. Individuals with clinical depression also had lower BMD Z-scores than those without it. However, resilience status was not associated with the prevalence of osteoporosis at follow-up or incident fracture. In contrast, the odds of osteoporosis were 1.39 (95% CI 1.12-1.71) in women with clinical depression even after adjusting for covariates. In men, clinical depression was not associated with the odds of osteoporosis. Among non-osteoporotic participants, subjects with clinical depression had a 1.40-fold (95% CI 1.07-1.92) higher fracture incidence than those without depression. In this study, low resilience did not appear to negatively affect the prevalence of osteoporosis at follow-up or fracture. Among non-osteoporotic participants, depressive individuals have a potentially increased risk of fracture compared with those without clinical depression.

BACKGROUND:Moyamoya vasculopathy (MMV) is a rare cerebrovascular disease of unclear cause. In this study, we aimed to determine whether metabolic syndrome (MetS) is associated with the development of MMV and subsequent stroke risk in young adults. METHODS:Using a nationwide database, we retrospectively analyzed the data of 6 891 400 Korean adults aged 20 to 40 years who underwent health screening between 2009 and 2012. Participants were monitored until December 31, 2021, to identify patients newly diagnosed with MMV. We further examined the risk of ischemic and hemorrhagic stroke in patients newly diagnosed with MMV without prior stroke. Hazard ratios (HR) were calculated using multivariable Cox regression models adjusted for relevant confounders. RESULTS:Over a median follow-up of 9.65 years, 1754 individuals developed MMV. These participants exhibited significantly poorer baseline metabolic profiles, including a higher body mass index and a higher prevalence of diabetes, hypertension, and dyslipidemia (all P < 0.0001). Metabolic syndrome was associated with a significantly increased risk of MMV development (adjusted HR, 2.94 [95% CI, 2.60-3.33]). The association between metabolic derangements and MMV risk was stronger in women. Among newly diagnosed patients with MMV, metabolic syndrome was associated with an increased risk of subsequent stroke (adjusted HR, 2.05 [95% CI, 1.25-3.37]), primarily ischemic stroke. CONCLUSIONS:Metabolic syndrome could substantially increase the risk of MMV development and subsequent stroke events in young adults. These findings emphasize the importance of managing metabolic health to prevent MMV and related neurological outcomes.