Young Sang Lyu

Background and Objectives: Evidence on the association between sleep duration and obesity phenotypes jointly considering adiposity and metabolic health is limited, particularly in adults without known chronic diseases. We aimed to examine this association in apparently healthy Korean adults. Materials and Methods: In this cross-sectional study, we analyzed 7808 apparently healthy adults aged ≥20 years from the Korea National Health and Nutrition Examination Survey 2013–2015, assigned to metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obesity (MHO), or metabolically abnormal obesity (MAO) phenotypes. Self-reported sleep duration was grouped as ≤5, 6, 7, 8, or ≥9 h/day. Survey-weighted multinomial logistic regression was performed with MHNW and ≥9 h as references, adjusting for age and sex (Model 1) and socioeconomic and lifestyle factors (Model 2). Sensitivity analyses used 7 h/day as the reference and a stricter definition of metabolic health; effect modification by sex and age was examined. Results: The proportion of MHNW increased from 61.6% (≤5 h) to 76.0% (≥9 h) (p < 0.001). In Model 2, sleeping ≤5 h was associated with higher odds of MHO (odds ratio [OR] 1.380, 95% confidence interval [CI] 1.098–1.734) and MAO (OR 1.472, 95% CI 1.109–1.953) relative to 7 h, and these associations remained significant after false discovery rate correction, whereas none of the associations relative to ≥9 h, including that with MANW, did. Under the stricter definition, the association with MAO persisted, whereas that with MHO was no longer statistically significant despite a similar effect estimate (vs. 7 h: OR 1.394, 95% CI 0.926–2.098); no significant interactions by sex or age were observed for MHO or MAO. Conclusions: In apparently healthy Korean adults, short sleep duration was associated with higher odds of MHO and MAO, most consistently MAO, but not robustly with MANW. Because of the cross-sectional design, these associations do not imply causality, and prospective studies are needed to determine whether sleep duration is a modifiable target for metabolic health.

Background/Objectives: Periodontitis and diabetes are closely linked; however, whether periodontal findings are associated with previously unrecognized dysglycemia in adults without known chronic diseases remains unclear. We examined the association between periodontal status and undiagnosed prediabetes and diabetes in this population. Methods: We analyzed data from 7635 adults (3218 men and 4417 women) aged ≥19 years without self-reported physician-diagnosed chronic diseases who participated in the Korea National Health and Nutrition Examination Survey 2013–2015. Glycemic status was classified as normal, undiagnosed prediabetes, or undiagnosed diabetes based on a single measurement of fasting plasma glucose and glycated hemoglobin. Periodontal status was determined with the Community Periodontal Index (CPI) and grouped as CPI 0–2, CPI 3, or CPI 4. Survey-weighted multivariable logistic regression analyses were performed in men and women separately, and effect modification by sex was formally tested. Results: Undiagnosed prediabetes and diabetes were present in 42.0% and 5.0% of men and in 31.7% and 2.9% of women (weighted estimates). After multivariable adjustment, CPI 3 (odds ratio [OR] 3.594, 95% confidence interval [CI] 1.553–8.316) and CPI 4 (OR 5.837, 95% CI 2.341–14.555) were associated with higher odds of undiagnosed diabetes in men, whereas no significant association was observed in women (p for sex interaction = 0.004). Periodontal status was not associated with undiagnosed prediabetes in either sex. Conclusions: In this cross-sectional analysis, CPI-defined periodontitis was associated with higher odds of undiagnosed diabetes in men. These findings do not establish causality or the diagnostic performance of periodontal examination as a screening test; rather, periodontal findings may help identify individuals in whom standard diabetes risk assessment or medical referral could be considered.

Background: Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are an increasing cause of complicated urinary tract infections (UTIs). Reliance on carbapenems to treat these infections accelerates resistance, underscoring the urgent need for effective oral transition options to preserve last-line agents and lessen healthcare burden. Methods: We conducted a multicenter, open-label, randomized, noninferiority trial at four tertiary hospitals in South Korea (November 2022–June 2025). Adults hospitalized with complicated UTIs due to ESBL-producing Enterobacterales who improved after 3–7 days of intravenous antibiotics were randomized (1:1) to either continue intravenous carbapenem or β-lactam/β-lactamase inhibitor therapy or switch to oral fosfomycin trometamol (3 g once daily). The primary outcome was clinical cure, defined as resolution of urinary tract infection–related symptoms and signs within 4 days after completion of treatment. Secondary outcomes included microbiological cure, readmission, adverse events, and 30-day recurrence. Results: Of the 344 screened patients, 299 were randomized (152 oral fosfomycin; 147 intravenous therapy). Clinical cure occurred in 92.8% of the oral fosfomycin group and 95.2% of the intravenous group (risk difference, −2.47%; 95% CI −7.84 to 2.89), confirming noninferiority. Microbiological cure was similarly high in both groups: urine (98.0% vs 96.6%) and blood (97.3% vs 97.5%). Safety profiles and 30-day outcomes were also comparable. Conclusions: Oral fosfomycin was noninferior to continued intravenous therapy when used as oral transition therapy for complicated UTIs caused by ESBL-producing Enterobacterales. These findings provide evidence to support oral fosfomycin transition as a carbapenem-sparing antibiotic stewardship strategy for patients with complicated UTIs caused by ESBL-producing Enterobacterales. Clinical Trials Registration: KCT0007669.

Background/Objectives: This study analyzes the relationship between obesity phenotypes and sleep apnea risk in the Korean population. Methods: This study utilized data from the Korean National Health and Nutrition Examination Survey (KNHANES) collected between 2019 and 2021 (n = 10,970 adults; age ≥ 40 years). Obesity phenotypes were classified into four groups based on body mass index (BMI) and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). Sleep apnea risk was assessed using the STOP-Bang questionnaire, and multivariate logistic regression analyses were performed to evaluate the association between obesity phenotypes and sleep apnea. Results: Among the 10,970 participants, the phenotypes were as follows: MHNW, 51.1%; MANW, 10.3%; MHO, 15.8%; and MAO, 21.8%. Baseline characteristics differed significantly across phenotypes, with the metabolically unhealthy groups (MANW and MAO) being older and exhibiting more cardiometabolic risk factors than the metabolically healthy groups. The prevalence of STOP-Bang questionnaire components differed significantly across phenotypes (all p < 0.001), and the mean STOP-Bang score increased from MHNW to MAO. In multivariate logistic regression analyses, the odds (adjusted odds ratio [95% CI]) of high sleep apnea risk were significantly elevated in all non-MHNW phenotypes: MAO (10.27 [7.71–13.68]), MHO (6.17 [4.35–8.75]), and MANW (1.91 [1.22–2.98]). Notably, MAO conferred a significantly higher risk than MHO (OR 1.69 [1.34–2.13]), highlighting the synergy of obesity and metabolic dysfunction. Obesity phenotypes, defined by BMI and metabolic health status, were differentially associated with sleep apnea risk in Korean adults. The highest risk was observed in individuals with both obesity and metabolic syndrome, while metabolically abnormal normal-weight adults also showed a significantly increased risk. Conclusions: Metabolic dysfunction may contribute to sleep apnea risk beyond body size alone and may be considered in risk stratification strategies.

Background and Objectives: Hepatic steatosis is associated with an increased risk of liver-related morbidity and mortality. Although numerous studies have reported associations between depression, obesity, metabolic syndrome, and cardiovascular disease, the relationship between depression and hepatic steatosis has not yet been fully elucidated. Moreover, obesity is a shared risk factor for hepatic steatosis and depression; however, few studies have adequately adjusted for obesity as a potential confounder. In this study, we investigated the association between depression and hepatic steatosis stratified by obese and non-obese status. Materials and Methods: This study used data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare between 2010 and 2019, which was a cross-sectional and nationally representative study of non-institutionalized civilians using a stratified, multistage, clustered probability sampling design. Multivariate logistic regression analyses were conducted to evaluate the association between depression and hepatic steatosis in the groups stratified by obese status. Results: Of 80,861 participants, data from 45,307 were included in the analysis. The prevalence of non-obese and obese hepatic steatosis was 3.1% and 19.3%, respectively, and the prevalence of diagnosed depression was 4.6%. Individuals with hepatic steatosis showed less favorable metabolic profiles, including higher rates of diabetes and elevated liver enzyme levels. Those with depression were older, predominantly female, and had lower socioeconomic status. After fully adjusting for confounding factors, multivariate logistic regression analysis showed that non-obese hepatic steatosis was significantly associated with an increased risk of depression, and obese hepatic steatosis was significantly associated with suicidal ideation and attempts. Conclusions: This study suggests a significant association between depression and hepatic steatosis with and without obese status. Given the significant impact of hepatic steatosis on depression outcomes, healthcare providers should screen patients with hepatic steatosis for depression and provide appropriate treatment as needed.

Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors are widely used to manage type 2 diabetes mellitus (T2DM) because of their glucose-lowering and cardioprotective effects. However, euglycemic diabetic ketoacidosis (euDKA) is an uncommon but serious adverse event. EuDKA is characterized by metabolic acidosis and ketosis with only mild-to-moderate hyperglycemia, making diagnosis challenging. The risk of this interaction may be increased with the concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly during periods of reduced caloric intake or the presence of gastrointestinal symptoms. Case: A 38-year-old woman with newly diagnosed T2DM presented with five days of fatigue, poor oral intake, nausea, and vomiting. She had recently initiated semaglutide (GLP-1RA) for weight loss and practiced prolonged intermittent fasting. One week prior, she had started metformin and enavogliflozin, a selective SGLT2 inhibitor. Laboratory results showed a glucose level of 137 mg/dL, urine ketones (+++), lactate level of 4.87 mg/dL, HbA1c of 9.3%, C-peptide of 0.88 ng/mL, and high anion gap metabolic acidosis. She was diagnosed with euDKA and treated with IV fluids, insulin infusion, dextrose, and potassium supplementation. Her symptoms resolved, and she was discharged in a stable condition. Conclusion: This case highlights the importance of recognizing euDKA in patients using SGLT2 inhibitors and GLP-1RAs, particularly those with fasting or gastrointestinal symptoms. Clinicians should suspect euDKA even without significant hyperglycemia to enable prompt diagnosis and management, thereby preventing complications.

The metabolic benefits of sodium-glucose co-transporter 2 inhibitors in clinical application are well established; however, there is dearth of knowledge on their impact on adipokine regulation. This study investigated the effect of enavogliflozin on adiponectin and leptin in patients with type 2 diabetes. This secondary analysis of a phase III randomized, double-blind, placebo-controlled trial evaluated changes in serum adiponectin and leptin over 24 weeks. Analysis of covariance was used with baseline values and weight change as covariates to examine whether the effects of enavogliflozin persisted after adjusting for weight change. Correlations between adipokine changes and key metabolic parameters were also assessed. Over the 24 weeks, the enavogliflozin group showed increased adiponectin levels with a least squares (LS) mean difference of 0.98 mg/L compared with the placebo group, while leptin levels showed a significant decrease with an LS mean difference of −2.99 µg/L. Enavogliflozin significantly reduced leptin levels over 24 weeks after adjusting for weight change; however, adiponectin changes were not significant after adjusting for weight change. Adiponectin levels significantly increased across weight loss categories, but leptin showed no significant differences. Leptin changes over 24 weeks significantly were positively correlated with changes in homeostasis model assessment of insulin resistance and homeostasis model assessment of β-cell function but significantly negatively correlated with changes in serum ketone and urinary glucose-to-creatinine ratio. Enavogliflozin treatment decreased leptin over 24 weeks in patients with type 2 diabetes, and this effect remained significant after adjusting for weight change, suggesting an improved adipokine profile. Reductions in leptin were also associated with improvements in insulin resistance and increases in serum ketone levels. These results highlight enavogliflozin as a potential treatment beyond glycemic control, offering additional benefits in managing metabolic dysregulation associated with type 2 diabetes. Not applicable (post hoc analysis).

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in managing type 2 diabetes mellitus (T2DM) due to their glucose-lowering and cardioprotective effects. However, euglycemic diabetic ketoacidosis (euDKA) is an uncommon but serious adverse event. EuDKA is characterized by metabolic acidosis and ketosis with only mild to moderate hyperglycemia, making diagnosis challenging. Risk may be elevated with concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), especially during reduced caloric intake or gastrointestinal symptoms. Case: A 38-year-old woman with newly diagnosed T2DM presented with five days of fatigue, poor oral intake, nausea, and vomiting. She had recently initiated semaglutide (GLP-1RA) for weight loss and was practicing prolonged intermittent fasting. One week prior, she was started on metformin and enavogliflozin, a selective SGLT2 inhibitor. Laboratory results showed glucose 137 mg/dL, urine ketones (+++), lactate 4.87 mg/dL, HbA1c 9.3%, C-peptide 0.88 ng/mL, and high anion gap metabolic acidosis. She was diagnosed with euDKA and treated with IV fluids, insulin infusion, dextrose, and potassium supplementation. Her symptoms resolved, and she was discharged in stable condition. Conclusion: This case emphasizes the importance of recognizing euDKA in patients using SGLT2 inhibitors and GLP-1RAs, particularly with fasting or gastrointestinal symptoms. Clinicians should suspect euDKA even without significant hyperglycemia, enabling prompt diagnosis and appropriate management to prevent complications.

Background/Objectives: The association between chronic kidney disease (CKD) and body size phenotypes in metabolically diverse but apparently healthy adult populations remains inadequately understood. This study investigated the association between CKD and body size phenotypes in a nationally representative sample of healthy Korean adults. Methods: Data from 8227 participants in the 2019–2021 Korean National Health and Nutrition Examination Survey were analyzed. Participants were categorized into four body size phenotypes by combining BMI status (normal weight or obese) with metabolic health status (healthy or abnormal)—MHNW (Metabolically Healthy Normal Weight), MANW (Metabolically Abnormal Normal Weight), MHO (Metabolically Healthy Obese), or MAO (Metabolically Abnormal Obese). CKD was defined based on the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR). To assess the association between CKD and body size phenotypes, multivariable logistic regression analyses were performed. Results: CKD prevalence was 4.4%. MANW and MAO made up 12.6% and 26.4% of the CKD group, compared to 5.0% and 13.2% of the non-CKD group. CKD prevalence by phenotype was observed as follows: MHNW, 3.2%; MANW, 10.5%; MHO, 4.0%; and MAO, 8.5%. CKD odds were highest in the MAO group (OR: 3.770, 95% CI: 2.648–5.367), followed by the MANW (OR: 2.492, 95% CI: 1.547–4.016) and MHO (OR: 1.974, 95% CI: 1.358–2.870) groups. MAO individuals carried a higher CKD risk than MHO individuals (OR: 1.897, 95% CI: 1.221–2.945). Conclusions: Among apparently healthy adults, body size phenotypes—particularly those with metabolic abnormalities—were significantly associated with the presence of CKD. These findings highlight the need to assess both metabolic health and body composition for effective CKD prevention and management.

Response to Letter in regards to Potential Cardiovascular Risks Associated with Naltrexone-Bupropion Treatment in Overweight Patients [Letter]