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Abstract Low muscle mass is a risk factor for mortality in patients with chronic kidney disease (CKD). However, it is not clear to what extent low muscle mass contributes to this risk, either independently or in combination with metabolic abnormalities and frailty. This study used data from the National Health and Nutrition Examination Survey 1999–2006 and 2011–2018. Low muscle mass was defined as Appendicular Skeletal Mass Index

Abstract Background Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. Methods and results We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate’s beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824–0.998). Conclusions The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.

Background Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. Methods This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. Results Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. Conclusion This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Abstract Background Sarcopenic obesity, defined as the coexistence of low muscle mass and high adiposity, is associated with cardiovascular disease (CVD) and mortality. However, to what extent sarcopenia contributes to these risks independently or in conjunction with other cardiovascular risk factors remains unclear. This study aimed to investigate the association of low muscle mass, central obesity (COB), metabolic abnormalities, and their combinations with CVD and mortality risk. Methods This cross‐sectional analysis used data from the National Health and Nutrition Examination Survey 1999–2006 and 2011–2018. Participants aged >20 years and with reported whole‐body dual X‐ray absorptiometry data were included. Participants were divided into eight groups based on low muscle mass, metabolic abnormalities, and COB status. Results The mean age of participants was 55 years, and 50.4% of participants were male. Low muscle mass was observed in 2472 (14.6%) out of 16 839 participants. Among the eight groups, the metabolically unhealthy COB group with low muscle mass had the highest hazard ratio (HR) for all‐cause mortality (HR, 2.00; 95% CI, 1.56–2.56; P

Background and Objectives: Total knee arthroplasty (TKA) is an effective treatment option for severe knee osteoarthritis. Understanding the impact of diabetes mellitus (DM) on postoperative outcomes is crucial for improving patient satisfaction after TKA. This study aimed to investigate the influence of DM on postoperative complications and mortality after TKA. Materials and Methods: We conducted a systematic review and meta-analysis by searching relevant studies published before December 2023 in the PubMed, EMBASE, Cochrane Library, Medline, and Web of Science databases. The assessment included demographic data, comorbidities, and postoperative complications after primary TKA for both DM and non-DM patients. The odds ratio (OR) was used to represent the estimate of risk of a specific outcome. Results: Thirty-nine studies were finally included in this meta-analysis. Patients with DM had higher rates of periprosthetic joint infection (OR: 1.71, 95% confidence interval [CI]: 1.46–2.00, p < 0.01) and prosthesis revision (OR: 1.37, 95% CI: 1.23–1.52, p < 0.01). Moreover, patients with DM showed an elevated incidence of pneumonia (OR: 1.54, 95% CI: 1.15–2.07, p < 0.01), urinary tract infection (OR: 1.86, 95% CI: 1.07–3.26, p = 0.02), and sepsis (OR: 1.61, 95% CI: 1.46–1.78, p < 0.01). Additionally, the postoperative risk of cardiovascular (OR: 2.49, 95% CI: 1.50–4.17, p < 0.01) and cerebrovascular (OR: 2.38, 95% CI: 1.48–3.81, p < 0.01) events was notably higher in patients with DM. The presence of DM increased the risk of deep vein thrombosis (OR: 1.58, 95% CI: 1.22–2.04, p < 0.01), but did not lead to an increased risk of pulmonary embolism. Most importantly, DM was associated with a higher mortality rate within 30 days after TKA (OR: 1.27, 95% CI: 1.02–1.60, p = 0.03). Conclusions: Patients with DM exhibited a higher rate of postoperative complications after TKA, and DM was associated with a higher mortality rate within 30 days after TKA. It is crucial to educate patients about the perioperative risk and develop evidence-based guidelines to prevent complications after TKA.

BackgroundRecent studies have presented the concept of the obesity paradox, suggesting that individuals with obesity have a lower risk of death than those without obesity. This paradox may arise because body mass index (BMI) alone is insufficient to understand body composition accurately. This study investigated the relationship between fat and muscle mass and the risk of mortality in individuals with overweight/obesity.MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and 2011 to 2018, which were linked to mortality information obtained from the National Death Index. Multiple Cox regression analyses were performed to estimate mortality risk. Subgroup analysis was conducted using propensity score-matched (PSM) data for age, sex, and race/ethnicity.ResultsThis study included 16,555 participants who were overweight/obese (BMI≥25 kg/m2). An increase in appendicular skeletal muscle mass index was associated with a lower mortality risk (hazard ratio [HR]: 0.856; 95% confidence interval [CI]: 0.802–0.915). This finding was consistent with the subgroup analysis of the PSM data. Contrastingly, a high fat mass index was associated with an increased risk of mortality. Sarcopenic overweight/obesity was significantly associated with high mortality compared to obesity without sarcopenia (HR: 1.612, 95%CI: 1.328–1.957). This elevated risk was significant in both age- and sex-based subgroups. This finding was consistent with the subgroup analysis using PSM data.ConclusionIn contrast to the obesity paradox, a simple increase in BMI does not protect against mortality. Instead, low body fat and high muscle mass reduce mortality risk.

Abstract Cigarette smoking is one of the leading causes of preventable and premature death worldwide. Even worse, many people are generally exposed to passive smoking, which leads to several respiratory diseases and related mortalities. Considering, more than 7000 compounds are included in cigarettes, their combustion results intoxicants that have deleterious effects on health. However, there is a lack of research analyzing the effects of smoking and passive smoking on all-cause and disease-specific mortality through its chemical compounds including heavy metals. Thus, this study aimed to evaluate the effect of smoking and passive smoking on all-cause and disease-specific mortality mediated by cadmium, one of the representative smoking-related heavy metals using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 in the United States. We found that current smoking and passive smoking was related to increased risk of all-cause, CVD-related, and cancer-related mortality. Notably, passive smoking showed a synergistic effect with smoking status on the risk of mortality. In particular, current smokers with passive smoking had the highest risk of all-cause and disease-specific deaths. In addition, the accumulation of cadmium in the blood due to smoking and passive smoking mediates the increased risk of all-cause mortality. Further studies are needed to monitor and treat cadmium toxicity to improve smoking-related mortality rates.

Background The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea. Methods Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection. Results Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status. Conclusion Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

Background Thyroid cancer screening has contributed to the skyrocketing prevalence of thyroid cancer. However, the true benefit of thyroid cancer screening is not fully understood. This study aimed to evaluate the impact of screening on the clinical outcomes of thyroid cancer by comparing incidental thyroid cancer (ITC) with non-incidental thyroid cancer (NITC) through a meta-analysis. Methods PubMed and Embase were searched from inception to September 2022. We estimated and compared the prevalence of high-risk features (aggressive histology of thyroid cancer, extrathyroidal extension, metastasis to regional lymph nodes or distant organs, and advanced tumor-node-metastasis [TNM] stage), thyroid cancer-specific death, and recurrence in the ITC and NITC groups. We also calculated pooled risks and 95% confidence intervals (CIs) of the outcomes derived from these two groups. Results From 1,078 studies screened, 14 were included. In comparison to NITC, the ITC group had a lower incidence of aggressive histology (odds ratio [OR], 0.46; 95% CI, 0.31 to 0.7), smaller tumors (mean difference, −7.9 mm; 95% CI, −10.2 to −5.6), lymph node metastasis (OR, 0.64; 95% CI, 0.48 to 0.86), and distant metastasis (OR, 0.42; 95% CI, 0.23 to 0.77). The risks of recurrence and thyroid cancer-specific mortality were also lower in the ITC group (OR, 0.42; 95% CI, 0.25 to 0.71 and OR, 0.46; 95% CI, 0.28 to 0.74) than in the NITC group. Conclusion Our findings provide important evidence of a survival benefit from the early detection of thyroid cancer compared to symptomatic thyroid cancer.

Abstract Background Obesity is associated with an increased risk of developing type 2 diabetes mellitus (T2DM) and end‐stage renal disease (ESRD). This study aimed to examine the effect of waist circumference (WC) on the risk for ESRD based on glycaemic status in a Korean population‐based sample. Methods This cohort study with a 9.2‐year follow‐up period used a population‐based National Health Insurance Service health checkup database with approximately 10 585 852 participants who were followed up from 2009 to the time of ESRD diagnosis. WC was categorized into seven levels in 5‐cm increments, with Level 4 as the reference group. Glycaemic status was categorized into the following groups: normal fasting glucose (NFG), impaired fasting glucose (IFG), newly diagnosed T2DM, T2DM treated with ≤2 oral hypoglycaemic agents (OHAs) and diabetes treated with ≥3 OHAs or insulin. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for ESRD according to WC values and glycaemic status of the participants. Results The study finally included 10 177 245 patients with a mean age of 47.1 (13.8) years. The study population included 5 604 446 men (55.1%) and 4 572 799 women (45.9%). In total, 8.3% (n = 877 143) of the study population had diabetes. During the mean follow‐up of 9.2 (1.0) years (93 554 951 person‐years of follow‐up), 23 031 individuals were newly diagnosed with ESRD. The ESRD risk increased in parallel with an increase in WC in participants without T2DM, that is, the NFG and IFG groups (adjusted HRs [95% CIs] of WC Levels 4, 5 and 6: 1.17 [1.09–1.26], 1.37 [1.25–1.51] and 1.84 [1.63–2.07] in the NFG group and 1.06 [0.97–1.16], 1.23 [1.10–1.38] and 1.80 [1.57–2.06] in the IFG group, respectively). In patients with T2DM, the risk for ESRD was significantly increased in those with a low WC (adjusted HRs [95% CIs] of WC Level 1: 2.23 [1.77–2.80], 3.18 [2.70–3.74] and 10.31 [9.18–11.59] in patients with newly diagnosed diabetes, patients on ≤2 OHAs and those on ≥3 OHAs or insulin, respectively). The association between WC and ESRD thus showed a J‐shaped pattern in patients with newly diagnosed T2DM and a U‐shaped pattern in those on ≤2 OHAs and on ≥3 OHAs or insulin. Conclusions Central obesity substantially increases the risk of developing ESRD regardless of glycaemic status. The harmful effects of low WC only become significant with the progression of T2DM.

Abstract The body mass index (BMI) neither differentiates fat from lean mass nor does it consider adipose tissue distribution. In contrast, the recently introduced z-score of the log-transformed A Body Shape Index (LBSIZ) can be applied to measure obesity using waist circumference (WC), height, and weight. We aimed to investigate the association between LBSIZ and mortality. We used data from the National Health and Nutrition Examination Survey 1999–2014 and linked the primary dataset to death certificate data from the National Death Index with mortality follow-up through December 31, 2015. A multiple Cox regression analysis was performed to evaluate the hazard ratio (HR) of all-cause and cardiovascular disease (CVD) mortalities with adjustment for baseline characteristics. LBSIZ, WC, and BMI showed positive association with total fat percentage (P

Purpose We investigated the relationship between nocturia and mortality risk in the United States. Methods Data were obtained from the National Health and Nutrition Examination Survey 2005–2010. Mortality data were obtained by linking the primary database to death certificate data found in the National Death Index with mortality follow-up up to December 31, 2015. Nocturia was defined based on symptoms reported in the symptom questionnaire. We categorized patients into 2 groups: mild nocturia (2–3 voids/night) and moderate-to severe nocturia (≥4 voids/night). Multiple Cox regression analyses were performed with adjustment for confounding variables at the baseline survey. Results This study included 9,892 adults (4,758 men, 5,134 women). Nocturia occurred in 3,314 individuals (33.5%). Nocturia was significantly associated with all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.10–1.39) and cardiovascular disease (CVD) mortality (HR, 1.55; 95% CI, 1.19–2.01). Moreover, the mortality risk increased with increasing nocturia severity. Further analysis with propensity score matching showed that nocturia was still significantly associated with all-cause mortality and CVD mortality. In subgroup analysis according to sex, nocturia was significantly associated with allcause mortality and CVD mortality in men. In women, moderate-to-severe nocturia was significantly associated with allcause mortality and CVD mortality. In subgroup analysis according to cardio-metabolic diseases, nocturia was associated with CVD mortality in patients with diabetes mellitus, hypertension, dyslipidemia, or CVD at baseline. In subgroup analysis of patients without diabetes mellitus, hypertension or CVD, nocturia was significantly associated with all-cause mortality. Conclusions Nocturia was significantly associated with mortality in men and women after adjusting for major confounding factors.

Background Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

Abstract In this study, we aimed to propose a novel diabetes index for the risk classification based on machine learning techniques with a high accuracy for diabetes mellitus. Upon analyzing their demographic and biochemical data, we classified the 2013–16 Korea National Health and Nutrition Examination Survey (KNHANES), the 2017–18 KNHANES, and the Korean Genome and Epidemiology Study (KoGES), as the derivation, internal validation, and external validation sets, respectively. We constructed a new diabetes index using logistic regression (LR) and calculated the probability of diabetes in the validation sets. We used the area under the receiver operating characteristic curve (AUROC) and Cox regression analysis to measure the performance of the internal and external validation sets, respectively. We constructed a gender-specific diabetes prediction model, having a resultant AUROC of 0.93 and 0.94 for men and women, respectively. Based on this probability, we classified participants into five groups and analyzed cumulative incidence from the KoGES dataset. Group 5 demonstrated significantly worse outcomes than those in other groups. Our novel model for predicting diabetes, based on two large-scale population-based cohort studies, showed high sensitivity and selectivity. Therefore, our diabetes index can be used to classify individuals at high risk of diabetes.

Background Obesity is a chronic disease associated with metabolic diseases such as diabetes and cardiovascular disease. Since the U.S. Food and Drug Administration approved liraglutide as an anti-obesity drug for nondiabetic patients in 2014, it has been widely used for weight control in overweight and obese people. This study aimed to systematically analyze the effects of liraglutide on body weight and other cardiometabolic parameters. Methods We investigated articles from PubMed, EMBASE, and the Cochrane Library to search randomized clinical trials that examined body weight changes with liraglutide treatment. Results We included 31 studies with 8,060 participants for this meta-analysis. The mean difference (MD) between the liraglutide group and the placebo group was −4.19 kg (95% confidence interval [CI], −4.84 to −3.55), with a −4.16% change from the baseline (95% CI, −4.90 to −3.43). Liraglutide treatment correlated with a significantly reduced body mass index (MD: −1.55; 95% CI, −1.76 to −1.34) and waist circumference (MD: −3.11 cm; 95% CI, −3.59 to −2.62) and significantly decreased blood pressure (systolic blood pressure, MD: −2.85 mm Hg; 95% CI, −3.36 to −2.35; diastolic blood pressure, MD: −0.66 mm Hg; 95% CI, −1.02 to −0.30), glycated hemoglobin (MD: −0.40%; 95% CI, −0.49 to −0.31), and low-density lipoprotein cholesterol (MD: −2.91 mg/dL; 95% CI, −5.28 to −0.53; MD: −0.87% change from baseline; 95% CI, −1.17 to −0.56). Conclusion Liraglutide is effective for weight control and can be a promising drug for cardiovascular protection in overweight and obese people.

Background This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes. Methods We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index

Abstract This study aimed to compare the accuracy of novel lipid indices, including the visceral adiposity index (VAI), lipid accumulation product (LAP), triglycerides and glucose (TyG) index, TyG-body mass index (TyG-BMI), and TyG-waist circumference (TyG-WC), in identifying insulin resistance and establish valid cutoff values. This cross-sectional study used the data of 11,378 adults, derived from the United States National Health and Nutrition Examination Survey (1999–2016). Insulin resistance was defined as a homeostasis model assessment-insulin resistance value above the 75th percentile for each sex and race/ethnicities. The area under the curves (AUCs) were as follows: VAI, 0.735; LAP, 0.796; TyG index, 0.723; TyG-BMI, 0.823, and; TyG-WC, 0.822. The AUCs for TyG-BMI and TyG-WC were significantly higher than those for VAI, LAP, and TyG index (vs. TyG-BMI, p

Abstract This study was aimed to evaluate the association between urinary bisphenol A (BPA) levels and risk of obesity in Korean adults. We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012–2014) and Cycle 3 (2015–2017). A total of 10,021 participants aged ≥ 19 years were included. Urine dilution was corrected by the covariate-adjusted standardization (CAS) method. We performed meta-analysis, logistic regression analysis by matching all covariates with a 1:1 propensity score, and a 4-knot restricted cubic spline plot model to calculate the odds ratios (ORs) for obesity according to natural log-transformed BPA levels. Mean urinary BPA concentration was 1.12 µg/L in KoNEHS Cycle 2 and 1.32 µg/L in Cycle 3. BPA levels were significantly higher among obese adults than among non-obese adults in both KoNEHS Cycles 2 and 3. In pooled data of KoNEHS Cycles 2 and 3, BPA showed significant positive associations with ORs for obesity in both sexes, which were more prominent in females (linear) than in males (non-linear). These associations were confirmed in spline analyses. CAS-applied BPA concentrations were positively associated with obesity in nationwide representative samples of Korean adults. Further studies are warranted to confirm and elucidate the underlying mechanism.

Background This study explored the prevalence and clinical characteristics of geriatric syndromes among Korean older adults with diabetes mellitus (DM). Methods We used data from the 2017 National Survey of Older Koreans to analyze the classic geriatric syndromes of polypharmacy, urinary incontinence, falls, cognitive impairment, and functional impairment according to the presence of DM. Results Among 10,299 participants aged 65 years or older, 2,395 had DM. The prevalence of polypharmacy was 64.1% in the DM group and 31.6% in the non-DM group (p

BackgroundEpidemiological studies have suggested an association between selenium (Se) and diabetes mellitus (DM). However, different studies have reported conflicting results. Therefore, we performed a comprehensive meta-analysis to clarify the impact of Se on DM.MethodsWe searched the PubMed database for studies on the association between Se and DM from inception to June 2018.ResultsTwenty articles evaluating 47,930 participants were included in the analysis. The meta-analysis found that high levels of Se were significantly associated with the presence of DM (pooled odds ratios [ORs], 1.88; 95% confidence interval [CI], 1.44 to 2.45). However, significant heterogeneity was found (I2=82%). Subgroup analyses were performed based on the Se measurement methods used in each study. A significant association was found between high Se levels and the presence of DM in the studies that used blood (OR, 2.17; 95% CI, 1.60 to 2.93; I2=77%), diet (OR, 1.61; 95% CI, 1.10 to 2.36; I2=0%), and urine (OR, 1.49; 95% CI, 1.02 to 2.17; I2=0%) as samples to estimate Se levels, but not in studies on nails (OR, 1.24; 95% CI, 0.52 to 2.98; I2=91%). Because of significant heterogeneity in the studies with blood, we conducted a sensitivity analysis and tested the publication bias. The results were consistent after adjustment based on the sensitivity analysis as well as the trim and fill analysis for publication bias.ConclusionThis meta-analysis demonstrates that high levels of Se are associated with the presence of DM. Further prospective and randomized controlled trials are warranted to elucidate the link better.

Purpose We aimed to investigate the association of obesity with nocturia using a nationally representative sample of adults from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2012. Methods A total of 14,135 participants were included in this study. We performed a multivariate logistic regression analysis to find the odds ratio (OR) of obesity for nocturia. Furthermore, the OR of BMI for nocturia was analyzed using restricted cubic splines (RCS) with five knots. We conducted subgroup analysis according to age, sex, hypertension, and diabetes mellitus (DM) and further analysis with 1:1 matching data with propensity score. Results The participants who had body mass index (BMI) above 30 kg/m2 had a significantly higher OR for nocturia (OR, 1.39; 95% CI, 1.28–1.50) than those without obesity. RCS showed a dose-dependent relationship between BMI and OR for nocturia. Subgroup analysis by age, sex, hypertension, and DM showed similar results. Further analysis with 1:1 matching data showed a significant association of obesity with the prevalence of nocturia (OR, 1.25; 95% CI, 1.10–1.41). Conclusions This study reported that obesity was significant association with the prevalence of nocturia with dose-dependent manner, regardless of age, sex, hypertension, and DM after taking major confounding factors into account.

ObjectivePrevious studies on the association between urinary incontinence (UI) and falls have reported conflicting results. We, therefore, aimed to evaluate and clarify this association through a systematic review and meta-analysis of relevant studies.MethodsWe performed a literature search for relevant studies in databases including PubMed and EMBASE from inception up to December 13, 2020, using several search terms related to UI and falls. Based on the data reported in these studies, we calculated the pooled odds ratios (ORs) for falls and the corresponding 95% confidence intervals (CIs) using the Mantel-Haenszel method.ResultsThis meta-analysis included 38 articles and a total of 230,129 participants. UI was significantly associated with falls (OR, 1.62; 95% CI, 1.45-1.83). Subgroup analyses based on the age and sex of the participants revealed a significant association between UI and falls in older (≥65 years) participants (OR, 1.59; 95% CI, 1.31-1.93), and in both men (OR, 1.88; 95% CI, 1.57-2.25) and women (OR, 1.41; 95% CI, 1.29-1.54). Subgroup analysis based on the definition of falls revealed a significant association between UI and falls (≥1 fall event) (OR, 1.61; 95% CI, 1.42-1.82) and recurrent falls (≥2 fall events) (OR, 1.63; 95% CI, 1.49-1.78). According to the UI type, a significant association between UI and falls was observed in patients with urgency UI (OR, 1.76; 95% CI, 1.15-1.70) and those with stress UI (OR, 1.73; 95% CI, 1.39-2.15).ConclusionsThis meta-analysis, which was based on evidence from a review of the published literature, clearly demonstrated that UI is an important risk factor for falls in both general and older populations.

BackgroundThis study aimed to assess the prognostic value of the changes in cardiac arrest rhythms from the prehospital stage to the ED (emergency department) in out-of-hospital cardiac arrest (OHCA) patients without prehospital returns of spontaneous circulation (ROSC).MethodsThis retrospective analysis was performed using nationwide population-based OHCA data from South Korea between 2012 and 2016. Patients with OHCA with medical causes and without prehospital ROSC were included and divided into four groups according to the nature of their cardiac arrest rhythms (shockable or non-shockable) in the prehospital stage and in the ED: (1) the shockable and shockable (Shock-Shock) group, (2) the shockable and non-shockable (Shock-NShock) group, (3) the non-shockable and shockable (NShock-Shock) group, and (4) the non-shockable and non-shockable (NShock-NShock) group. The presence of a shockable rhythm was confirmed based on the delivery of an electrical shock. Propensity score matching and multivariate logistic regression analyses were used to assess the effect of changes in the cardiac rhythms on patient outcomes. The primary outcome was sustained ROSC in the ED; the secondary outcomes were survival to hospital discharge and good neurological outcomes at hospital discharge.ResultsAfter applying the exclusion criteria, 51,060 eligible patients were included in the study (Shock-Shock, 4223; Shock-NShock, 3060; NShock-Shock, 11,509; NShock-NShock, 32,268). The propensity score-matched data were extracted from the six comparative subgroups. For sustained ROSC in the ED, Shock-Shock showed a higher likelihood than Shock-NShock (P ConclusionSustained ROSC in the ED may be expected for patients with shockable rhythms in the ED compared with those with non-shockable rhythms in the ED. For the clinical outcomes, survival to hospital discharge and neurological outcomes, patients with Shock-Shock showed the best outcome, whereas patients with NShock-NShock showed the poorest outcome and Shock-NShock showed a higher likelihood of achieving survival to hospital discharge with no significant differences in the neurological outcomes compared with NShock-Shock.

Background and Objectives: This study analyzed the prognostic impact of mechanical cardiopulmonary resuscitation (CPR) devices in out-of-hospital cardiac arrest (OHCA) patients, in comparison to manual CPR. Materials and Methods: This study was a nationwide population-based observational study in South Korea. Data were retrospectively collected from 142,905 OHCA patients using the South Korean Out-of-Hospital Cardiac Arrest Surveillance database. We included adult OHCA patients who received manual or mechanical CPR in the emergency room. The primary outcome was survival at discharge and the secondary outcome was sustained return of spontaneous circulation (ROSC). Statistical analysis included propensity score matching and multivariate logistic regression. Results: A total of 19,045 manual CPR and 1125 mechanical CPR cases (671 AutoPulseTM vs. 305 ThumperTM vs. 149 LUCASTM) were included. In the matched multivariate analyses, all mechanical CPR devices were associated with a lower ROSC than that of manual CPR. AutoPulseTM was associated with lower survival in the multivariate analysis after matching (aOR with 95% CI: 0.57 (0.33–0.96)), but the other mechanical CPR devices were associated with similar survival to discharge as that of manual CPR. Witnessed arrest was commonly associated with high ROSC, but the use of mechanical CPR devices and cardiac origin arrest were associated with low ROSC. Only target temperature management was the common predictor for high survival. Conclusions: The mechanical CPR devices largely led to similar survival to discharge as that of manual CPR in OHCA patients; however, the in-hospital use of the AutoPulseTM device for mechanical CPR may significantly lower survival compared to manual CPR.

Background: The risk factors of nocturia in older adults remain unclear. We aimed to investigate factors associated with nocturia using the National Health and Nutrition Examination Survey (NHANES) data. Methods: Among 40,790 participants, 4,698 participants aged ≥65 years were included from the NHANES dataset between 2005 and 2012. A multivariate logistic regression analysis was performed to determine the odds ratio (OR) for nocturia. A subgroup analysis was conducted based on sex and underlying diseases. Results: In the multivariate logistic regression model, obesity (OR, 1.46; 95% confidence interval [CI], 1.28–1.68), hypertension (OR, 1.28; 95% CI, 1.07–1.52), and diabetes mellitus (DM) (OR, 1.27; 95% CI, 1.11–1.45) were significantly associated with nocturia. These factors were associated with nocturia regardless of sex. In a subgroup of participants with hypertension, obesity (OR, 1.44; 95% CI, 1.25–1.67) and DM (OR, 1.26; 95% CI, 1.09–1.45) were associated with nocturia. In the additional analysis on patients with DM, nocturia was associated with obesity (OR, 1.33; 95% CI, 1.06–1.67) and duration of DM (OR, 1.02; 95% CI, 1.01–1.03). Conclusion: This study demonstrated that hypertension, DM, and obesity were significantly associated with the prevalence of nocturia in older adult patients regardless of sex. In particular, obesity was associated with nocturia in every subgroup analysis.

BackgroundEpidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC.MethodsWe searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins I2 statistic was used to test for heterogeneity.ResultsThe meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61).ConclusionIn this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

Background: We aimed at evaluating the effect of the z-score of the log-transformed A Body Shape Index (LBSIZ) on cardiovascular disease (CVD) outcomes according to obesity phenotype. Methods: Data were collected from the Korea National Health and Nutrition Examination Survey conducted from 2007 to 2010. Obesity was defined as a body mass index above 25 kg/m² and metabolic abnormality was defined as the presence of two or more metabolic risk factors of the Adult Treatment Panel III definition. The participants were classified by obesity and metabolic healthy status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Each group was further classified into three groups based on the tertile of LBSIZ. A multivariate logistic regression analysis with adjustment for age, sex, smoking status, income, education level, physical activities, alcohol, and energy intake was conducted to evaluate the odds ratio (OR) for CVD events. Results: In the multivariate logistic regression model, MHO participants who are within the third tertile of LBSIZ had a significantly higher OR for CVD events, whereas those who are within the first and second tertile of LBSIZ were not at high risk of developing CVDs compared to MHNO participants who are within the first tertile of LBSIZ. In addition, a similar increase in the OR was observed in MUNO or MUO participants. Conclusion: LBSIZ had the lowest risk for CVDs in the first tertile of LBSIZ and a linear relationship with all its tertiles in MHO, MUNO, and MUO participants.

BackgroundAfter initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.MethodsTotal 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.ResultsIn patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.ConclusionTherefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart. The present meta-analysis was conducted to assess the efficacy and safety of IDegAsp compared with a conventional premixed insulin or basal insulin. We extracted data from citation databases, including PubMed, EMBASE, and the Cochrane Library, since inception to 2021. We calculated the mean differences for hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), self-measured mean glucose, and postprandial glucose (PPG) and odds ratios for confirmed hypoglycemia events. Compared with twice-daily conventional premixed insulin, twice-daily IDegAsp showed a similar effect on changes in HbA1c, but it significantly reduced FPG and self-measured mean glucose levels. Furthermore, compared to once-daily basal insulin, once-daily IDegAsp had a similar effect on changes in HbA1c, but it significantly reduced self-measured mean glucose and PPG levels. The risk of overall confirmed hypoglycemia was similar between treatments; however, the risk of nocturnal hypoglycemia events was significantly lower with IDegAsp than with conventional premixed insulin and basal insulin. Thus, IDegAsp was more effective than conventional premixed insulin and basal insulin at reducing blood glucose with fewer nocturnal hypoglycemia events.

Background and objectiveSarcopenic obesity is associated with a higher risk of cardiometabolic disease and mortality than either sarcopenia or obesity alone. However, no study has investigated body shape indices for the assessment of sarcopenia in obese populations. Thus, this study aimed to evaluate the accuracy of body shape indices to assess sarcopenia in nationally representative populations with abdominal obesity.MethodsData from the U.S. National Health and Nutrition Examination Survey (U.S. NHANES) 1999-2006 and Korea NHANES (KNHANES) 2008-2011 were assessed. The association between Body Shape Index and sarcopenia was analyzed using a receiver operating characteristic curve. The Z-score of the log-transformed A Body Shape Index (LBSIZ) cut-off value was defined as that with the highest score of the Youden's index. Changes in odds ratios (OR) for sarcopenia were investigated using restricted cubic spline (RCS) plots.ResultsThis study included 8,013 American and 4,859 Korean adults with abdominal obesity. The overall area under the curve (AUC) of LBSIZ for sarcopenia was 0.816 (95% CI: 0.794-0.838) in U.S. NHANES and 0.822 (95% CI: 0.799-0.844) in KNHANES, which was higher than that of the body roundness index, conicity index, and waist to height ratio (p with DeLong's test ConclusionThe increased LBSIZ could function as a reliable and cost-effective screening tool for assessing low muscle mass in populations with abdominal obesity.

Background/aimProlonged maintenance of central venous catheters, including peripherally inserted central catheters (PICCs), is a major risk factor for central line-associated bloodstream infection (CLABSI). This study was conducted to evaluate the appropriate duration of PICC maintenance to prevent CLABSI.MethodsA single-center retrospective study was conducted at an 824-bed tertiary hospital in Korea between January 2010 and December 2017. All hospitalized patients who underwent ultrasound-guided PICC insertion were enrolled. CLABSI was diagnosed according to the definitions of the National Health Safety Network. CLABSI caused by PICC was defined as PICC-associated bloodstream infection (PABSI). To identifying statistical correlations between catheter days and PABSI, the odds ratio for PABSI on the basis of the continuous value of catheter days was analyzed using restricted cubic spline splits with five knots. The optimal cut-off value for catheter days was identified by maximizing the area under the receiver operating characteristic (ROC) curve (AUC).ResultsA total of 1,053 patients underwent ultrasound-guided PICC insertion during the study period. Among them, 36 were confirmed as having a PABSI (3.5%, 36/1014; 1.14 per 1000 catheter days). In the restricted cubic spline regression, catheter days showed a dose-dependent relationship with the risk of PABSI. The AUC of the ROC curve for developing a PABSI according to the duration of catheter maintenance was 0.715 (95% CI, 0.639-0.790); the calculated optimal cut-off value was 25 days.ConclusionThe incidence of PABSI was 1.14 per 1000 catheter days and the optimal cut-off value of catheter days to avoid a PABSI was 25 days.

OBJECTIVE:The current methods available for determining insulin resistance are complicated; hence, they are only applicable to small-scale studies. Therefore, this study aimed to classify the characteristics of surrogate measures for insulin resistance and establish valid cut-off values for predicting the development of type 2 diabetes mellitus (DM) in Korean populations. METHODS:This prospective study included 7,643 participants aged 40-69 years from the Ansung-Ansan cohort database (2001-2012). Four surrogate measures, namely homeostasis model assessment-insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), and triglycerides and glucose (TyG) index, were analyzed. We analyzed each measure using receiver operating characteristic (ROC) curve for the development of type 2 DM. The cut-off value was determined as the value with the highest Youden index score in the specificity dominant area. RESULTS:The area under the curve (AUC) was 0.566 (95% confidence interval [CI], 0.548-0.583) for HOMA-IR, 0.622 (95% CI, 0.605-0.639) for VAI, 0.642 (95% CI, 0.625-0.658) for LAP, and 0.672 (95% CI, 0.656-0.687) for TyG index. The AUC of TyG index was significantly higher than that of HOMA-IR, VAI, and LAP (p < 0.001). The cut-off value was 2.54 (sensitivity 36.8%; specificity 73.1%; hazard ratio [HR], 1.41, 95% CI, 1.25-1.59) for HOMA-IR, 2.54 (sensitivity 50.4%; specificity 68.8%; HR, 1.75, 95% CI, 1.55-1.96) for VAI, 36.6 (sensitivity 59.2%; specificity 63.9%; HR, 1.87, 95% CI, 1.64-2.14) for LAP, and 4.69 (sensitivity 62.1%; specificity 63.1%; HR, 2.17, 95% CI, 1.92-2.45) for TyG index. CONCLUSIONS:The TyG index was a better predictor for DM than HOMA-IR. VAI and LAP showed the modest predictability for DM. The TyG index could be a useful supplementary method for identifying individuals at risk for insulin resistance and DM development.

OBJECTIVE:Many people are exposed to perfluoroalkyl substances (PFASs) because these substances are widely used as industrial products. Although epidemiological studies suggest that PFASs can disrupt thyroid hormones, the association between PFAS exposure and thyroid function remains inconclusive. Therefore, we performed a comprehensive meta-analysis to investigate the association between PFASs exposure and thyroid hormones. METHODS:We searched medical literature databases for articles on the association between PFASs-perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS)-and thyroid hormone levels in adults. Twelve articles were included in the meta-analysis, and the pooled z values were calculated with correlation or regression coefficients. RESULTS:The blood PFOS concentration was positively correlated with free T4. The pooled z value was 0.05 (95% confidence interval (CI): 0.03, 0.08). PFOS was negatively correlated with total T4 and total T3 when excluding outlier studies. In a subgroup analysis stratified by mean PFOS concentration, PFOS was observed to be positively associated with free T4 and TSH and negatively associated with total T3 in the intermediate concentration group (8-16 ng/mL). PFOA concentration was negatively correlated with total T4 (z value, -0.06; 95% CI: -0.09, -0.03) after omitting one outlier study. PFHxS also showed a negative correlation with total T4 (z value, -0.04; 95% CI: -0.07, -0.01). A subgroup analysis of pregnant women showed that there was no association between PFASs and thyroid hormones. CONCLUSIONS:Our meta-analysis suggests that PFASs are negatively associated with total T4, and their effect can be different depending on the PFAS concentration.

BACKGROUND:In 2009, a nationwide sentinel surveillance for hand-foot-mouth disease (HFMD) and herpangina (HA) with neurologic complications was initiated in South Korea. We used this surveillance system to investigate the clinical characteristics of patients with either HFMD or HA with neurologic complications, with the aim of determining risk factors for severe neurologic complications. METHODS:A retrospective review of medical records was conducted on all cases of HFMD and HA with neurologic complications that were reported in the national system between April 1, 2009 and December 31, 2014. A severe case was defined as having HFMD or HA with encephalitis, polio-like syndrome, or cardiopulmonary failure, and less-severe cases were defined as having HFMD or HA with aseptic meningitis. RESULTS:A total of 138 cases (less-severe: 90/138, 65.2%; severe: 48/138, 24.8%) were included from 28 hospitals; 28 ineligible cases were excluded. Of 48 severe cases, 27 (56.2%) had encephalitis; 14 (29.2%) had polio-like syndrome; and seven (14.6%) had cardiopulmonary syndrome. The median patient age was 36 months (IQR: 18-60) and 63 (45.7%) patients were female. Most patients completely recovered, except for seven cases that were fatal or resulted in long-term symptoms (5.1%, 3 patients with neurologic sequelae and 4 deaths). In a multivariable logistic regression analysis, lethargy (OR = 4.67, 95% CI: 1.37-15.96, P = 0.014), female sex (OR = 3.51, 95% CI: 1.17-10.50, P = 0.025), and enterovirus A71 (OR = 3.55, 95% CI: 1.09-11.57, P = 0.035) were significantly associated with severe neurologic complications in HFMD and HA patients. CONCLUSION:In patients with HFMD and HA, lethargy, female, and enterovirus A71 may predict severe neurologic complications.

The metabolic outcomes of metabolically healthy obesity (MHO) remain controversial. The aim of the present study was to determine the effect of physical activity on the cardiovascular disease (CVD) outcomes of MHO. The study included participants who were followed for 10 years and recruited from the Korean Genome and Epidemiology Study (KoGES), a population-based cohort study. Participants with previously recorded CVDs or cancer, or who had received steroids or anticoagulants at baseline were excluded. A total of 8144 participants (3,942 men and 4,202 women) fulfilled inclusion criteria. In a multivariate Cox regression model adjusted for age and sex, MHO participants were not at elevated risk of CVD compared with their metabolically healthy non-obese (MHNO) counterparts (HR, 1.28; 95% CI, 0.96-1.71), although both the non-obese (HR, 1.50; 95% CI, 1.19-1.90) and obese (HR, 1.85; 95% CI, 1.48-2.30) participants with metabolic abnormalities were at elevated risk. However, in the subgroup analysis by physical activity, physically inactive MHO participants had a significantly higher HR for CVD events compared to active MHNO participants (HR, 1.54; 95% CI, 1.03-2.30), while active MHO participants were not at elevated risk (HR, 1.15; 95% CI, 0.70-1.89). Physically inactive MHO participants had significantly increased risk of CVD compared to physically active MHNO participants whereas physically active MHO participants did not.

Increased glycemic exposure, even below the diagnostic criteria for diabetes mellitus, is crucial in the pathogenesis of diabetic microvascular complications represented by microalbuminuria. Nonetheless, there is limited evidence regarding which single nucleotide polymorphisms (SNPs) are associated with prediabetes and whether genetic predisposition to prediabetes is related to microalbuminuria, especially in the general population. Our objective was to answer these questions. We conducted a genomewide association study (GWAS) separately on two population-based cohorts, Ansung and Ansan, in the Korean Genome and Epidemiology Study (KoGES). The initial GWAS was carried out on the Ansung cohort, followed by a replication study on the Ansan cohort. A total of 5682 native Korean participants without a significant medical illness were classified into either control group (n = 3153) or prediabetic group (n = 2529). In the GWAS, we identified two susceptibility loci associated with prediabetes, one at 17p15.3-p15.1 in the GCK gene and another at 7p15.1 in YKT6. When variations in GCK and YKT6 were used as a model of prediabetes, this genetically determined prediabetes increased microalbuminuria. Multiple logistic regression analyses revealed that fasting glucose concentration in plasma and SNP rs2908289 in GCK were associated with microalbuminuria, and adjustment for age, gender, smoking history, systolic blood pressure, waist circumference, and serum triglyceride levels did not attenuate this association. Our results suggest that prediabetes and the associated SNPs may predispose to microalbuminuria before the diagnosis of diabetes mellitus. Further studies are needed to explore the details of the physiological and molecular mechanisms underlying this genetic association.

Background: An increased prevalence of depression has been reported in patients with acromegaly. However, most studies included a relatively small sample size owing to the rarity of acromegaly. We aimed to investigate the risk of depression in patients with acromegaly using the Korean National Health Information Database (NHID). Methods: The data of patients with acromegaly in 2006-2016 were collected from the rare incurable disease registry of the NHID. Patients with acromegaly were matched with control participants without acromegaly for age and sex in a 1:5 ratio. Results: Patients who did not receive treatment for acromegaly had a significantly increased risk of depression (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.12-1.82). However, the risk of depression did not increase in patients who received treatment for acromegaly. The multiple Cox regression analysis showed that the risk of depression was significantly higher in the untreated group than in the control group during the first 3 years of observation (HR: 1.829, 95% CI: 1.305-2.563). However, after a time lag of over 3 years, the risk of depression decreased in the untreated group, which is similar to that in the control group. Conclusion: Our nationwide study suggests that patients who did not receive treatment for acromegaly have a higher risk of depression compared with controls. The untreated acromegaly patients should be monitored for the development of depression, especially in the early years after diagnosis. These results could serve as a basis for developing screening strategies to mitigate depression in acromegaly patients. [ABSTRACT FROM AUTHOR]