Genome-wide association of individual vulnerability with alcohol-associated liver disease: A Korean genome and epidemiology study.

BACKGROUND AND AIMS: The quantity of alcohol leading to alcohol-associated liver disease (ALD) varies individually. Genetic backgrounds contributing to the divergence in individual susceptibility to alcohol-induced liver damage have not been elucidated in detail. APPROACH AND RESULTS: Based on the Korean Genome and Epidemiology Study Health Examination (KoGES_HEXA) cohort data, 21,919 participants (40-79 years old) were included and divided into cases and controls based on the ALD diagnostic criteria proposed by the American College of Gastroenterology. Data generated by a genome wide-association study were analyzed using logistic regression to assess the risk of ALD development in nondrinkers, light drinkers, and heavy drinkers. We detected three loci, gamma-glutamyltransferase 1 (GGT1), zinc protein finger 827 (ZNF827) and HNF1 homeobox A (HNF1A), which were significantly associated with ALD risk. The GGT1 rs2006227 minor allele was strongly associated with all groups. Among the minor alleles of single nucleotide polymorphisms (SNPs) in HNF1A, rs1183910 had the strongest association with a protective effect from ALD in light drinkers. However, this association was not observed in heavy drinkers. Five SNPs on chromosome 11 showed suggestive significance in protective effects against ALD. CONCLUSIONS: SNPs, including HNF1A rs1183910 minor allele, are the most promising genetic candidates for protection against ALD. The expression of genes contributing to ALD development may be altered by the amount of alcohol consumed.

Discordance in Secular Trends of Bone Mineral Density Measurements in Different Ages of Postmenopausal Women.

BACKGROUND: Age-adjusted bone mineral density (BMD) in postmenopausal women decreases in developed countries whereas incidence of osteoporotic fracture decreases or remains stable. We investigated secular trends of bone density from 2008 to 2017 among different age groups of postmenopausal women. METHODS: We analyzed BMD data obtained from health check-ups of 4,905 postmenopausal women during three survey cycles from 2008 to 2017. We divided them into 3 groups by age (50-59 years, 60-69 years, and 70 years or more) and observed the transition of lumbar and femoral BMD in each group, before and after adjusting for variables that may affect BMD. RESULTS: Age-adjusted BMD, bone mineral content (BMC), and T-score demonstrated a declining trend over the survey period at lumbar spine (-2.8%), femur neck (-3.5%) and total femur (-4.3%), respectively. In the analysis for the age groups, the BMD, BMC, and T-score presented linear declining trend (-6.1%) in younger postmenopausal women while women aged over 70 or more showed linear increasing trends (+6.3%) at lumbar spine during the survey period. Femoral neck and total femur BMD demonstrated a declining linear trend only in the 50-59 and 60-69 years groups (-5.5%, -5.2%, respectively), but not in the 70 years or more group. CONCLUSION: BMD in younger postmenopausal women has decreased considerably but has increased or plateaued in elderly women. This discordance of BMD trends among different age groups may contribute to decreased incidence of osteoporotic fracture despite a recent declining BMD trend in postmenopausal women.

Serum leptin level and incidence of CKD: a longitudinal study of adult enrolled in the Korean genome and epidemiology study(KoGES).

BACKGROUND: Chronic kidney disease(CKD) is a major public health issue and is highly prevalent in the general population. Leptin is an adipose tissue-derived endocrine factor that has been associated with several metabolic factors involved in cardiovascular diseases. Several studies have investigated the association between leptin and renal diseases so far. But the results are conflicting between the studies. The objective of our study was to verify the direct association of serum leptin level with CKD development. METHODS: This prospective cohort study included 2646 adult aged 40-70 without CKD in the Korean Genome and Epidemiology Study(KoGES) across South Korea from November 2005 to February 2012. The primary outcome was the development of CKD as defined by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Multivariate stepwise logistic regression analysis was done to assess the independent associations, for with the incident of CKD as the dependent variable, in tertiles of leptin values. RESULTS: Among 1100 men and 1546 women with 2.8 mean years of follow-up, incidence of CKD was 18(1.63%) for men and 50(3.23%) for women. In the multivariate logistic regression models, individuals in the highest serum leptin tertile showed significant associations with risk of CKD after adjustment compared to the lowest tertiles in the population. The crude odds ratio for trend was 2.95(p = 0.004) for men. After adjusting for age, baseline eGFR variables showed correlation with statistical significance (OR for trend = 2.25, p = 0.037) for men. The same trends were also seen observed in all population and women also, but no statistical significance was found. CONCLUSIONS: Higher plasma leptin levels are associated with the incidence of CKD, independent of traditional factors such as age, baseline eGFR. Our results suggest that leptin may partly explain part of the reported association between obesity and kidney disease.

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study.

Although many genome-wide association studies (GWASs) have evaluated the association with metabolic disorders, the current study is the first attempt to analyze the genetic risk factors for various metabolic disorders according to sex and age groups of the life course in Korean adults. A total population of 50,808 people were included in this GWAS. The genetic traits for eight metabolic phenotypes were investigated in peri-, and postmenopausal women compared to a younger group or men of corresponding age groups. The metabolic phenotypes include general obesity, abdominal obesity, hypertension, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, and metabolic syndrome. In the total participants, GWAS results for eight metabolic phenotypes found 101 significant loci. Of these, 15 loci were the first reported to be associated with the risk of metabolic disorder. Interestingly, some of the significant loci presented the association with the various phenotypes, which presented when there was a correlation between phenotypes. In addition, we analyzed divided by gender and age (young adult, peri-menopausal group, older adult), and specifically identified specific loci in peri-menopausal women. Meanwhile, several genetic factors associated with metabolic disorders were newly reported in our study. In particular, several genes were significantly associated with one of the metabolic phenotypes in only a single specific group. These findings suggest that menopausal transition rather than aging itself potentiates the influence of genetic risks on metabolic disorders. In addition, some genetic loci with low frequencies may play a role in the metabolic disturbances in a specific sex and age group. The genetic traits derived from our study may contribute to understanding the genetic risk factors for metabolic disorders in the Korean population.

Black rice with giant embryo ameliorates serum C-reactive protein in adults with metabolic syndrome.

Metabolic syndrome is well known to increase the risk of cardiovascular diseases. We have reported that phytochemicals rich black rice with giant embryo reduced fat mass and metabolic disorders in an animal model. However, such effects have not been evaluated in humans. Subjects with metabolic syndrome (n = 49, 38 male, 44.3 ± 6.1 years) were randomly assigned into two groups and ingested roasted black-rice with giant embryo (BR, n = 26, 20 male) or white-rice (WR, n = 23, 18 male) powders mixed with water for breakfast for three months. Subjects were evaluated for various metabolic parameters before and after intervention. All parameters were not significantly different between groups before starting the intervention. After three months of consumption of either BR or WR, changes of body weight in BR vs WR groups (-1.54 kg vs -1.29 kg, p = 0.649) as well as waist circumference (-1.63 cm vs -1.02 cm, p = 0.365) were not significantly different between groups. However, changes in highly-sensitive C reactive proteins in BR vs WR groups (-0.110 mg/dl vs 0.017 mg/dl, p = 0.003) had significant differences. Three months of meal replacement with BR had a significant reduction of highly-sensitive C reactive protein compared to those with WR in adults with metabolic syndrome.

Effect of the potent CYP2D6 inhibitor sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy male Korean volunteers.

1. Recently, we demonstrated that sarpogrelate is a potent and selective CYP2D6 inhibitor in vitro. Here, we evaluated the effect of sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy subjects. 2. Nine healthy male subjects genotyped for CYP2D6*1/*1 or *1/*2 were included in an open-label, randomized, three treatment-period and crossover study. A single oral dose of metoprolol (100 mg) was administered with water (treatment A) and sarpogrelate (100 mg bid.; a total dose of 200 mg and treatment B), or after pretreatment of sarpogrelate for three days (100 mg tid.; treatment C). Plasma levels of metoprolol and α-hydroxymetoprolol were determined using a validated LC-MS/MS method. Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol. 3. Metoprolol was well tolerated in the three treatment groups. In treatment B and C groups, the AUCt of metoprolol increased by 53% (GMR, 1.53; 90% CI, 1.17-2.31) and by 51% (1.51; 1.17-2.31), respectively. Similar patterns were observed for the increase in Cmax of metoprolol by sarpogrelate. However, the pharmacodynamics of metoprolol did not differ significantly among the three treatment groups. 4. Greater systemic exposure to metoprolol after co-administration or pretreatment with sarpogrelate did not result in clinically relevant effects. Co-administration of both agents is well tolerated and can be employed without the need for dose adjustments.

Selective inhibition of cytochrome P450 2D6 by Sarpogrelate and its active metabolite, M-1, in human liver microsomes.

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC50 (Ki) value of 3.05 µM (1.24 µM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC50 (Ki) value of 0.201 µM (0.120 µM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (Ki, 0.129 µM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 1'-hydroxylation and metoprolol α-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions.

Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Data on the benefits of the once weekly GLP-1 receptor agonist semaglutide 2·4 mg for weight management in people from east Asia are insufficient. The objective of this study was to determine the efficacy and safety of once weekly semaglutide 2·4 mg versus placebo for weight management in a predominantly east Asian adult population. METHODS: This randomised phase 3a, double-blind multicentre controlled trial (STEP 7) recruited participants from 23 hospitals and trial centres in China, Hong Kong, Brazil, and South Korea. Adults with overweight or obesity, with or without type 2 diabetes, were randomly assigned (2:1) to receive a subcutaneous injection of either semaglutide 2·4 mg or placebo once a week for 44 weeks, plus a diet and physical activity intervention. Randomisation was done in blocks of six with an interactive web response system and was stratified by diagnosis of type 2 diabetes. Participants, investigators, and the trial sponsor were masked to treatment allocation until after database lock. Primary endpoints were percentage change in mean bodyweight and proportion of participants having reached a weight reduction of at least 5% of bodyweight from baseline to week 44. Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04251156, and is now complete. FINDINGS: From Dec 8, 2020, to Aug 23, 2022, 448 participants were screened, of whom 375 were randomly assigned to either the semaglutide 2·4 mg group (n=249) or the placebo group (n=126). Estimated mean percentage change in bodyweight from baseline to week 44 was -12·1% (SE 0·5) with semaglutide 2·4 mg versus -3·6% (0·7) with placebo (estimated treatment difference -8·5 percentage points [95% CI -10·2 to -6·8]; p<0·0001). At week 44, the proportion of participants who lost 5% or more of their bodyweight was higher in the semaglutide 2·4 mg group than in the placebo group (203/238 [85%] vs 36/116 [31%]); odds ratio 13·1 (95% CI 7·4-23·1; p<0·0001). Adverse events were reported by 231 (93%) of 249 participants in the semaglutide 2·4 mg group and 108 (86%) of 126 participants in the placebo group, the most common of which were gastrointestinal disorders (168/249, 67% vs 45/126, 36%). INTERPRETATION: The results of this study support the use of semaglutide 2·4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Mandarin, Portuguese and South Korean translations of the abstract see Supplementary Materials section.

Methane Gas in Breath Test is Associated with Non-Alcoholic Fatty Liver Disease.

Although the association between Body Mass Index (BMI) level and metabolic diseases as well as the association between the breath test results and BMI level have been studied, their relationship between breath hydrogen/methane level and metabolic diseases need to be further clarified. This study aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders and their key risk factors. An elevated BMI level significantly increases the risk of developing metabolic disease; it was included in this study to find their association. Diabetes mellitus, dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD) are metabolic diseases included in this study. An analysis was performed on the medical records including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. Subjects were grouped according to four different criteria of the LBT hydrogen and methane level: 1) Normal (N) (Hydrogen < 20 ppm and Methane < 3 ppm); 2) Hydrogen only (H+) (Hydrogen ≥ 20 ppm and Methane < 3 ppm); 3) Methane positive (M+) (Hydrogen < 20 ppm and Methane ≥ 3 ppm); and 4) Methane and hydrogen positive (M+/H+) (Hydrogen ≥ 20 ppm and Methane ≥ 3 ppm). Of 441 subjects, 325 (72.1%) had positive results for methane only (M+). BMI and prevalence of NAFLD were higher in subjects with M+ than in subjects with hydrogen and methane positivity (H+/M+). According to multivariate analysis, the odds ratio (OR) of M+ was 2.002 (with 95% CI: 1.244-3.221, P = 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas in breath tests has the potential to be an easily measurable biomarker for the diagnosis of NAFLD. .

Obesity in Children and Adolescents: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity.

Hair calcium concentration is associated with calcium intake and bone mineral density.

Calcium concentration in hair, representing intracellular calcium levels, is associated with systemic diseases such as coronary artery disease. To date, there are no previous studies which investigate the regulation of hair calcium levels. The aim of the study is to investigate whether hair calcium concentration is related to calcium intake and calcium content in bone - bone mineral density (BMD). An observational research study was conducted with 55 women over the age of 20 who visited a university hospital in Suwon, Korea. The average age of the women was 51.45. Depending on the concentration of hair calcium, participants were divided into quartiles to compare calcium intake and BMD. There was no difference in demographic, anthropometric, and biochemical characteristics between the highest quartile of hair calcium concentration and the rest of the quartiles. However, the highest quartile ingested significantly less calcium compared to the rest of the quartiles (p < 0.05). The highest quartile of hair calcium concentration also showed significantly lower BMD and T-score in the L1 - 4 vertebrae compared to the rest of the quartiles (p < 0.05). These results show that high hair calcium concentration was associated with low calcium intake and low BMD.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis.

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10-7 (odds ratio = 1.72) and 1.1 × 10-7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

Erosive esophagitis may be related to small intestinal bacterial overgrowth.

OBJECTIVES: Erosive esophagitis (EE) may be related to small intestinal bacterial overgrowth (SIBO) because gastro-esophageal reflux disease has been a comorbid condition of irritable bowel syndrome (IBS), which has been associated with SIBO. We conducted a pilot study to investigate whether EE was associated with SIBO. MATERIAL AND METHODS: Twenty-eight patients with EE according to the Los Angeles classification criteria and 29 sex- and age-matched subjects without EE were enrolled. All subjects underwent esophagogastroduodenoscopy and a lactulose hydrogen breath test. A peak of H2 values >20 ppm above the basal value after 10 g of lactulose ingestion was considered abnormal and suggestive of SIBO. RESULTS: Abnormal lactulose hydrogen breath test results were found in 67% of EE patients, as compared with 37% in the control group; the difference was statistically significant (p = 0.024). Among the subjects without IBS, subjects with EE and controls had 65% and 31% abnormal lactulose hydrogen breath test results, respectively; the difference was also statistically significant (p = 0.032). CONCLUSIONS: Subjects with EE had a higher prevalence of SIBO, as assessed by the lactulose hydrogen breath test, with respect to a control group. These findings may suggest that EE is associated with SIBO.

Stress-responsive hypothalamic-nucleus accumbens regulation may vary depending on stressors.

This study was conducted to determine if the stress-responsive hypothalamic-nucleus accumbens (NAc) regulation is a stressor specific event. Male SD rats were subjected to restraint or cold stress for 2 h, and then mRNA expression of corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) was examined by in situ hybridization and the plasma corticosterone levels by radioimmunoassay. Neuronal activations in the PVN and the NAc were examined by c-Fos immunohistochemistry and the brain GABA contents by HPLC. Both restraint and cold stresses increased c-Fos expression in the PVN and the plasma corticosterone; however, CRH expression in PVN was increased only by restraint, but not by cold, stress. Restraint stress significantly increased the NAc neuronal activation, but cold stress failed to do so. Restraint stress increased the NAc-GABA contents and cold stress did the hypothalamic GABA. Results suggest that the HPA axis regulation responding to restraint stress, but not cold stress, may involve the NAc neuronal activation in relation with GABAergic neurotransmission. Additionally, CRH expression in the PVN may not play a major role in the elevation of plasma corticosterone responding to cold stress.

Calcium Supplementation, Risk of Cardiovascular Diseases, and Mortality: A Real-World Study of the Korean National Health Insurance Service Data.

Few studies have investigated the effects of calcium supplementation on cardiovascular outcomes in individuals with low calcium intake in real-world settings. This study examined the association between calcium supplementation and cardiovascular outcomes in the Korean population in a real-world setting. This large retrospective cohort study included patients aged ≥45 years first prescribed calcium supplements in 2010. Age- and sex-matched controls were recruited among those who had no prescription for calcium supplements. Longitudinal data were collected on 31 December 2018. Kaplan−Meier estimation and Cox proportional hazard regression analysis were performed. The cumulative incidence of acute myocardial infarction, ischemic stroke, and death was significantly higher in the calcium supplementation group than in the control group (p < 0.05 by log-rank test). The calcium supplementation group had a significantly higher risk of myocardial infarction, ischemic stroke, and death than the control group. Compared to the control group, the hazard ratios (95% confidence intervals) of the incidence of myocardial infarction, stroke, and death in the supplementation group were 1.14 (1.03−1.27), 1.12 (1.05−1.20), and 1.40 (1.32−1.50), respectively, after adjusting for confounding variables. Considering the associated cardiovascular risk, calcium supplementation for osteoporosis treatment should be administered cautiously.

Oculomics for sarcopenia prediction: a machine learning approach toward predictive, preventive, and personalized medicine.

Aims: Sarcopenia is characterized by a gradual loss of skeletal muscle mass and strength with increased adverse outcomes. Recently, large-scale epidemiological studies have demonstrated a relationship between several chronic disorders and ocular pathological conditions using an oculomics approach. We hypothesized that sarcopenia can be predicted through eye examinations, without invasive tests or radiologic evaluations in the context of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: We analyzed data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training set (80%, randomly selected from 2008 to 2010) data were used to construct the machine learning models. Internal (20%, randomly selected from 2008 to 2010) and external (from the KNHANES 2011) validation sets were used to assess the ability to predict sarcopenia. We included 8092 participants in the final dataset. Machine learning models (XGBoost) were trained on ophthalmological examinations and demographic factors to detect sarcopenia. Results: In the exploratory analysis, decreased levator function (odds ratio [OR], 1.41; P value <0.001), cataracts (OR, 1.31; P value = 0.013), and age-related macular degeneration (OR, 1.38; P value = 0.026) were associated with an increased risk of sarcopenia in men. In women, an increased risk of sarcopenia was associated with blepharoptosis (OR, 1.23; P value = 0.038) and cataracts (OR, 1.29; P value = 0.010). The XGBoost technique showed areas under the receiver operating characteristic curves (AUCs) of 0.746 and 0.762 in men and women, respectively. The external validation achieved AUCs of 0.751 and 0.785 for men and women, respectively. For practical and fast hands-on experience with the predictive model for practitioners who may be willing to test the whole idea of sarcopenia prediction based on oculomics data, we developed a simple web-based calculator application (https://knhanesoculomics.github.io/sarcopenia) to predict the risk of sarcopenia and facilitate screening, based on the model established in this study. Conclusion: Sarcopenia is treatable before the vicious cycle of sarcopenia-related deterioration begins. Therefore, early identification of individuals at a high risk of sarcopenia is essential in the context of PPPM. Our oculomics-based approach provides an effective strategy for sarcopenia prediction. The proposed method shows promise in significantly increasing the number of patients diagnosed with sarcopenia, potentially facilitating earlier intervention. Through patient oculometric monitoring, various pathological factors related to sarcopenia can be simultaneously analyzed, and doctors can provide personalized medical services according to each cause. Further studies are needed to confirm whether such a prediction algorithm can be used in real-world clinical settings to improve the diagnosis of sarcopenia. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00292-3.