Associations of overweight and obesity with cardiometabolic risk factor clusters among Korean adolescents.

This study investigated the association between overweight, obesity, and cardiometabolic risk factor clusters in Korean adolescents. We included 2182 participants (1161 boys and 1021 girls) aged 12-18 years from the Korea National Health and Nutrition Examination Survey (2016-2021). Cardiometabolic risk factors include hypertension, high low-density lipoprotein cholesterol (LDL-C) level, low high-density lipoprotein cholesterol (HDL-C) level, hypertriglyceridemia, high fasting plasma glucose level, elevated alanine aminotransferase level, and hyperuricemia. The average age was 15.1 ± 0.1 years in both boys and girls. The proportion of subjects with ≥ 1, ≥ 2, and ≥ 3 cardiometabolic risk factors was 76.5%, 49.8%, and 22.7% in obese adolescents, and 60.5%, 24.0%, and 9.1%, in overweight adolescents, respectively. Compared to adolescents with underweight/normal weight, the odds ratios (ORs) and 95% confidence intervals for the clustering of cardiometabolic risk factors were at 2.76 (1.74-4.38) for ≥ 1; 3.75 (2.11-6.66) for ≥ 2; and 4.75 (1.70-13.25) for ≥ 3 factors in obese adolescents and 1.88 (1.26-2.81) for ≥ 1 factor in overweight adolescents. Overweight and obese adolescents exhibited high cardiometabolic risk clustering. Prevention and management of overweight/obesity in Korean adolescents are emerging to mitigate health risk associated with this condition.

Association between dental diseases and oral hygiene care and the risk of vertebral fracture: a nationwide cohort study.

Periodontal disease and increased missing teeth were associated with incident vertebral fractures. In contrast, professional dental cleaning and frequent tooth brushing, was associated with a lower risk of vertebral fracture. Better oral hygiene care attenuated the risk associated with dental diseases. PURPOSE: To investigate the association between oral health and the risk of vertebral fractures. METHODS: We included 2,532,253 individuals aged ≥40 years who underwent the Korean National Health Insurance Service health examinations in 2008 and followed up until December 31, 2017. We performed multivariable Cox proportional hazard regression analyses to evaluate the association between dental diseases and oral hygiene care and the risk of vertebral fractures. RESULTS: Over the 9.3-year median follow-up, 1.46% (n = 36,857) experienced vertebral fractures. Individuals with dental diseases had a higher risk of vertebral fracture than those without (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 1.02-1.07 for periodontal diseases; 1.02, 1.00-1.05 for dental caries; 1.12, 1.05-1.20 for ≥15 missing teeth). Good oral hygiene care was associated with a lower vertebral fracture risk (HR 0.89, 95% CI: 0.86-0.91 for ≥1 time/year [vs. <1 time/year] of professional dental cleaning; 0.90, 0.87-0.93 for ≥2 times/day [vs. 0-1 time/day] of toothbrushing). The combined dental diseases was significantly associated with an increased vertebral fracture risk, whereas combined oral hygiene care was associated with further risk reduction. Better oral hygiene care reduced vertebral fracture risk associated with dental diseases (all P <0.001). CONCLUSION: Periodontal disease, dental caries, and an increased number of missing teeth were independently associated with higher risks for vertebral fractures. Conversely, improved oral hygiene care, such as personal dental cleaning and frequent tooth brushing, may modify vertebral fracture risks associated with dental disease.

Association between Dental Diseases and Oral Hygiene Care and the Risk of Dementia: A Retrospective Cohort Study.

OBJECTIVES: To investigate the associations of dental diseases and oral hygiene care with the risk of dementia. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: We conducted a population-based study of individuals in the Korean National Health Insurance System. A total of 2,555,618 participants who underwent cardiovascular and dental screenings in 2008 were included. METHODS: Dental diseases including periodontal diseases, dental caries, and tooth loss were assessed by dentists. Information on oral hygiene care, including professional dental cleaning and the frequency of tooth brushing, was collected using a self-administered questionnaire. Study outcomes were all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: Periodontal diseases [adjusted hazard ratio (aHR) 1.07, 95% CI 1.04-1.09], dental caries (aHR 1.03, 95% CI 1.00-1.05), and 8-14 missing teeth (aHR 1.07, 95% CI 1.02-1.12) were associated with an increased risk of all-cause dementia. In contrast, either professional dental cleaning or frequent tooth brushing were associated with decreased risks of all-cause dementia (aHR 0.91, 95% CI 0.89-0.93 each; aHR 0.83, 95% CI 0.80-0.86 for both). The increased risks by dental diseases were reduced by oral hygiene care: periodontal diseases with professional dental cleaning (aHR 0.94, 95% CI 0.91-0.98) or tooth brushing ≥2 times/day (aHR 0.97, 95% CI 0.94-1.00) and 1 to 7 missing teeth with professional dental cleaning (aHR 0.94, 95% CI 0.89-0.98) or tooth brushing ≥2 times/day (aHR 0.92, 95% CI 0.89-0.95). Consistent results were noted for AD and VaD and in various subgroup analyses. CONCLUSION AND IMPLICATIONS: Periodontal disease, dental caries, and a high number of missing teeth were independently associated with a higher risk of dementia. Conversely, improved oral hygiene care, such as professional dental cleaning and frequent tooth brushing, may modify the risk of dementia associated with dental diseases.

Association of Dental Diseases and Oral Hygiene Care With the Risk of Heart Failure in Patients With Type 2 Diabetes: A Nationwide Cohort Study.

Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow-up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (P<0.001). HRs of HF increased among individuals with ≥15 missing teeth (HR, 1.37 [95% CI, 1.14-1.64]) compared with those without missing teeth. Decreased risk of HF was observed in individuals with ≥1 time/year of professional dental cleaning (HR, 0.93 [95% CI, 0.87-0.99]) and in those with ≥2 times/d of toothbrushing (HR, 0.90 [95% CI, 0.82-0.98]) compared with those without these practices. While combined presence of missing teeth and periodontal disease (P=0.004) or dental caries (P=0.007) increased HF risk, combined oral hygiene care was associated with further HF risk reduction (P=0.024). Better oral hygiene care was associated with decreased HF risk, even as the number of missing teeth increased (P<0.001). Conclusions Among patients with type 2 diabetes, dental diseases and oral hygiene care are important determinants of HF development. Dental disease management and good oral care may prevent HF in patients with type 2 diabetes.

Weight Gain, Comorbidities, and Its Associated Factors Among Korean Adults.

BACKGROUND: Weight gain in adults is associated with an increased risk of obesity-related diseases and high healthcare costs. However, there have been limited studies on weight gain in Asians. This study investigated the prevalence, comorbidities, and associated factors of weight gain in the Korean population. METHODS: This is a cross-sectional study of Korean adults aged 19-64 years who participated in the Korea National Health and Nutritional Examination Survey 2016-2019. We used data from 15,514 adults (subjects 1) to analyze the prevalence of weight gain. Finally, after excluding adults with suspicious debilitating conditions among them, 11,477 adults (subjects 2) were used to analyze comorbidities and associated factors. Weight changes and lifestyle factors were assessed using a self-report questionnaire. We analyzed odds ratios and 95% confidence intervals using multivariable logistic regression analysis to examine factors associated with weight gain. RESULTS: The overall prevalence of weight gain was 25.7% in men and 31.3% in women and decreased significantly with age in both sexes. Weight gain of ≥ 6 kg was evident in 10.5% of men and 9.8% of women and was more pronounced with a higher baseline body mass index (BMI). Most metabolic comorbidities worsened the greater the weight gain. Young age was the strongest associated factor for weight gain. Other factors associated with weight gain were being unmarried, blue-collar job, lower income, and alcohol consumption in men; being married in women; smoking and skipping breakfast in both sexes. CONCLUSION: Weight gain was much more pronounced in younger adults and at a higher baseline BMI in both sexes. Public education and health policies to prevent unnecessary weight gain should be strengthened by considering the associated harmful factors in Korean adults.

Dysregulation of Lipid Droplet Protein Expression in Adipose Tissues and Association with Metabolic Risk Factors in Adult Females with Obesity and Type 2 Diabetes.

BACKGROUND: Adipocyte dysregulation of lipid droplet (LD) metabolism caused by altered expression of LD proteins contributes to obesity-related metabolic diseases. OBJECTIVES: We aimed to investigate whether expression levels of PLIN1, CIDEA, and CIDEC were altered in adipose tissues of women with obesity and type 2 diabetes and whether their alterations were associated with metabolic risk factors. METHODS: Normal-weight (NW; 18.5 kg/m2 < BMI ≤ 25 kg/m2; n = 43), nondiabetic obese (OB; BMI > 30 kg/m2; n = 38), and diabetic obese (OB/DM; BMI > 30 kg/m2, fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%; n = 22) women were recruited. Metabolic parameters were measured, and expressions of PLIN1, CIDEA, CIDEC, and obesity-related genes were quantified in abdominal subcutaneous (SAT) and visceral adipose tissues (VAT). Effects of proinflammatory cytokines, endoplasmic reticulum (ER) stress inducers, and metabolic improvement agents on LD protein gene expressions were investigated in human adipocytes. RESULTS: PLIN1, CIDEA, and CIDEC expressions were lower in SAT and higher in VAT in OB subjects relative to NW subjects; however, they were suppressed in both fat depots in OB/DM subjects relative to OB (P < 0.05). Across the entire cohort, whereas VAT PLIN1 (r = 0.349) and CIDEC expressions (r = 0.282) were positively associated with BMI (P < 0.05), SAT PLIN1 (r = -0.390) and CIDEA expressions (r = -0.565) were inversely associated. After adjustment for BMI, some or all of the adipose LD protein gene expressions were negatively associated with fasting glucose (r = -0.259 or higher) and triglyceride levels (r = -0.284 or higher) and positively associated with UCP1 expression (r = 0.353 or higher) (P < 0.05). In adipocytes, LD protein gene expressions were 55-70% downregulated by increased proinflammatory cytokines and ER stress but 2-4-fold upregulated by the metabolic improvement agents exendin-4 and dapagliflozin (P < 0.05). CONCLUSIONS: The findings suggest that reduction of adipose LD protein expression is involved in the pathogenesis of metabolic disorders in women with obesity and type 2 diabetes and that increasing LD protein expression in adipocytes could control development of metabolic disorders.

Adipose tissue LECT2 expression is associated with obesity and insulin resistance in Korean women.

OBJECTIVE: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-upregulated hepatokine inducing skeletal muscle insulin resistance. The study's aim was to explore whether LECT2 is expressed in human adipose tissue and whether the expression is dysregulated during obesity and associated with obesity-related metabolic disorders. METHODS: This study measured metabolic parameters, serum LECT2, and expression of LECT2 and CD209, a gene encoding a putative receptor for LECT2, in abdominal subcutaneous and visceral adipose tissues in women with obesity (with or without type 2 diabetes) and women with normal weight. The expression/secretion of LECT2 and its putative effects were assessed in human adipocytes. RESULTS: Adipose tissue LECT2 mRNA and serum LECT2 were higher in women with obesity and were significantly correlated with parameters related to insulin resistance. LECT2 was mainly expressed by adipocytes. Both LECT2 and CD209 expression was higher in adipocytes from women with obesity. Incubating adipocytes with substances mimicking the microenvironment of obesity adipose tissue increased LECT2 expression/secretion. LECT2 treatment of adipocytes suppressed insulin-stimulated Akt phosphorylation; it reduced adiponectin (ADIPOQ) and increased leptin (LEP) expression in a CD209-dependent manner. CONCLUSIONS: This study demonstrates that LECT2 expression in adipose tissue is high in patients with obesity and associated with insulin resistance and suggests that adipocyte-derived LECT2 may contribute to adipose tissue dysfunction.

Trends in the high blood glucose and non-alcoholic fatty liver disease among Korean adolescents.

High blood glucose level and non-alcoholic fatty liver disease (NAFLD) in adolescents are long-term risk factors for cardiovascular diseases and poor prognosis. We investigated recent trends of high blood glucose levels and NAFLD among Korean adolescents aged 12-18 years. We conducted a cross-sectional analysis using data of 5,685 adolescents aged 12-18 years from the Korea National Health and Nutrition Examination Surveys (KNHANES), from 2007-2009 to 2016-2018. Linear trends in the prevalence of high blood glucose level, NAFLD, and associated factors were assessed using multivariable logistic regression analyses. During the study period, the odds ratios for high blood glucose level and NAFLD increased significantly in both sexes and in girls, respectively (p for trend <0.05). Over-consumption of total calories in boys and fat intake in boys and girls increased significantly (p for trend <0.05). In Korean adolescents, the prevalence of high blood glucose level and NAFLD has increased recently. Efforts to modify the associated factors and further research to determine the public health measures are warranted to prevent these metabolic abnormalities in adolescents.

Gender Differences in Comorbidities and Attitudes Regarding Weight Control among Young Adults with Obesity in Korea.

INTRODUCTION: Obesity in young adulthood increases the risk for premature death, and the prevalence of obesity rapidly increasing among young adults, particularly in young men. We evaluated the gender differences in accompanying comorbidities and attitudes regarding weight control among young Korean adults with obesity. MATERIALS AND METHODS: We analyzed 2,050 young adults with obesity (1,325 men and 725 women) in the 7th KNHANES (2016-2018) aged 19-44 years, with body mass indexes (BMIs) ≥25.0 kg/m2. The odds ratios (ORs) and 95% confidence intervals (CIs) for poor lifestyle factors and accompanying illnesses as well as self-perceived weight status, weight control efforts, and weight control strategies in men compared to those in women were calculated by multivariate logistic regression analysis. RESULTS: The mean BMIs and waist circumferences were 28.2 ± 0.1 kg/m2 and 93.6 ± 0.2 cm and 28.6 ± 0.1 kg/m2 and 88.7 ± 0.4 cm, in men and women, respectively. The ORs and 95% CIs for abdominal obesity (1.52, 1.11-2.07), hypertension (3.11, 2.20-4.40), hypercholesterolemia (1.45, 1.09-1.93), hypertriglyceridemia (3.37, 2.38-4.78), and elevated alanine transaminase concentration (6.53, 4.56-9.36) were higher in young men compared to those in young women. Despite the higher prevalences of comorbid conditions, the odds of inappropriate weight perception (8.13, 4.17-15.86), lack of weight control efforts (2.20, 1.71-2.84), lack of diet therapy (1.56, 1.13-2.16), lack of pharmacotherapy (13.27, 6.82-25.79), heavy drinking (1.32, 1.02-1.72), current smoking (6.92, 5.00-9.59), and frequent eating out (4.38, 3.35-5.71) were higher among men. However, the odds of not engaging in exercise (0.48, 0.35-0.64) were lower among men compared to that in women. DISCUSSION: Despite their higher prevalences of comorbidities, appropriate weight perception and weight control efforts are insufficient in young men with obesity. These gender differences should be considered to provide tailored programs for weight reduction in young adults with obesity.

Changes in Physical Activity and the Risk of Dementia in Patients With New-Onset Type 2 Diabetes: A Nationwide Cohort Study.

OBJECTIVE: We investigated the association between interval changes in physical activity (PA) and dementia risk among patients with new-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified 133,751 participants newly diagnosed with type 2 diabetes in a health screening (2009-2012), with a follow-up health screening within 2 years (2010-2015). PA level changes were categorized into continuous lack of PA, decreaser, increaser, and continuous PA groups. Dementia was determined using dementia diagnosis codes and antidementia drug prescriptions. RESULTS: During the median follow-up of 4.8 years, 3,240 new cases of all-cause dementia developed. Regular PA was associated with lower risks of all-cause dementia (adjusted hazard ratio [aHR] 0.82; 95% CI 0.75-0.90), Alzheimer disease (AD) (aHR 0.85; 95% CI 0.77-0.95), and vascular dementia (VaD) (aHR 0.78; 95% CI 0.61-0.99). Increasers who started to engage in regular PA had a lower risk of all-cause dementia (aHR 0.86; 95% CI 0.77-0.96). Moreover, the risk was further reduced among those with continuous regular PA: all-cause dementia (aHR 0.73; 95% CI 0.62-0.85), AD (aHR 0.74; 95% CI 0.62-0.88), and VaD (aHR 0.62; 95% CI 0.40-0.94). Consistent results were noted in various subgroup analyses. CONCLUSIONS: Regular PA was independently associated with lower risks of all-cause dementia, AD, and VaD among individuals with new-onset type 2 diabetes. Those with continuous regular PA and, to a lesser extent, those who started to engage in regular PA had a lower risk of dementia. Regular PA should be encouraged to prevent dementia in high-risk populations and those with new-onset type 2 diabetes.

Weight change and the incidence of heart failure in the Korean population: data from the National Health Insurance Health checkup 2005-2015.

AIMS: Heart failure (HF) is associated with obesity, but the relationship between weight change and HF is inconsistent. We examined the relationship between weight change and the incidence of HF in the Korean population. DESIGN: Retrospective cohort study design. METHODS AND RESULTS: A total of 11 210 394 subjects (6 198 542 men and 5 011 852 women) >20 years of age were enrolled in this study. Weight change over 4 years divided into seven categories from weight loss ≥15% to weight gain ≥15%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of HF were analysed. The HR of HF showed a slightly reverse J-shaped curve by increasing weight change in total and >15% weight loss shows the highest HR (HR 1.647) followed by -15 to -10% weight loss (HR = 1.444). When using normal body mass index with stable weight group as a reference, HR of HF decreased as weight increased in underweight subjects and weight gain ≥15% in obesity Stage II showed the highest HR (HR = 2.97). Sustained weight for 4 years in the underweight and obesity Stages I and II increased the incidence of HF (HR = 1.402, 1.092, and 1.566, respectively). CONCLUSION: Both weight loss and weight gain increased HR for HF. Sustained weight in the obesity or underweight categories increased the incidence of HF.

TRIB3 Is Highly Expressed in the Adipose Tissue of Obese Patients and Is Associated With Insulin Resistance.

CONTEXT: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVE: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSION: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.

Endoplasmic reticulum stress increases LECT2 expression via ATF4.

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, insulin resistance, and endoplasmic reticulum (ER) stress. Elevated circulating levels of the hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) have also been noted in NAFLD; however, the mechanism underlying this association is unclear. To investigate a possible link between ER stress/unfolded protein response (UPR) signaling and LECT2 secretion, HepG2 cells were incubated with ER stress inducers with or without an ER stress-reducing chemical chaperone. Additionally, UPR pathway genes were knocked down and overexpressed, and a ChIP assay was performed. In diet-induced obese mice, hepatic expression of LECT2 and activating transcription factor 4 (ATF4) was measured. In HepG2 cells, LECT2 expression was increased by ER stressors, an effect blocked by the chemical chaperone. Among UPR pathway proteins, only knockdown of ATF4 suppressed ER stress-induced LECT2 expression, while overexpression of ATF4 enhanced LECT2 expression. The ChIP assay revealed that ATF4 binds to three putative binding sites on the LECT2 promoter and binding is promoted by an ER stress inducer. In steatotic livers of obese mice, LECT2 and ATF4 expression was concomitantly elevated. Our data indicate that activation of ER stress/UPR signaling induces LECT2 expression in steatotic liver; specifically, ATF4 appears to mediate upregulation of LECT2 transcription.

Relationship of domain-specific quality of life with body mass index and waist circumference in a Korean elderly population.

BACKGROUND: Obesity affects health-related quality of life (QoL); however, their relationship among elderly Asians is not well known. AIMS: Relationship of domain-specific QoL with body mass index (BMI) and waist circumference and the sex differences were investigated using a nationally representative sample of elderly Korean population. METHODS: In the Korea National Health and Nutrition Examination Survey phase VII (2016-2018), 3659 adults aged ≥ 65 years (1551 men and 2108 women) participated. BMI and waist circumference were classified according to Asian- and Korean-specific criteria. QoL was evaluated using the European Quality of Life Scale-Five Dimensions (EQ-5D). Multivariable logistic regressions were used to examine the relationship of QoL with BMI and waist circumference. RESULTS: Men with BMI < 18.5 kg/m2 and ≥ 25.0 kg/m2 had a significant association with poor QoL in mobility and self-care, but no relationship was found with the other domains. Women with BMI ≥ 25.0 kg/m2 had poor QoL in mobility and self-care, and those with BMI ≥ 30.0 kg/m2 had poor QoL in usual activities and pain/discomfort. There was no significant association with anxiety/depression. Both elderly men and women with abdominal obesity had a significant association with poor QoL in mobility, self-care, usual activities, and pain/discomfort; however, there was no significant relationship with waist circumference and anxiety/depression. CONCLUSIONS: The association between QoL and BMI was different according to sex and the domains of QoL. Domain-specific QoL should be considered in the management of body weight of the elderly.

Correlation between Serum Lipid Parameters and Interleukin-10 Concentration in Obese Individuals.

Background: The role of interleukin-10 (IL-10) in humans is controversial because IL-10 has been proposed to exhibit both pro- and anti-inflammatory effects. We aimed to determine the relationships between the changes in these parameters in obese individuals participating in a weight-reduction program. Methods: We measured cardiometabolic parameters including lipid profile and serum IL-10 concentration before and after completion of a 12-week weight-reduction program in 63 non-diabetic obese subjects with a body mass index ≥27 kg/m2 who had comorbid hypertension or dyslipidemia. All the participants were provided with individual intervention sessions designed to implement lifestyle modifications and administered 120 mg orlistat three times daily for 12 weeks. The relationships between changes in serum IL-10 concentration and changes in cardiometabolic risk factors were analyzed. Results: Changes in serum IL-10 concentration were significantly negatively correlated with changes in total cholesterol (r=-0.377), high-density lipoprotein cholesterol (HDL-C; r=-0.377), and low-density lipoprotein cholesterol (LDL-C; r=-0.278) concentrations. However, there were no correlations between changes in serum IL-10 concentration and changes in other cardiometabolic parameters. Conclusion: Serum IL-10 concentration can increase as serum total cholesterol decreases. Additional studies are needed to explore the mechanisms linking changes in serum IL-10 with serum LDL-C and HDL-C concentrations.

TFEB-GDF15 axis protects against obesity and insulin resistance as a lysosomal stress response.

TFEB, a key regulator of lysosomal biogenesis and autophagy, is induced not only by nutritional deficiency but also by organelle stress. Here, we find that Tfeb and its downstream genes are upregulated together with lipofuscin accumulation in adipose tissue macrophages (ATMs) of obese mice or humans, suggestive of obesity-associated lysosomal dysfunction/stress in ATMs. Macrophage-specific TFEB-overexpressing mice display complete abrogation of diet-induced obesity, adipose tissue inflammation and insulin resistance, which is independent of autophagy, but dependent on TFEB-induced GDF15 expression. Palmitic acid induces Gdf15 expression through lysosomal Ca2+-mediated TFEB nuclear translocation in response to lysosomal stress. In contrast, mice fed a high-fat diet with macrophage-specific Tfeb deletion show aggravated adipose tissue inflammation and insulin resistance, accompanied by reduced GDF15 level. Finally, we observe activation of TFEB-GDF15 in ATMs of obese humans as a consequence of lysosomal stress. These findings highlight the importance of the TFEB-GDF15 axis as a lysosomal stress response in obesity or metabolic syndrome and as a promising therapeutic target for treatment of these conditions.

Body mass index trajectories and the risk for Alzheimer's disease among older adults.

The effect of body mass index (BMI) changes and variability on the risk for Alzheimer's disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002-2003), phase 2 (2004-2005), and phase 3 (2006-2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1-15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02-1.29), 1.44 (1.17-1.79), and 1.51 (1.09-2.09) when 2-year BMI loss was 5.1-10.0%, 10.1-15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17-1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.

Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention.

OBJECTIVE: We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. METHODS: People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. RESULTS: The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m2 at 2 months; -4.23 kg and -1.55 kg/m2 at 4 months, and -5.14 kg and -1.89 kg/m2 at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%). CONCLUSIONS: In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.

Early Clinical Outcomes of the Morbidly Obese Patients Who Underwent Laparoscopic Sleeve Gastrectomy by Gastric Cancer Surgeons: the Analysis of Fifty Consecutive Cases.

Purpose: The number of bariatric surgeries performed at our tertiary hospital has gradually increased since the national health insurance began to cover their expenses in January of 2019. This study examined the early surgical outcomes of laparoscopic sleeve gastrectomy (LSG) performed by experienced gastric cancer surgeons. Materials and Methods: We retrospectively reviewed and analyzed data from 50 patients who underwent LSG between November of 2018 and April of 2020 at the Asan Medical Center by 1 of 5 experienced surgeons each of whom performed approximately 100-300 cases of gastrectomy annually. The age, body mass index (BMI), weight, presence of comorbidities, operation time, hospital stay after surgery, postoperative complications, postoperative excess weight loss (EWL), and resolution of comorbidities were examined. Results: The mean age, BMI, and weight were 37.29±9.77 years, 37.12 kg/m2, and 102.00 kg, respectively. The mean operation time and postoperative length of hospital stay were 109.59±35.88 and 5.06±1.20 days, respectively. Two patients (4.00%) had early postoperative complications and postoperative leakage; bleeding and stenosis were not reported. The EWL after 1 and 6 months of operation was 26.55% and 60.34%, respectively. The resolution of diabetes, hypertension, and dyslipidemia after 6 months of operation was 88.89%, 54.54%, and 50.00%, respectively. Conclusion: LSG is safe and effective when performed by an experienced gastric cancer surgeon; however, a long-term follow-up of patients is required.

Female reproductive factors and the risk of Parkinson's disease: a nationwide cohort study.

There are conflicting finds in the literature regarding the association of female estrogen status and the incidence of Parkinson's disease (PD). We aimed to investigate whether female reproductive factors are associated with PD. Using the Korean National Health Insurance System database, 4,729,546 postmenopausal women without PD were identified. The new incidence of PD was defined as subjects with an ICD-10 code for PD (G20) and with a rare intractable disease registration code for PD (V124). The Cox proportional hazard models were used to evaluate the associations of various reproductive factors with incidence of PD. During the median follow-up of 5.84 years, 20,816 individuals were diagnosed with PD. An increased risk of PD was observed in subjects with a later age at menarche (≥ 17 years) compared with reference subjects (13 years ≤ age at menarche ≤ 14 years) (adjusted hazard ratio, aHR 1.10, 95% confidence interval, CI 1.05-1.16). As age at menopause increased, risk of PD decreased (P for trend 0.019). Consistently, decreased risk of PD was observed (aHR 0.91, 95% CI 0.85-0.96) in subjects with longer duration of fertility (≥ 40 years of age) compared with shorter duration of fertility (< 30 years of age). Hormone replacement therapy and oral contraceptives independently increased the risk of PD by 17% and 7%, respectively. Female reproductive factors are independent risk factors for PD, with higher risk associated with shorter lifetime exposure to endogenous estrogen.