Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study: Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun; Endocrinol Metab. 2023;38(6):770-781. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1726

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Abstract PDF Supplementary Material PubReader ePub: Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Diabetes, Obesity and Metabolism
Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults: Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee; Endocrinol Metab. 2022;37(5):781-790. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1532

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Background
Shift work is associated with obesity and metabolic syndrome. However, this association in the normal-weight population remains unclear. This study aimed to investigate whether shift work is associated with normal-weight obesity (NWO).
Methods
From the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset (2008 to 2011), 3,800 full-time workers aged ≥19 years with a body mass index (BMI) ≤25 kg/m² were analysed. We defined NWO as BMI ≤25 kg/m² and body fat percentage ≥25% in men and ≥37% in women. Working patterns were classified into “daytime,” “other than daytime,” and “shift.” Multivariable logistic regression analysis was performed to evaluate the relationship between shift work and NWO.
Results
Shift work was associated with higher odds of NWO than daytime work (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.04 to 2.09) and night/evening work (aOR, 1.87; 95% CI, 1.11 to 3.14) after adjustment for type of work, working hours, age, sex, BMI, 25-hydroxyvitamin D levels, homeostatic model assessment for insulin resistance, and other sociodemographic factors. In subgroup analyses, the association between shift work and NWO was more robust in those aged ≥60 years and those working ≥56 hours/week.
Conclusion
Shift work was associated with NWO in community-dwelling Korean adults, independent of age, sex, BMI, and other covariates.

Citations

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Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work
Sorina Hohor, Cristina Mandanach, Andreea Maftei, Corina Aurelia Zugravu, Marina Ruxandra Oțelea
Antioxidants.2023; 12(4): 959. CrossRef
Normal-Weight Obesity and Metabolic Syndrome in Korean Adults: A Population-Based Cross-Sectional Study
Jeonghyeon Kim, Seamon Kang, Hyunsik Kang
Healthcare.2023; 11(16): 2303. CrossRef
You Can’t Avoid Shift Work? Then Focus on Body Fat Rather than Weight
Eun Kyung Lee
Endocrinology and Metabolism.2022; 37(5): 756. CrossRef

Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging: Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn; Endocrinol Metab. 2022;37(4):630-640. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1430

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Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

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Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty
KAYLONI OLSON, DENISE K. HOUSTON, JOHNATHAN ROSS, RENA R. WING, FELICIA R. SIMPSON, AMBARISH PANDEY, MICHAEL P. WALKUP, MIA YANG, MARK A. ESPELAND
Medicine & Science in Sports & Exercise.2024; 56(4): 717. CrossRef
Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
Biochimica et Biophysica Acta (BBA) - General Subjects.2023; 1867(2): 130281. CrossRef
Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
Jaime A. Gallo-Villegas, Juan C. Calderón
European Journal of Applied Physiology.2023; 123(5): 945. CrossRef

Diabetes, Obesity and Metabolism
Prognostic Value of Triglyceride and Glucose Index for Incident Type 2 Diabetes beyond Metabolic Health and Obesity: Hwi Seung Kim, Jiwoo Lee, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Hong-Kyu Kim, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung; Endocrinol Metab. 2021;36(5):1042-1054. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1184

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Abstract PDF Supplementary Material PubReader ePub: Background
Metabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index.
Methods
The study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group.
Results
During the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively.
Conclusion
MHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

Diabetes, Obesity and Metabolism
Musclin Is Related to Insulin Resistance and Body Composition, but Not to Body Mass Index or Cardiorespiratory Capacity in Adults: Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis Valbuena, Andrés F. Milán, María C. Trillos-Almanza, Sergio Granados, Miguel Peña, Mauricio Estrada-Castrillón, Juan C. Aristizábal, Raúl Narvez-Sanchez, Jaime Gallo-Villegas, Juan C. Calderón; Endocrinol Metab. 2021;36(5):1055-1068. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1104

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Background
We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.
Methods
A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.
Results
The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VO_peak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m² vs. 27.4± 3.6 kg/m²), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VO_peak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.
Conclusion
In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

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Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation
Wonjun Cho, Heeseung Oh, Sung Woo Choi, A. M. Abd El-Aty, Fatma Yeşilyurt, Ji Hoon Jeong, Tae Woo Jung
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Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2
Kaiyi Zhang, Ning Xie, Huaqiong Ye, Jiakun Miao, Boce Xia, Yu Yang, Huanqi Peng, Shuang Xu, Tianwen Wu, Cong Tao, Jinxue Ruan, Yanfang Wang, Shulin Yang
iScience.2024; 27(1): 108590. CrossRef
Myokines: metabolic regulation in obesity and type 2 diabetes
Zhi-Tian Chen, Zhi-Xuan Weng, Jiandie D Lin, Zhuo-Xian Meng
Life Metabolism.2024;[Epub] CrossRef
Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
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European Journal of Applied Physiology.2023; 123(5): 945. CrossRef
Serum Levels of Myonectin Are Lower in Adults with Metabolic Syndrome and Are Negatively Correlated with Android Fat Mass
Jorge L. Petro, María Carolina Fragozo-Ramos, Andrés F. Milán, Juan C. Aristizabal, Jaime A. Gallo-Villegas, Juan C. Calderón
International Journal of Molecular Sciences.2023; 24(8): 6874. CrossRef
The correlation of serum musclin with diabetic nephropathy
Jie Zhang, Jing Shi, Zengguang Cheng, Wenchao Hu
Cytokine.2023; 167: 156211. CrossRef
Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial
Jaime Gallo-Villegas, Leonardo A. Castro-Valencia, Laura Pérez, Daniel Restrepo, Oscar Guerrero, Sergio Cardona, Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis H. Valbuena, Miguel Peña, Andrés F. Milán, Maria C. Trillos-Almanza, Sergio Granados, Juan C.
European Journal of Applied Physiology.2022; 122(2): 331. CrossRef
Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle
Paola Llanos, Jesus Palomero
Cells.2022; 11(24): 4008. CrossRef

Adrenal Gland
Lipid Profiles in Primary Aldosteronism Compared with Essential Hypertension: Propensity-Score Matching Study: Sun Joon Moon, Han Na Jang, Jung Hee Kim, Min Kyong Moon; Endocrinol Metab. 2021;36(4):885-894. Published online August 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.1012

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Background
There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function.
Methods
Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively.
Results
Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed.
Conclusion
PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

Citations

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Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups
Kaiwen Sun, Minghui Gong, Yang Yu, Minghui Yang, Ying Zhang, Yinong Jiang, Wei Song
Frontiers in Endocrinology.2024;[Epub] CrossRef
Meta‐analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism
Qiu‐Gen Zhu, Feng Zhu
The Journal of Clinical Hypertension.2023; 25(1): 13. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
The differences of serum lipid profiles between primary aldosteronism and essential hypertension: a meta-analysis and systematic review
Worapaka Manosroi, Pitchaporn Phudphong, Pichitchai Atthakomol, Mattabhorn Phimphilai
BMC Endocrine Disorders.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism: Ju Hee Lee, Saet-Byel Jung, Seong Eun Lee, Ji Eun Kim, Jung Tae Kim, Yea Eun Kang, Seul Gi Kang, Hyon-Seung Yi, Young Bok Ko, Ki Hwan Lee, Bon Jeong Ku, Minho Shong, Hyun Jin Kim; Endocrinol Metab. 2021;36(3):661-671. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.1023

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Background
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPR^mt) in adipose tissue is associated with obesity in humans and rodents.
Methods
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure
Muchen Wu, Jing Wu, Kai Liu, Minjie Jiang, Fang Xie, Xuehong Yin, Jushan Wu, Qinghua Meng
Chinese Medical Journal.2024; 137(2): 190. CrossRef
Mitochondrial quality control proteases and their modulation for cancer therapy
Jiangnan Zhang, Wenliang Qiao, Youfu Luo
Medicinal Research Reviews.2023; 43(2): 399. CrossRef
Effects of Obesity and Calorie Restriction on Cancer Development
Ekaterina Sergeeva, Tatiana Ruksha, Yulia Fefelova
International Journal of Molecular Sciences.2023; 24(11): 9601. CrossRef
Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity
Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Natalia Gazatova, Larisa Litvinova
International Journal of Molecular Sciences.2023; 24(15): 12012. CrossRef
Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome
Yuan Xie, Shuwen Chen, Zaixin Guo, Ying Tian, Xinyu Hong, Penghui Feng, Qiu Xie, Qi Yu
MedComm.2023;[Epub] CrossRef
The mitochondrial unfolded protein response: A multitasking giant in the fight against human diseases
Zixin Zhou, Yumei Fan, Ruikai Zong, Ke Tan
Ageing Research Reviews.2022; 81: 101702. CrossRef

Diabetes, Obesity and Metabolism
Efficacy and Safety of the New Appetite Suppressant, Liraglutide: A Meta-Analysis of Randomized Controlled Trials: Shinje Moon, Jibeom Lee, Hye Soo Chung, Yoon Jung Kim, Jae Myung Yu, Sung Hoon Yu, Chang-Myung Oh; Endocrinol Metab. 2021;36(3):647-660. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2020.934

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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.

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Pharmacotherapy for obesity: moving towards efficacy improvement
Walmir Coutinho, Bruno Halpern
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
Physiopathology and Treatment of Obesity and Overweight: A Proposal for a New Anorectic
Bruno Silvestrini, Mauro Silvestrini, Mayank Choubey
Journal of Obesity.2024; 2024: 1. CrossRef
Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis
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European Journal of Gastroenterology & Hepatology.2023; 35(1): 1. CrossRef
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Clinical Study
High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly: Youngmi Kim Pak, Hoon Sung Choi, Wook Ha Park, Suyeol Im, P. Monica Lind, Lars Lind, Hong Kyu Lee; Endocrinol Metab. 2021;36(2):436-446. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2020.883

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Background
High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time.
Methods
Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up.
Results
AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose.
Conclusion
These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

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An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data
Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
International Journal of Environmental Research and Public Health.2022; 19(10): 5800. CrossRef
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Clinical Study Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study: Yunjung Cho, Kyungdo Han, Da Hye Kim, Yong-Moon Park, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2021;36(2):424-435. Published online April 14, 2021; DOI: https://doi.org/10.3803/EnM.2020.935

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Background
Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia.
Methods
Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model.
Results
Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer’s disease.
Conclusion
More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.

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Association between metabolic syndrome and risk of incident dementia in UK Biobank
Danial Qureshi, Jennifer Collister, Naomi E. Allen, Elżbieta Kuźma, Thomas Littlejohns
Alzheimer's & Dementia.2024; 20(1): 447. CrossRef
Cumulative exposure to metabolic syndrome affects the risk of psoriasis differently according to age group: a nationwide cohort study in South Korea
Se Young Jung, Kyungdo Han, Jin Hyung Jung, Hyunsun Park, Dong Wook Shin
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Electroacupuncture stimulation improves cognitive ability and regulates metabolic disorders in Alzheimer’s disease model mice: new insights from brown adipose tissue thermogenesis
Ting Li, Junjian Tian, Meng Wu, Yuanshuo Tian, Zhigang Li
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Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study
Tara SR Chen, Ning-Ning Mi, Hubert Yuenhei Lao, Chen-Yu Wang, Wai Leung Ambrose Lo, Yu-Rong Mao, Yan Tang, Zhong Pei, Jin-Qiu Yuan, Dong-Feng Huang
BMC Medicine.2024;[Epub] CrossRef
Clustering of Cardiometabolic Risk Factors and Dementia Incidence in Older Adults: A Cross-Country Comparison in England, the United States, and China
Panagiota Kontari, Chris Fife-Schaw, Kimberley Smith, Lewis A Lipsitz
The Journals of Gerontology: Series A.2023; 78(6): 1035. CrossRef
Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea
Seung-Hwan Lee, Jin Yu, Kyungdo Han, Seung Woo Lee, Sang Youn You, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim
Endocrinology and Metabolism.2023; 38(1): 129. CrossRef
Metabolic syndrome and the risk of postoperative delirium and postoperative cognitive dysfunction: a multi-centre cohort study
Insa Feinkohl, Jürgen Janke, Arjen J.C. Slooter, Georg Winterer, Claudia Spies, Tobias Pischon
British Journal of Anaesthesia.2023; 131(2): 338. CrossRef
Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study
Marcos D. Machado-Fragua, Séverine Sabia, Aurore Fayosse, Céline Ben Hassen, Frank van der Heide, Mika Kivimaki, Archana Singh-Manoux
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Clinical Study
Association between Secondhand Smoke Exposure and Metabolic Syndrome in 118,609 Korean Never Smokers Verified by Self-Reported Questionnaire and Urine Cotinine: Ji Hye Kim, Byung Jin Kim, Young Youl Hyun, Jin Ho Kang; Endocrinol Metab. 2020;35(4):892-900. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.847

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Background
No study has reported the association between secondhand smoke (SHS) exposure and metabolic syndrome (MetS) in self-reported never smokers verified by both self-reported questionnaire and urine cotinine.
Methods
A total of 118,609 self-reported and cotinine-verified never smokers (38,385 male; age 34.8±7.1 years) who participated in the Kangbuk Samsung Health Study between 2011 and 2016 were included. Cotinine-verified never smokers were defined as individuals with urinary cotinine <50 ng/mL. SHS exposure was defined as current exposure to passive smoking indoors at home or workplace.
Results
Prevalence of SHS exposure in the overall population was 22.6% (27.4% for males and 20.3% for females (P<0.001). The overall prevalence of MetS was 6.8% and was higher in males than in females (10.7% vs. 4.9%, P<0.001). In both genders, MetS prevalence was higher in the SHS exposure group than the non-SHS exposure group (11.3% vs. 10.4%, P=0.010 for males; 5.8% vs. 4.6%, P<0.001 for females). However, there was significant gender interaction for the association between SHS exposure and MetS (P for interaction=0.010). In the multivariate regression analyses, SHS exposure was associated with increased MetS odds only in females (odds ratio [95% confidence interval], 1.02 [0.94 to 1.11] in male vs. 1.17 [1.06 to 1.29] in female). In particular, females with SHS exposure of ≥1 hour/day and ≥3 times showed increased odds of MetS compared with those without SHS exposure (1.22 [1.02 to 1.45], 1.30 [1.14 to 1.49]).
Conclusion
This cross-sectional study showed that SHS exposure was significantly associated with prevalence of MetS in self-reported and cotinine-verified female never smokers.

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Combined Influence of Eight Lifestyle Factors on Metabolic Syndrome Incidence: A Prospective Cohort Study from the MECH-HK Study
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Association of environmental tobacco smoke exposure with metabolic syndrome: A longitudinal Cohort Study of 71,055 never smokers
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Diabetes
Comparison of Serum PCSK9 Levels in Subjects with Normoglycemia, Impaired Fasting Glucose, and Impaired Glucose Tolerance: Eugene Han, Nan Hee Cho, Seong-Su Moon, Hochan Cho; Endocrinol Metab. 2020;35(2):480-483. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.480

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We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations in individuals with normoglycemia, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). This was a pilot, cross-sectional study including 92 individuals who had not been diagnosed with or treated for diabetes. We measured PCSK9 levels in three groups of subjects; namely, normoglycemia (n=57), IFG (n=21), and IGT (n=14). Individuals with IFG and IGT showed higher PCSK9 concentrations than those in the normoglycemic group, with the highest serum PCSK9 concentrations found in individuals with IGT (55.25±15.29 ng/mL for normoglycemia, 63.47±17.78 ng/mL for IFG, 72.22±15.46 ng/mL for IGT, analysis of variance P=0.001). There were no significant differences in high- or low-density lipoprotein cholesterol among groups. Serum PCSK9 levels are increased in patients with prediabetes compared to subjects with normoglycemia.

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Emerging Insights on the Diverse Roles of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Chronic Liver Diseases: Cholesterol Metabolism and Beyond
Thomas Grewal, Christa Buechler
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are not associated with severity of liver disease and are inversely related to cholesterol in a cohort of thirty eight patients with liver cirrhosis
Susanne Feder, Reiner Wiest, Thomas S. Weiss, Charalampos Aslanidis, Doris Schacherer, Sabrina Krautbauer, Gerhard Liebisch, Christa Buechler
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Namgok Lecture 2019

Obesity and Metabolism
Impact of Skeletal Muscle Mass on Metabolic Health: Gyuri Kim, Jae Hyeon Kim; Endocrinol Metab. 2020;35(1):1-6. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.1

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Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.

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Original Articles

Clinical Study
Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study: Jung A Kim, Da Hye Kim, Seon Mee Kim, Yong Gyu Park, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi, Kyungdo Han, Hye Jin Yoo; Endocrinol Metab. 2019;34(4):406-414. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.406

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Abstract PDF Supplementary Material PubReader ePub

Background

Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.

Methods

We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.

Results

During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain.

Conclusion

Metabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index.

Citations

Citations to this article as recorded by

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Hye Ah Lee, Hyesook Park
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Dario Iafusco, Roberto Franceschi, Alice Maguolo, Salvatore Guercio Nuzio, Antonino Crinò, Maurizio Delvecchio, Lorenzo Iughetti, Claudio Maffeis, Valeria Calcaterra, Melania Manco
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Daye Diana Choi, Kyung-Ah Park, Kyungdo Han, Sei Yeul Oh
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Tenzin D. Dagpo, Christopher J. Nolan, Viviane Delghingaro-Augusto
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Obesity and metabolism.2020; 17(4): 332. CrossRef

Clinical Study
Association between Serum Gamma-Glutamyltransferase and Prevalence of Metabolic Syndrome Using Data from the Korean Genome and Epidemiology Study: Mi Young Lee, Dae Sung Hyon, Ji Hye Huh, Hae Kyung Kim, Sul Ki Han, Jang Young Kim, Sang Baek Koh; Endocrinol Metab. 2019;34(4):390-397. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.390

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120 Download
14 Web of Science
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Abstract PDF PubReader ePub

Background

The aim of this study was to determine whether there is a positive correlation between gamma-glutamyltransferase (GGT) levels and the prevalence of metabolic syndrome and whether GGT can be used as an easily checkable metabolic index using data from the large-scale Korean Genome and Epidemiology Study (KoGES).

Methods

We obtained data of 211,725 participants of the KoGES. The collected data included age, sex, height, weight, waist circumference, and various biochemical characteristics, including serum GGT levels. The data of study participants who ingested more than 40 g/day of alcohol and who were diagnosed with metabolic syndrome at baseline was excluded. We analyzed the prevalence of metabolic syndrome according to GGT quartiles in both genders.

Results

The GGT level was significantly higher in subjects with metabolic syndrome compared to normal subjects (37.92±48.20 mg/dL vs. 25.62±33.56 mg/dL). The prevalence of metabolic syndrome showed a stepwise increase with GGT quartiles in both male and female subjects. Compared to the lowest GGT quartile, the odds ratio was 1.534 (95% confidence interval [CI], 1.432 to 1.643), 1.939 (95% CI, 1.811 to 2.076), and 2.754 (95% CI, 2.572 to 2.948) in men and 1.155 (95% CI, 1.094 to 1.218), 1.528 (95% CI, 1.451 to 1.609), and 2.022 (95% CI, 1.921 to 2.218) in women with increasing GGT quartile. The cutoff value of GGT predicting risk of metabolic syndrome was 27 IU/L in men and 17 IU/L in women.

Conclusion

We suggested that GGT could be an easily checkable marker for the prediction of metabolic syndrome.

Citations

Citations to this article as recorded by

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Bobbili Tarun Kesava Naidu, Kakarlapudi Santosh Raju, Janapareddi V BhaskaraRao, Nallapati Sunil Kumar
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Elena Raya-Cano, Rafael Molina-Luque, Manuel Vaquero-Abellán, Guillermo Molina-Recio, Rocío Jiménez-Mérida, Manuel Romero-Saldaña
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Luan Manh Chu, Chandima Karunanayake, Palok Aich, Markus Hecker, Punam Pahwa
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