Diabetes & Metabolism Journal

Original Article

Others
Serum Magnesium Levels Are Negatively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Mellitus: A Real-World Study: Man-Rong Xu, Ai-Ping Wang, Yu-Jie Wang, Jun-Xi Lu, Li Shen, Lian-Xi Li; Diabetes Metab J. 2024;48(6):1147-1159. Published online May 29, 2024; DOI: https://doi.org/10.4093/dmj.2023.0401

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Background
There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM.
Methods
This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893).
Results
After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P<0.001 for trend; abdominal obesity: 71.5%, 70.5%, 68.2%, 66.4%, and 64.5%, respectively, P=0.001 for trend). After controlling for confounders, there were clearly negative associations of serum magnesium levels and quintiles with obesity and abdominal obesity in T2DM. Moreover, C-reactive protein partly mediates the effect of serum magnesium on obesity and abdominal obesity (P=0.016 and P=0.004, respectively).
Conclusion
The significantly negative relationship between serum magnesium and the risk of obesity and abdominal obesity was observed in T2DM. Furthermore, the independently negative association of serum magnesium with obesity may be explained by its anti-inflammatory functions. Serum magnesium levels may be applied to assess the risk of obesity and abdominal obesity in T2DM.

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Magnesium Matters: A Comprehensive Review of Its Vital Role in Health and Diseases
Ghizal Fatima, Andrej Dzupina, Hekmat B Alhmadi, Aminat Magomedova, Zainab Siddiqui, Ammar Mehdi, Najah Hadi
Cureus.2024;[Epub] CrossRef

Reviews

Metabolic Risk/Epidemiology
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism: Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan; Diabetes Metab J. 2024;48(3):354-372. Published online April 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0277

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Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

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Diabetes and Osteoarthritis: Exploring the Interactions and Therapeutic Implications of Insulin, Metformin, and GLP-1-Based Interventions
Iryna Halabitska, Liliia Babinets, Valentyn Oksenych, Oleksandr Kamyshnyi
Biomedicines.2024; 12(8): 1630. CrossRef
The Effect of Tirzepatide on Body Composition in People with Overweight and Obesity: A Systematic Review of Randomized, Controlled Studies
Vincenzo Rochira, Carla Greco, Stefano Boni, Francesco Costantino, Leonardo Dalla Valentina, Eleonora Zanni, Leila Itani, Marwan El Ghoch
Diseases.2024; 12(9): 204. CrossRef
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zhikai Zheng, Yao Zong, Yiyang Ma, Yucheng Tian, Yidan Pang, Changqing Zhang, Junjie Gao
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Recent Advances and Therapeutic Benefits of Glucagon-Like Peptide-1 (GLP-1) Agonists in the Management of Type 2 Diabetes and Associated Metabolic Disorders
John O Olukorode, Dolapo A Orimoloye, Nwachukwu O Nwachukwu, Chidera N Onwuzo, Praise O Oloyede, Temiloluwa Fayemi, Oluwatobi S Odunaike, Petra S Ayobami-Ojo, Nwachi Divine, Demilade J Alo, Chukwurah U Alex
Cureus.2024;[Epub] CrossRef
Incretin hormones: Revolutionizing the treatment landscape for kidney and liver diseases in type 2 diabetes and obesity
Jae Hyun Bae, Young Min Cho
Journal of Diabetes Investigation.2024;[Epub] CrossRef
Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism
Jorge F.A. Model, Rafaella S. Normann, Éverton L. Vogt, Maiza Von Dentz, Marjoriane de Amaral, Rui Xu, Tsvetan Bachvaroff, Poli Mara Spritzer, J. Sook Chung, Anapaula S. Vinagre
Biochemical Pharmacology.2024; 230: 116623. CrossRef
Progress in pediatric cardiology VSI: Cardiovascular disease in pediatrics lipoprotein(a) in atherosclerotic cardiovascular disease, type 2 diabetes, and liver disease
Kathryn L. Williams, Maya Augustine, Eru Sujakhu, Justine Magadia, Lindsay Crawford, Aimee Knott, Skyler Hamilton, Uzoma Obiaka
Progress in Pediatric Cardiology.2024; : 101775. CrossRef
Changes in 24-Hour Urine Chemistry in Patients with Nephrolithiasis during Weight Loss with Glucagon-Like Peptide 1–Based Therapies
Karen Feghali, Xilong Li, Naim M. Maalouf
Kidney360.2024; 5(11): 1706. CrossRef

Pathophysiology
Dysfunctional Mitochondria Clearance in Situ: Mitophagy in Obesity and Diabetes-Associated Cardiometabolic Diseases: Songling Tang, Di Hao, Wen Ma, Lian Liu, Jiuyu Gao, Peng Yao, Haifang Yu, Lu Gan, Yu Cao; Diabetes Metab J. 2024;48(4):503-517. Published online February 15, 2024; DOI: https://doi.org/10.4093/dmj.2023.0213

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Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca²⁺ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.

Citations

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Mitophagy in the Pathogenesis of Obesity-Associated Cardiovascular Diseases: New Mechanistic and Therapeutic Insights
Kexin Huang, Jun Ren
Trends in Medical Research.2024; 19(1): 112. CrossRef
A review: Polysaccharides targeting mitochondria to improve obesity
Yongchao Chen, Rong Gao, Jun Fang, Sujuan Ding
International Journal of Biological Macromolecules.2024; 277: 134448. CrossRef
Iron chelators as mitophagy agents: Potential and limitations
Tereza Brogyanyi, Zdeněk Kejík, Kateřina Veselá, Petr Dytrych, David Hoskovec, Michal Masařik, Petr Babula, Robert Kaplánek, Tomáš Přibyl, Jaroslav Zelenka, Tomáš Ruml, Martin Vokurka, Pavel Martásek, Milan Jakubek
Biomedicine & Pharmacotherapy.2024; 179: 117407. CrossRef
Influence of Mitochondrial NAD(P) + Transhydrogenase (NNT) on Hypothalamic Inflammation and Metabolic Dysfunction Induced by a High-Fat Diet in Mice
Giovanna Leite Santos, Ericka Francislaine Dias Costa, Ana Paula Dalla Costa, Ariane Maria Zanesco, Marcela Reymond Simoes, Fábio Rogério, Daniele Masselli Rodrigues Demolin, Claudia Daniele Carvalho Navarro, Lício Augusto Velloso, Annelise Francisco, Rog
Hormone and Metabolic Research.2024;[Epub] CrossRef

Sulwon Lecture 2023

Metabolic Risk/Epidemiology
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective: Inha Jung, Dae-Jeong Koo, Won-Young Lee; Diabetes Metab J. 2024;48(3):327-339. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0350

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It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.

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Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats
Haoru Duan, Shanshan Song, Rui Li, Suqin Hu, Shuting Zhuang, Shaoyang liu, Xiaolu Li, Wei Gao
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
Jaehyun Bae, Eugene Han, Hye Won Lee, Cheol-Young Park, Choon Hee Chung, Dae Ho Lee, Eun-Hee Cho, Eun-Jung Rhee, Ji Hee Yu, Ji Hyun Park, Ji-Cheol Bae, Jung Hwan Park, Kyung Mook Choi, Kyung-Soo Kim, Mi Hae Seo, Minyoung Lee, Nan-Hee Kim, So Hun Kim, Won-
Diabetes & Metabolism Journal.2024; 48(6): 1015. CrossRef

Original Articles

Basic Research
Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition: Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong; Diabetes Metab J. 2023;47(6):784-795. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0261

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Background
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors.
Methods
Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice.
Results
Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus.
Conclusion
This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Citations

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Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
Jae Hyun Bae
Diabetes & Metabolism Journal.2024; 48(1): 157. CrossRef
Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong
Diabetes & Metabolism Journal.2024; 48(1): 159. CrossRef

Metabolic Risk/Epidemiology
Differential Impact of Obesity on the Risk of Diabetes Development in Two Age Groups: Analysis from the National Health Screening Program: Tae Kyung Yoo, Kyung-Do Han, Yang-Hyun Kim, Ga Eun Nam, Sang Hyun Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2023;47(6):846-858. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0242

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Background
The effect of obesity on the development of type 2 diabetes mellitus (DM) in different age groups remains unclear. We assessed the impact of obesity on the development of DM for two age groups (40-year-old, middle age; 66-year-old, older adults) in the Korean population.
Methods
We analyzed Korean National Health Insurance Service data of 4,145,321 Korean adults with 40- and 66-year-old age without DM, between 2009 and 2014. Participants were followed up until 2017 or until the diagnosis of DM. We assessed the risk of DM based on the body mass index and waist circumference of the participants. Multiple confounding factors were adjusted.
Results
The median follow-up duration was 5.6 years. The association of general and abdominal obesity with the risk of DM development was stronger in the 40-year-old group (general obesity: hazard ratio [HR], 3.566, 95% confidence interval [CI], 3.512 to 3.622; abdominal obesity: HR, 3.231; 95% CI, 3.184 to 3.278) than in the 66-year-old group (general obesity: HR, 1.739; 95% CI, 1.719 to 1.759; abdominal obesity: HR, 1.799; 95% CI, 1.778 to 1.820). In the 66-year-old group, abdominal obesity had a stronger association with the development of DM as compared to general obesity. In the 40-year-old group, general obesity had a stronger association with the risk of DM development than abdominal obesity.
Conclusion
The influence of general and abdominal obesity on the development of DM differed according to age. In older adults, abdominal obesity had a stronger association with DM development than general obesity.

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Association of Body Composition Changes with the Development of Diabetes Mellitus: A Nation-Wide Population Study
Hyung Jun Kim, Hyung-Woo Lee, Min-Kyoung Kang, Gwang Hyun Leem, Min-Ho Kim, Tae-Jin Song
Diabetes & Metabolism Journal.2024; 48(6): 1093. CrossRef

Review

Basic Research
Adipose Tissue and Metabolic Health: Sung-Min An, Seung-Hee Cho, John C. Yoon; Diabetes Metab J. 2023;47(5):595-611. Published online July 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0011

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In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.

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Original Articles

Basic Research
CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice: Jongsu Jeon, Dohyun Lee, Bobae Kim, Bo-Yoon Park, Chang Joo Oh, Min-Ji Kim, Jae-Han Jeon, In-Kyu Lee, Onyu Park, Seoyeong Baek, Chae Won Lim, Dongryeol Ryu, Sungsoon Fang, Johan Auwerx, Kyong-Tai Kim, Hoe-Yune Jung; Diabetes Metab J. 2023;47(5):653-667. Published online April 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0244

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Background
CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated.
Methods
KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis.
Results
CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD⁺), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1).
Conclusion
Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD⁺ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

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Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models
Alessia De Masi, Nadège Zanou, Keno Strotjohann, Dohyun Lee, Tanes I. Lima, Xiaoxu Li, Jongsu Jeon, Nicolas Place, Hoe‐Yune Jung, Johan Auwerx
Advanced Science.2024;[Epub] CrossRef

Lifestyle
Ultra-Processed Food Consumption and Obesity in Korean Adults: Jee-Seon Shim, Kyoung Hwa Ha, Dae Jung Kim, Hyeon Chang Kim; Diabetes Metab J. 2023;47(4):547-558. Published online April 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0026

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Background
This study aimed to investigate the association between consumption of ultra-processed foods (UPF) and obesity in Korean adults.
Methods
We included the Cardiovascular and Metabolic Diseases Etiology Research Center cohort study baseline data of adults aged 30 to 64 years who completed a validated food frequency questionnaire. UPF was defined using the NOVA food classification. Multivariable linear and logistic regression analyses were performed to assess the association of dietary energy contribution of UPF with obesity indicators (body mass index [BMI], obesity, waist circumference [WC], and abdominal obesity).
Results
Consumption of UPF accounted for 17.9% of total energy intake and obesity and abdominal obesity prevalence was 35.4% and 30.2%, respectively. Compared with those in the lowest quartile of UPF consumption, adults in the highest quartile had greater BMI (β=0.36; 95% confidence interval [CI], 0.15 to 0.56), WC (β=1.03; 95% CI, 0.46 to 1.60), higher odds of having obesity (odds ratio [OR], 1.24; 95% CI, 1.07 to 1.45), and abdominal obesity (OR, 1.34; 95% CI, 1.14 to 1.57), after adjusting for sociodemographic characteristics, health-related behaviors, and family history of diseases. Dose-response associations between UPF consumption and obesity indicators were consistently found (all P trend <0.01). However, the strength of association was halved for all obesity indicators after further adjustments for total energy intake and overall diet quality score, and the trend toward association for obesity and WC disappeared.
Conclusion
Our finding supports the evidence that consumption of UPF is positively associated with obesity among Korean adults.

Citations

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Ultra-processed food consumption and increased risk of metabolic syndrome in Korean adults: A cross-sectional analysis of the KNHANES 2016–2020
Hansol Park, Youngmi Lee, Jinah Hwang, Yujin Lee
Nutrition.2024; 122: 112374. CrossRef
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Ji A Seo
Diabetes & Metabolism Journal.2024; 48(4): 713. CrossRef
Association of maternal ultra-processed food consumption during pregnancy with atopic dermatitis in infancy: Korean Mothers and Children’s Environmental Health (MOCEH) study
Won Jang, Minji Kim, Eunhee Ha, Hyesook Kim
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Diet quality partially mediates the association between ultraprocessed food consumption and adiposity indicators
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Others
Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity: Guanhua Lu, Huanhuan Gao, Zhiyong Dong, Shuwen Jiang, Ruixiang Hu, Cunchuan Wang; Diabetes Metab J. 2023;47(4):559-570. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0226

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Background
MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed.
Methods
We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared.
Results
Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM.
Conclusion
We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

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Early changes of microRNAs in blood one month after bariatric surgery
Guanhua Lu, Huanhuan Gao, Ruixiang Hu, Ji Miao, Zhiyong Dong, Cunchuan Wang, Xinxin Chen
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef

Metabolic Risk/Epidemiology
The Risk of Type 2 Diabetes Mellitus according to Changes in Obesity Status in Late Middle-Aged Adults: A Nationwide Cohort Study of Korea: Joon Ho Moon, Yeonhoon Jang, Tae Jung Oh, Se Young Jung; Diabetes Metab J. 2023;47(4):514-522. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0159

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Background
Although obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), there is scant data on discriminating the contribution of previous obesity and recent weight gain on developing T2DM.
Methods
We analyzed the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 where Korean residents underwent biennial health checkups. Participants were classified into four groups according to their obesity status (body mass index [BMI] ≥25 kg/m²) before and after turning 50 years old: maintaining normal (MN), becoming obese (BO), becoming normal (BN), and maintaining obese (MO). Cox proportional hazards regression model was used to estimate the risk of T2DM factoring in the covariates age, sex, BMI, presence of impaired fasting glucose or hypertension, family history of diabetes, and smoking status.
Results
A total of 118,438 participants (mean age, 52.5±1.1 years; men, 45.2%) were prospectively evaluated for incident T2DM. A total of 7,339 (6.2%) participants were diagnosed with T2DM during a follow-up period of 4.8±2.6 years. Incidence rates of T2DM per 1,000 person-year were 9.20 in MN, 14.81 in BO, 14.42 in BN, 21.38 in MO. After factoring in covariates, participants in the groups BN (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04 to 1.27) and MO (aHR, 1.14; 95% CI, 1.06 to 1.24) were at increased risk of developing T2DM compared to MN, whereas BO (hazard ratio, 1.06; 95% CI, 0.96 to 1.17) was not.
Conclusion
Having been obese before 50 years old increased the risk of developing T2DM in the future, but becoming obese after 50 did not. Therefore, it is important to maintain normal weight from early adulthood to prevent future metabolic perturbations.

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Accounting for time-varying exposures and covariates in the relationship between obesity and diabetes: analysis using parametric g-formula
Boyoung Park, Junghyun Yoon, Thi Xuan Mai Tran
Journal of Epidemiology and Community Health.2024; 78(11): 729. CrossRef
Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study
Ji-Hee Sung, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
Diabetes & Metabolism Journal.2024; 48(6): 1105. CrossRef

Metabolic Risk/Epidemiology
Novel Asian-Specific Visceral Adiposity Indices Are Associated with Chronic Kidney Disease in Korean Adults: Jonghwa Jin, Hyein Woo, Youngeun Jang, Won-Ki Lee, Jung-Guk Kim, In-Kyu Lee, Keun-Gyu Park, Yeon-Kyung Choi; Diabetes Metab J. 2023;47(3):426-436. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0099

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Background
The Chinese visceral adiposity index (CVAI) and new visceral adiposity index (NVAI) are novel indices of visceral adiposity used to predict metabolic and cardiovascular diseases in Asian populations. However, the relationships of CVAI and NVAI with chronic kidney disease (CKD) have not been investigated. We aimed to characterize the relationships of CVAI and NVAI with the prevalence of CKD in Korean adults.
Methods
A total of 14,068 participants in the 7th Korea National Health and Nutrition Examination Survey (6,182 men and 7,886 women) were included. Receiver operating characteristic (ROC) analyses were employed to compare the associations between indices of adiposity and CKD, and a logistic regression model was used to characterize the relationships of CVAI and NVAI with CKD prevalence.
Results
The areas under the ROC curves for CVAI and NVAI were significantly larger than for the other indices, including the visceral adiposity index and lipid accumulation product, in both men and women (all P<0.001). In addition, high CVAI or NVAI was significantly associated with a high CKD prevalence in both men (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31 to 3.48 in CVAI and OR, 6.47; 95% CI, 2.91 to 14.38 in NVAI, P<0.05) and women (OR, 4.87; 95% CI, 1.85 to 12.79 in CVAI and OR, 3.03; 95% CI, 1.35 to 6.82 in NVAI, P<0.05); this association remained significant after adjustment for multiple confounding factors in men and women.
Conclusion
CVAI and NVAI are positively associated with CKD prevalence in a Korean population. CVAI and NVAI may be useful for the identification of CKD in Asian populations, including in Korea.

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Accessing the relationship between six surrogate insulin resistance indexes and the incidence of rapid kidney function decline and the progression to chronic kidney disease among middle-aged and older adults in China: Results from the China health and ret
Siti Liu, Honglin Sun, Jia Liu, Guang Wang
Diabetes Research and Clinical Practice.2024; 212: 111705. CrossRef
Association between visceral adiposity index and incidence of diabetic kidney disease in adults with diabetes in the United States
Chunyao Li, Gang Wang, Jiale Zhang, Weimin Jiang, Shuwu Wei, Wenna Wang, Shuyv Pang, Chenyv Pan, Weiwei Sun
Scientific Reports.2024;[Epub] CrossRef
Association between lipid accumulation product index and chronic kidney disease: A systematic review and meta-analysis
Feixiang Wu, Chenmin Cui, Junping Wu, Yunqing Wang
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Linear associations of Chinese visceral adiposity index and its change with hyperuricemia: A prospective cohort study
Jia Chen, Xuejiao Liu, Shuai Lu, Siliang Man, Liang Zhang, Xiaojie Xu, Wei Deng, Xieyuan Jiang
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Complications
Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study: Se-Won Lee, Kyungdo Han, Hyuk-Sang Kwon; Diabetes Metab J. 2023;47(2):242-254. Published online January 19, 2023; DOI: https://doi.org/10.4093/dmj.2022.0001

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Background
Body mass index (BMI) is a risk factor for the type 2 diabetes (T2DM), and T2DM accompanies various complications, such as fractures. We investigated the effects of BMI and T2DM on fracture risk and analyzed whether the association varied with fracture locations.
Methods
This study is a nationwide population-based cohort study that included all people with T2DM (n=2,746,078) who received the National Screening Program during 2009–2012. According to the anatomical location of the fracture, the incidence rate and hazard ratio (HR) were analyzed by dividing it into four categories: vertebra, hip, limbs, and total fracture.
Results
The total fracture had higher HR in the underweight group (HR, 1.268; 95% CI, 1.228 to 1.309) and lower HR in the obese group (HR, 0.891; 95% CI, 0.882 to 0.901) and the morbidly obese group (HR, 0.873; 95% CI, 0.857 to 0.89), compared to reference (normal BMI group). Similar trends were observed for HR of vertebra fracture. The risk of hip fracture was most prominent, the risk of hip fracture increased in the underweight group (HR, 1.896; 95% CI, 1.178 to 2.021) and decreased in the obesity (HR, 0.643; 95% CI, 0.624 to 0.663) and morbidly obesity group (HR, 0.627; 95% CI, 0.591 to 0.665). Lastly, fracture risk was least affected by BMI for limbs.
Conclusion
In T2DM patients, underweight tends to increase fracture risk, and overweight tends to lower fracture risk, but association between BMI and fracture risk varied depending on the affected bone lesions.

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Dysuricemia—A New Concept Encompassing Hyperuricemia and Hypouricemia
Naoyuki Otani, Motoshi Ouchi, Einosuke Mizuta, Asuka Morita, Tomoe Fujita, Naohiko Anzai, Ichiro Hisatome
Biomedicines.2023; 11(5): 1255. CrossRef
Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study (Diabetes Metab J 2023;47:242-54)
Se-Won Lee, Kyungdo Han, Hyuk-Sang Kwon
Diabetes & Metabolism Journal.2023; 47(3): 439. CrossRef
Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study (Diabetes Metab J 2023;47:242-54)
So Young Park
Diabetes & Metabolism Journal.2023; 47(3): 437. CrossRef
Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Xin Wang, Fengyi Zhang, Yufeng Zhang, Jiayi Zhang, Yingli Sheng, Wenbo Wang, Yujie Li
Osteoporosis International.2023; 34(12): 2013. CrossRef

Sulwon Lecture 2021

Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c): Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim; Diabetes Metab J. 2022;46(3):402-413. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0092

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Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPR^mt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

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Review

Guideline/Fact Sheet
Effect of Carbohydrate-Restricted Diets and Intermittent Fasting on Obesity, Type 2 Diabetes Mellitus, and Hypertension Management: Consensus Statement of the Korean Society for the Study of Obesity, Korean Diabetes Association, and Korean Society of Hypertension: Jong Han Choi, Yoon Jeong Cho, Hyun-Jin Kim, Seung-Hyun Ko, Suk Chon, Jee-Hyun Kang, Kyoung-Kon Kim, Eun Mi Kim, Hyun Jung Kim, Kee-Ho Song, Ga Eun Nam, Kwang Il Kim, Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO), Committee of Clinical Practice Guidelines and Committee of Food and Nutrition, Korean Diabetes Association (KDA), Policy Committee of Korean Society of Hypertension (KSH), Policy Development Committee of National Academy of Medicine of Korea (NAMOK); Diabetes Metab J. 2022;46(3):355-376. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0038

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Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

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Maria G. Lange, Alice A. Coffey, Paul C. Coleman, Thomas M. Barber, Thijs Van Rens, Oyinlola Oyebode, Sally Abbott, Petra Hanson
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Low-Carbohydrate Dietary Interventions for Metabolic Control in Individuals With Type 2 Diabetes Mellitus: An Overview of Systematic Reviews
Mileni Vanti Beretta, Cíntia Aparecida Oliveira Flores, Gabriella Fontes Colameo, Luana Weissheimer Echabe, Fernanda Michielin Busnello
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Adherence to the nutritional recommendations according to diabetes status in Korean adults: a cross-sectional study
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