Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation: Xin Li, Aikebaier Aili, Yusujiang Tusuntuoheti, Yusunjiang Aierken, Kelimu Abudureyimu, Weihui Liu; Received May 4, 2025 Accepted November 23, 2025 Published online January 15, 2026; DOI: https://doi.org/10.4093/dmj.2025.0392 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Obesity serves as a predominant factor in the progression of metabolic syndrome and type 2 diabetes mellitus. While sleeve gastrectomy (SG) is a well-established surgical intervention, its impact on appetite-regulating hormones, such as ghrelin (GHRL), is limited. Sleeve gastrectomy combined with fundoplication (SGFD) has emerged as a potential strategy to improve metabolic outcomes by modifying both gastric anatomy and gut-brain signaling.
Methods
Sixty-five Sprague-Dawley rats were enrolled. After 8 weeks of high-fat feeding, 48 rats developed diet-induced obesity (DIO). These rats were randomized into four experimental groups: DIO control, sham-operated, SG, and SGFD, alongside a normal control cohort. Biochemical indicators, hormonal fluctuations, and insulin responsiveness were analyzed. Molecular expressions were evaluated through quantitative real-time polymerase chain reaction and Western blotting.
Results
SGFD reduced body weight (−24.7%), food intake (−28.3%), fasting glucose (−37.5%), triglycerides (−42.6%), and serum GHRL (−51.2%) compared with the DIO group (P<0.01). Gastric GHRL, preproghrelin, and ghrelin O-acyltransferase (GOAT) expression were suppressed. Hypothalamic neuropeptide Y (NPY) was downregulated, and AMP-activated protein kinase (AMPK) signaling was robustly enhanced across various tissues. SGFD also improved insulin receptor substrate-1 (IRS-1), glucose transporter type 4 (GLUT4), β-cell function, hepatic lipid oxidation, and brown adipose thermogenesis. SGFD outperformed SG in most metabolic and molecular outcomes (P<0.05).
Conclusion
SGFD provides superior metabolic benefits over SG alone by suppressing GHRL signaling and activating systemic AMPK pathways. SGFD represents a promising surgical strategy for obesity and metabolic syndrome.

Guideline/Statement/Fact Sheet
Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society: Jong Han Choi, SuJin Song, Soo Kyoung Kim, Jae Won Cho, Jae Hyun Bae, Shinje Moon, Jeong Hyun Lim, YeonHee Lee, Ji-Yun Hwang, YoonJu Song, Sang Soo Kim; Diabetes Metab J. 2026;50(1):32-46. Published online January 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.0848

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Background
Excess intake of added sugars contributes to obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and premature mortality. Sugar-sweetened beverages (SSBs), the main source of added sugars, are consistently linked to adverse outcomes. Artificially sweetened beverages (ASBs) have been suggested as short-term substitutes, but evidence regarding benefits and harms remains inconclusive, and guidance is lacking.
Methods
This consensus statement draws on a structured evidence review combining two approaches: an updated meta-analysis of randomized controlled trials (RCTs) assessing short- to intermediate-term effects of replacing SSBs with ASBs on weight and metabolic outcomes; and an umbrella review of systematic reviews of cohort studies evaluating long-term associations of SSBs and ASBs with major outcomes, including mortality, CVD, and T2DM.
Results
In 14 RCTs (3–76 weeks), replacing SSBs with ASBs produced modest reductions in body weight (–0.73 kg) and body fat (–0.72%), with inconsistent effects on glycemic and cardiometabolic markers. Evidence from 20 systematic reviews of cohorts (up to 34 years follow-up) showed that higher intake of both SSBs and ASBs was associated with increased risks of T2DM, CVD, and mortality, with relative risks for ASBs similar to those for SSBs.
Conclusion
ASBs may serve as a short-term substitution for individuals with high SSB intake, particularly those at elevated metabolic risk. However, regular or long-term use is not recommended due to uncertain safety and potential reinforcement of sweet preference. Public health strategies should emphasize reducing both SSBs and ASBs, prioritizing water and unsweetened beverages as the ultimate goal.

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Do Not Replace Your Sugar, Simply Eat Less!
Jeehyun Lee, Sunghwan Suh
Diabetes & Metabolism Journal.2026; 50(1): 30. CrossRef

Metabolic Risk/Epidemiology
Clinical and Preclinical Obesity in Korean Adults from 2014 to 2023: Hun Jee Choe, Jean-Pierre Després, John P. H. Wilding, Donna H. Ryan, Soo Lim; Diabetes Metab J. 2026;50(1):127-138. Published online January 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.0697

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Abstract PDF Supplementary Material PubReader ePub: Background
A new diagnostic framework for clinical obesity, proposed by the Lancet Commission, defines obesity as excess adiposity with organ dysfunction, offering a more functional assessment than traditional body mass index (BMI)-based classification. However, it has not been applied to Asian populations, where obesity-related complications arise at lower BMI thresholds.
Methods
We analyzed 57,863 Korean adults aged ≥20 years from the 2014 to 2023 Korea National Health and Nutrition Examination Survey (KNHANES), a nationally representative, cross-sectional dataset. Clinical obesity was defined as excess adiposity with ≥1 obesity-related complication or functional limitation; preclinical obesity was defined as excess adiposity without complications. Age, sex, and temporal trends were examined and compared with BMI-based classifications using complex sampling weights and age-standardization.
Results
The prevalence of clinical obesity and preclinical obesity was 31.2% and 8.1%, respectively. Among those with BMI-defined obesity (≥25.0 kg/m²), 20.1% had no complications, while 19.4% of overweight individuals (BMI 23.0–24.9 kg/m²) met clinical obesity criteria. Clinical obesity increased with age despite stable BMI, driven by metabolic and functional decline. Cancer prevalence was highest among individuals with clinical obesity (1.77%). Applying Western waist circumference cutoffs drastically reduced the estimated prevalence of clinical obesity to 13.1%. Longitudinal analyses showed a rising trend in clinical obesity over ime.
Conclusion
This is the first large-scale study to apply the clinical obesity framework in an Asian population. The framework identifies high-risk individuals missed by BMI al

Metabolic Risk/Epidemiology
Maternal Galectins and Glucose Regulation in Pregnancy: Chronic vs. Acute Metabolic Adaptations: Mariana G. Garcia, Ebba Hamann, Evelyn A. Huhn, Karen Forbes, Pia Roser, Marie-Therese Weiser-Fuchs, Anna M. Dieberger, Bence Csapo, Barbara Obermayer-Pietsch, Mireille N.M. van Poppel, Herbert Fluhr, Evelyn Jantscher-Krenn, Sandra M. Blois; Received May 8, 2025 Accepted August 21, 2025 Published online December 29, 2025; DOI: https://doi.org/10.4093/dmj.2025.0401 [Epub ahead of print]

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Galectins (gal) are glycan-binding proteins that regulate maternal adaptations during pregnancy, but their role in pregnancy-associated metabolic homeostasis is unclear. This study characterizes the maternal galectin profile in response to an oral glucose tolerance test (OGTT) in pregnant women with varying body weight.
Methods
In a two-center prospective study, pregnant women were recruited into two cohorts: low-risk (LR) with normal weight and high-risk (HR) with overweight or obesity. Circulating levels of gal-1, -3, -7, and -9 were measured at fasting, 1 hour, and 2 hours during the OGTT between 24 and 28 weeks of gestation. Correlations with clinical and metabolic parameters were assessed (HMO study: ClinicalTrials.gov Identifier NCT05496712; FitFor2 trial: trial registration number NTR1139).
Results
Fasting gal-3 and gal-9 were elevated in the HR cohort compared to the LR cohort. Body mass index was positively associated with gal-3 and gal-9, while gal-3 was also linked to insulin sensitivity. After glucose challenge, gal-1, -3, -7, and -9 decreased in the LR cohort; in the HR cohort, only gal-1 and gal-7 decreased after 2 hours, while gal-3 and gal-9 remained unchanged. Gal-1 correlated positively with homeostasis model assessment for insulin resistance (HOMA-IR) and inversely with insulin sensitivity across the OGTT in the LR cohort, but some of these correlations were not observed in the HR cohort.
Conclusion
Galectins exhibited distinct patterns of association with glucose homeostasis during the second trimester of pregnancy. Gal-3 and gal-9 are associated with chronic conditions such as pre-pregnancy obesity and insulin resistance, whereas gal-1 appears to be particularly sensitive to the acute glucose challenge.

Lifestyle and Behavioral Interventions
Risk Determinants of Type 2 Diabetes Mellitus with Severe Obesity and Prediction Model for Diabetes Remission after Bariatric Metabolic Surgery: Zilong Wu, Yuxia Li, Dehui Wang, Bing Wu, Kaisheng Yuan, Yun Liu, Hao Zhu, Sijie Chen, Wah Yang, Ruixiang Hu, Cunchuan Wang; Received April 15, 2025 Accepted September 8, 2025 Published online November 25, 2025; DOI: https://doi.org/10.4093/dmj.2025.0337 [Epub ahead of print]

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Bariatric metabolic surgery (BMS) has been established as an effective intervention for obesity and type 2 diabetes mellitus (T2DM). However, systematic research addressing the onset of diabetes and post-surgical remission in severely obese populations remains scarce. This study aims to identify risk factors for T2DM in populations with severe obesity undergoing BMS and develop and validate a prediction model for the primary outcome of diabetes remission (DR) 1 year after BMS. This research provides a precise tool for managing T2DM in populations with severe obesity.
Methods
This research utilizes the China Obesity and Metabolic Surgery Database, retrospectively analyzing 3,670 severely obese populations who underwent BMS between January 2014 and January 2024. Differential analysis identified risk factors for T2DM onset, while univariate and multivariate regression analyses identified independent risk factors for DR post-surgery. A prediction model for DR was developed and internally validated.
Results
Factors associated with T2DM onset in severely obese populations included family history of diabetes, hypertension, hyperlipidemia, glycosylated hemoglobin (HbA1c) levels, and fasting plasma glucose. Independent factors influencing DR postsurgery included diabetes duration, surgical method, HbA1c, and insulin requirement. Subsequent model validation confirmed stable performance metrics (area under the curve values training, 0.71; validation, 0.72).
Conclusion
This study identifies risk factors for T2DM onset and a prediction model for DR following BMS in the Chinese severely obese population. It provides a more precise risk assessment tool for patients with severe obesity and T2DM, and lays the groundwork for future multicenter studies and international collaborations.

Basic and Translational Research
LRRFIP1 Inhibits White Adipocyte Differentiation by Suppressing the E2F6/C/EBPα Axis: Lei Zhou, Yuwen Jiao, Jiaming Xue, Xiaoqiang Zhan, Dongmei Wang, Liming Tang; Received March 4, 2025 Accepted July 24, 2025 Published online November 12, 2025; DOI: https://doi.org/10.4093/dmj.2025.0178 [Epub ahead of print]

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To investigate the biological functions of the transcription factor LRR binding FLII interacting protein 1 (LRRFIP1) in white adipocyte differentiation (WAD) and elucidate the underlying molecular regulatory mechanisms involved.
Methods
Consensus clustering, differential gene expression screening, and intersection analysis were used to identify transcription factors involved in WAD. Adipogenic differentiation experiments were conducted using C3H10T1/2 cells, and a diet-induced obesity model in C57BL/6J mice was established to investigate the function of LRRFIP1 in WAD in vitro and in vivo. Molecular mechanisms were examined through quantitative real-time polymerase chain reaction, Western blotting, luciferase assays, and chromatin immunoprecipitation.
Results
Bioinformatics analyses identified LRRFIP1 as a transcription factor associated with WAD. LRRFIP1 expression was downregulated in white adipose tissues from obese patients and in mature white adipocytes. Silencing LRRFIP1 significantly inhibited WAD in C3H10T1/2 cells and reduced differentiation biomarker expression; in contrast, overexpressing LRRFIP1 had the opposite effects. Mechanistically, LRRFIP1 bound to the E2F transcription factor 6 (E2F6) promoter to suppress E2F6 transcription, thereby downregulating a key differentiation regulator, CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, in a diet-induced obesity model, LRRFIP1 could regulate the differentiation and maturation of inguinal white adipose tissue.
Conclusion
Our findings reveal that LRRFIP1 plays a crucial inhibitory role in WAD by negatively regulating the E2F6/C/EBPα axis. This discovery not only enriches our understanding of the molecular networks governing WAD but also holds great promise for creating targeted therapies for obesity and associated metabolic conditions.

Cardiovascular Risk/Epidemiology
High Waist-to-Height Ratio Increases the Risk of Cardiovascular Outcomes in Adults with Type 1 Diabetes Mellitus: A Nationwide Cohort Study: Kyeong-Jin Kim, Seohyun Kim, Rosa Oh, So Hyun Cho, Myunghwa Jang, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Ji Yoon Kim, Jae Hyeon Kim; Received March 4, 2025 Accepted June 21, 2025 Published online September 4, 2025; DOI: https://doi.org/10.4093/dmj.2025.0179 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Central obesity contributes to an increased risk of cardiovascular disease (CVD) and mortality. The waist-to-height ratio (WHtR) is a practical marker of central obesity across sexes, ages, and ethnicities. However, its association with comprehensive cardiovascular (CV) outcomes in patients with type 1 diabetes mellitus (T1DM) remains unclear.
Methods
From a nationwide cohort database (2006–2020), 16,928 Korean adults with T1DM were included. Participants were categorized by their WHtR values using three criteria: a three-group classification (<0.5, 0.5 to <0.6, and ≥0.6) and two binary classifications (≥0.5 vs. <0.5; ≥0.6 vs. <0.6). The primary outcomes were composite CV events, including heart failure (HF), myocardial infarction (MI), ischemic stroke, and CVD-related deaths, with each component analyzed as a secondary outcome.
Results
During a median follow-up of 6.7 years (interquartile range, 5.2 to 8.8), 4,293 composite CV events occurred. Compared to the WHtR <0.5 group, the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the composite CV outcome were 1.14 (1.05 to 1.24) in the WHtR 0.5 to <0.6 group and 1.62 (1.38 to 1.90) in the WHtR ≥0.6 group (P for trend <0.001). Increasing trends in aHRs were noted with rising WHtR values for each component of the composite outcome. Compared to the WHtR <0.6 group, the aHRs for the WHtR ≥0.6 group were as follows: HF, 1.49 (95% CI, 1.28 to 1.73); MI, 1.31 (95% CI, 1.02 to 1.68); ischemic stroke, 1.24 (95% CI, 1.02 to 1.51); and CVD-related death, 2.09 (95% CI, 1.49 to 2.92).
Conclusion
High WHtR is associated with an increased risk of CV events in adults with T1DM.

Others
Dynamic Lipidomic Remodeling and Clinical Correlations after Sleeve Gastrectomy in Obese Subjects: Gakyung Lee, Yeong Chan Lee, Minkuk Park, Seong Min Kim, Ji-Hyeon Park, Dae Ho Lee; Received February 12, 2025 Accepted April 17, 2025 Published online August 14, 2025; DOI: https://doi.org/10.4093/dmj.2025.0120 [Epub ahead of print]

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Background
Sleeve gastrectomy (SG) is an effective and the most commonly performed surgical intervention for obesity. However, detailed studies on the underlying mechanisms, particularly those involving lipid metabolism, remain limited. This study aimed to identify novel pathways associated with the metabolic efficacy of SG by assessing alterations in the serum lipidomic profiles of obese subjects following surgery.
Methods
A prospective study of 50 obese participants undergoing laparoscopic SG was conducted at a tertiary medical center. Serum samples were collected before surgery and 6 months after SG. Lipidomic profiling was performed alongside comprehensive follow-up assessments. Statistical analyses explored lipidomic alterations and their correlations with changes in clinical parameters (Clinical trial registration No. KCT0003527 and KCT0009704).
Results
Participants experienced a 25% reduction in body weight 6 months after SG, with a marked reduction (>70%) in hepatic steatosis and insulin resistance, and a 2-fold increase in plasma oxyntomodulin levels. Lipidomic analysis revealed significant molecular shifts in lipid subclasses based on the fatty acyl composition of lipid species, showing a trend toward higher unsaturation and longer carbon chain lengths, as well as metabolic regulation in specific lipid pathways. Key findings included characteristic shifts within triacylglycerols and glycerophospholipids, which were significantly associated with changes in oxyntomodulin levels. Enhanced phosphatidylcholine-to-lysophosphatidylcholine conversion and upregulated ether lipid levels correlated with liver stiffness measures. Metabolic remodeling of sphingolipids—characterized by a decrease in ceramide/sphingomyelin levels and upregulation of the hexosylceramide pathway—emerged as an additional lipidomic signature after SG.
Conclusion
These findings highlight the complex lipidomic remodeling underlying the metabolic efficacy and therapeutic potential of SG.

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Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications
Xuan Trong Truong, Dae Ho Lee
Diabetes & Metabolism Journal.2025; 49(5): 964. CrossRef

Basic and Translational Research
Construction of a Novel Secreted Protein Database and Identification of a New Adipokine CRELD2: Shu-Na Wang, Zhi-Yong Li, Qi-Sheng Ling, Peng-Fei Jing, Wen-Yu Liu, Yi-Jie Zhang, Xiu-Ping Zhang, Xi-Yuan Wang, Fu-Qiang Chang, Zhu-Wei Miao, Jing-Xin Zhao, Jin Chen, Chao-Yu Miao; Diabetes Metab J. 2025;49(5):1006-1023. Published online July 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0211

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Abstract PDF Supplementary Material PubReader ePub: Background
Secreted proteins may become therapeutic targets, drugs and biomarkers for aging and disease. This study aimed to establish a novel secreted protein database for adipose tissue under access to food ad libitum (AL) and caloric restriction (CR), and verify a novel adipokine.
Methods
Twelve rat chips were used for whole-genome expression in various adipose tissues from AL and CR rats, followed by bioinformatics analysis and experiments in mice, rats, and humans as well as in obesity and diabetes models.
Results
Adipose tissue expression profiles in rat different locations exhibited unique features, and enrichment analysis of differentially expressed genes between CR and AL groups showed CR effects on different adipose tissues. The 1,472 putative secreted proteins were identified, in which 200 genes were highly expressed, constructing a potential adipokines library. Cysteine rich with EGF like domains 2 (CRELD2, also named MESFATIN), whose gene was mesenteric adipose tissue specifically expressed and upregulated by CR in rat chips, was selected and verified as novel adipokine with proving its expression and secretion in in vivo mouse, rat and human and in vitro adipose tissue and adipocyte. CRELD2 secretion increased during adipocyte differentiation, and CRELD2 recombinant protein promoted adipogenesis. Although CRELD2 serum concentration showed no difference between wild-type mice and genetic ob/ob obesity mice or high fat diet induced obesity mice, CRELD2 expression decreased in white adipose tissues of ob/ob mice.
Conclusion
CRELD2 is a new adipokine involved in adipocyte differentiation and adipogenesis. A novel secreted protein database created from multiple adipose depots with CR intervention is helpful for future discovery and research of more secreted proteins.

Review

Others
Differences between Type 2 Diabetes Mellitus and Obesity Management: Medical, Social, and Public Health Perspectives: Soo Lim, Ga Eun Nam, Arya M. Sharma; Diabetes Metab J. 2025;49(4):565-579. Published online June 11, 2025; DOI: https://doi.org/10.4093/dmj.2025.0278

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Obesity and type 2 diabetes mellitus (T2DM) are among the most urgent global public health challenges, yet differ markedly in recognition and management across medical, social, infrastructure, and policy domains. T2DM is supported by clear diagnostic criteria, defined treatment targets, and broad acceptance as a chronic disease. In contrast, obesity is assessed using imprecise metrics like body mass index, lacks standardized treatment goals, and is often misunderstood as a lifestyle issue rather than a chronic, relapsing disease. This misconception contributes to stigma, discrimination, and unrealistic patient expectations. T2DM receives substantial research funding, comprehensive clinical guidelines, and structured medical education, with strong support from large professional societies and multidisciplinary care models. Obesity care remains underfunded, inconsistently delivered, and underrepresented in medical training. Public health and policy efforts strongly favor T2DM, providing coordinated programs, insurance coverage, and regulatory oversight. Conversely, obesity is marginalized, with limited policy influence and a largely unregulated commercial weight-loss industry. Bridging these disparities requires adopting lessons from T2DM management—such as evidence-based guidelines, improved provider training, expanded insurance coverage, and public health strategies—to enhance obesity care and recognize it as a chronic disease requiring long-term, structured management.

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GLP-1 Receptor Agonists: Advances in Mechanism, Therapeutic Applications, and Future Perspectives
Megha Pawar, Chandrashekhar Patil, Zubershaha Fakir, Durgesh Pagar, Sunil Mahajan
BioMed Target Journal.2025; : 2. CrossRef

Original Articles

Basic and Translational Research
Serpina3c Mitigates Adipose Tissue Inflammation by Inhibiting the HIF1α-Mediated Endoplasmic Reticulum Overoxidation in Adipocytes: Yu Jiang, Jia-Qi Guo, Ya Wu, Peng Zheng, Shao-Fan Wang, Meng-Chen Yang, Gen-Shan Ma, Yu-Yu Yao; Diabetes Metab J. 2026;50(1):62-76. Published online May 22, 2025; DOI: https://doi.org/10.4093/dmj.2024.0441

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Abstract PDF Supplementary Material PubReader ePub: Background
Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity.
Methods
Wild type and Serpina3c knockout (Serpina3c^–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c^–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes.
Results
Serpina3c^–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation.
Conclusion
These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Basic and Translational Research
Phosphodiesterase 5 Inhibitor Improves Insulin Sensitivity by Regulating Adipose Tissue Macrophage Polarization in Diet-Induced Obese Mice: Dan-Gyeong Song, Seongwon Pak, Dae-Chul Shin, Shindy Soedono, Kae Won Cho, Yejin Park, Subin Moon, Sooyeon Jang, Saeha Kim, Sang-Won Han, Keunwook Lee, Jong-Hee Sohn, Chan Hee Lee; Received June 14, 2024 Accepted February 25, 2025 Published online May 22, 2025; DOI: https://doi.org/10.4093/dmj.2024.0308 [Epub ahead of print]

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Background
Obesity is a rapidly increasing global health issue, which is associated with glucose and insulin resistance. Phosphodiesterase type 5 (PDE5) inhibitors (PDE5i) are known for their ability to enhance blood flow and vascular stability and are widely used to treat conditions such as erectile dysfunction, pulmonary hypertension, heart failure, and cancer. However, studies investigating the role of PDE5i in alleviating obesity and metabolic diseases remains unclear. Therefore, we investigated the effects of PDE5i on obesity and metabolic disorders in diet-induced obese mice and its underlying mechanisms.
Methods
PDE5i was administered to high-fat diet (HFD)-fed C57BL/6J mice for 6 to 7 weeks. Body weight and food intake were measured weekly, and baseline metabolic rates, physical activity, and glucose and insulin tolerance tests were assessed during PDE5i administration. Macrophages and T-cells in the gonadal white adipose tissue (gWAT) were analyzed by flow cytometry. Vascular stability and blood flow in gWAT were analyzed via immunostaining and in vivo live imaging. RAW264.7 cells and bone marrow-derived macrophages were used to determine immunoregulatory effects of PDE5i.
Results
In HFD-fed mice, PDE5i administration significantly enhanced systemic insulin sensitivity and AKT phosphorylation in gWAT. PDE5i reduced the M1/M2 ratio of gWAT macrophages of obese mice. These phenomena were associated with enhanced blood flow to the gWAT. In vitro experiments revealed that PDE5i suppressed lipopolysaccharide-induced proinflammatory cytokine production and increased the mRNA expression of genes associated with M2 polarization.
Conclusion
PDE5i plays a role in regulating adipose tissue inflammation and thus holds promise as a therapeutic agent for metabolic enhancement.

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Beyond Cyclic Nucleotides: Emerging Roles of Phosphodiesterases in Metabolic Disorders
Nicole Bertani, Maria Rita Assenza, Francesca Sciarra, Giorgia D’Addato, Francesca Gioia Klinger, Mary Anna Venneri, Andrea M. Isidori, Federica Campolo
Frontiers in Bioscience-Landmark.2025;[Epub] CrossRef

Reviews

Basic and Translational Research
Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease: Joonyub Lee, Won Gun Choi, Marie Rhee, Seung-Hwan Lee; Diabetes Metab J. 2025;49(3):348-367. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0184

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Extracellular vesicles (EVs) are lipid bilayer-enclosed particles carrying bioactive cargo, including nucleic acids, proteins, and lipids, facilitating intercellular and interorgan communication. In addition to traditional mediators such as hormones, metabolites, and cytokines, increasing evidence suggests that EVs are key modulators in various physiological and pathological processes, particularly influencing metabolic homeostasis and contributing to the progression of cardiometabolic diseases. This review provides an overview of the most recent insights into EV-mediated mechanisms involved in the pathogenesis of obesity, insulin resistance, diabetes mellitus, steatotic liver disease, atherosclerosis, and cardiovascular disease. EVs play a critical role in modulating insulin sensitivity, glucose homeostasis, systemic inflammation, and vascular health by transferring functional molecules to target cells. Understanding the EV-mediated network offers potential for identifying novel biomarkers and therapeutic targets, providing opportunities for EV-based interventions in cardiometabolic disease management. Although many challenges remain, this evolving field highlights the need for further research into EV biology and its translational applications in cardiovascular and metabolic health.

Citations

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Alice Njolke Mafe, Javad Sharifi‐Rad, Daniela Calina, Ayobami Joshua Ogunyemi, Abiola O. Tubi
Food Frontiers.2026;[Epub] CrossRef
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Young-Sool Hah, Jeongyun Hwang, Seung-Jun Lee, Seung-Jin Kwag
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Milad Shahdkar, Mahdi Orang Goorabzarmakhi, Mahdi Shafizadeh, Farahnaz Joukar, Saman Maroufizadeh, Niloofar Faraji, Tahereh Zeinali, Fariborz Mansour-Ghanaei
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Charalampos Voros, Georgios Papadimas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria An
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European Journal of Medical Research.2025;[Epub] CrossRef
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International Journal of Molecular Sciences.2025; 26(22): 11052. CrossRef
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Basic and Translational Research
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies: Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi; Diabetes Metab J. 2025;49(3):333-347. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0106

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

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Original Articles

Basic and Translational Research
Macrophage-Specific Progranulin Deficiency Prevents Diet-Induced Obesity through the Inhibition of Hypothalamic and Adipose Tissue Inflammation: Chan Hee Lee, Chae Beom Park, Hyun-Kyong Kim, Won Hee Jang, Se Hee Min, Jae Bum Kim, Min-Seon Kim; Diabetes Metab J. 2025;49(4):784-797. Published online March 11, 2025; DOI: https://doi.org/10.4093/dmj.2024.0486

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Background
Chronic low-grade inflammation in multiple metabolic organs contributes to the development of insulin resistance induced by obesity. Progranulin (PGRN) is an evolutionarily-conserved secretory protein implicated in immune modulation. The generalized deletion of the PGRN-encoded Grn gene improves insulin resistance and glucose intolerance in obese mice fed a high-fat diet (HFD). However, it remains unclear which cells or organs are responsible for the beneficial metabolic effect of Grn depletion.
Methods
Considering the critical role of macrophages in HFD-induced obesity and inflammation, we generated mice with a macrophage-specific Grn depletion (Grn-MΦKO mice) by mating lysozyme M (LysM)-Cre and Grn-floxed mice. Body weight, food intake, energy expenditure, and glucose and insulin tolerance were compared between Grn-MΦKO mice and their wildtype (WT) controls under normal chow diet (NCD)- or HFD-fed conditions. We also examined macrophage activation and inflammation- related gene expression in the visceral adipose tissue and hypothalamus along with insulin and leptin signaling.
Results
Grn-MΦKO mice showed no alteration in metabolic phenotypes under NCD-fed conditions. However, upon HFD feeding, these mice exhibited less weight gain and improved glucose and insulin tolerance compared to WT mice. Moreover, HFD-induced macrophage activation and proinflammatory cytokine expression were significantly reduced in both the adipose tissue and hypothalamus of Grn-MΦKO mice, while HFD-induced impairments in leptin and insulin signaling showed improvement.
Conclusion
Macrophage-derived PGRN and possibly other Grn products play a critical role in the development of HFD-induced obesity, tissue inflammation, and impaired hormonal signaling in both central and peripheral metabolic organs.

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Tissue-specific immune and MAPK signatures in models of reduced Progranulin and Western diet
Andrea R. Merchak, Maria Elizabeth de Sousa Rodrigues, Cassandra Cole, Noelle Neighbarger, Nilay Bhavsar, Rebecca L. Wallings, Valerie Joers, Jianjun Chang, Sean D. Kelly, Timothy R. Sampson, Malú Gámez Tansey
Neurobiology of Disease.2026; 220: 107287. CrossRef
Role of Macrophage-Derived Progranulin in Energy and Glucose Metabolism
Do Kyeong Song
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The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Milton Packer
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Serum Granulin Concentrations Are Elevated in Prediabetes and Newly Diagnosed Diabetes: A Cross-Sectional Study
Yu-Hsuan Chou, Yuan Kao, Ka Chon Chan, Hsuan-Wen Chou, Yu-Cheng Liang, Hung-Tsung Wu, Horng-Yih Ou
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Guideline/Statement/Fact Sheet
Prevalence, Incidence, and Metabolic Characteristics of Young Adults with Type 2 Diabetes Mellitus in South Korea (2010–2020): Ji Yoon Kim, Jiyoon Lee, Joon Ho Moon, Se Eun Park, Seung-Hyun Ko, Sung Hee Choi, Nam Hoon Kim; Diabetes Metab J. 2025;49(2):172-182. Published online March 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0826

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Background
This study aimed to examine trends in the prevalence, incidence, metabolic characteristics, and management of type 2 diabetes mellitus (T2DM) among young adults in South Korea.
Methods
Young adults with T2DM were defined as individuals aged 19 to 39 years who met the diagnostic criteria for T2DM. Data from the Korean National Health Insurance Service-Customized Database (2010–2020, n=225,497–372,726) were analyzed to evaluate trends in T2DM prevalence, incidence, metabolic profiles, comorbidities, and antidiabetic drug prescription. Additional analyses were performed using the Korea National Health and Nutrition Examination Survey.
Results
The prevalence of T2DM in young adults significantly increased from 1.02% in 2010 to 2.02% in 2020 (P<0.001), corresponding to 372,726 patients in 2020. Over the same period, the incidence rate remained stable within the range of 0.36% to 0.45%. Prediabetes prevalence steadily increased from 15.53% to 20.92%, affecting 3.87 million individuals in 2020. The proportion of young adults with T2DM who were obese also increased, with 67.8% having a body mass index (BMI) ≥25 kg/m² and 31.6% having a BMI ≥30 kg/m² in 2020. The prevalence of hypertension, dyslipidemia, and fatty liver disease also increased, reaching 34.2%, 79.8%, and 78.9%, respectively, in 2020. Although the overall pharmacological treatment rate remained low, the prescription of antidiabetic medications with weight-reducing properties increased over the study period.
Conclusion
The prevalence of T2DM among young adults in South Korea nearly doubled over the past decade. The strong association with obesity and metabolic comorbidities emphasizes the urgent need for targeted prevention and management strategies tailored to this population.

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Association of temporal MASLD with type 2 diabetes, cardiovascular disease and mortality
Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park
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Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
Ji Yoon Kim, Nam Hoon Kim, Jiyoon Lee, Dong-Hoon Kim, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef
Young Adults at Risk: Tackling the Surge of Early‑Onset Type 2 Diabetes in Korea
Eun-Hee Cho
Endocrinology and Metabolism.2025; 40(4): 542. CrossRef
Young patients with type 2 diabetes have high relative risks for complications in a country with middle-high sociodemographic index, similarly to those countries with high index
Gergő A. Molnár, Zoltán Kiss, István Wittmann
Frontiers in Endocrinology.2025;[Epub] CrossRef
Cost-Effectiveness Analysis of Real-Time Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in People With Type 2 Diabetes Treated With Non-Intensive Insulin Therapy in South Korea
Ji Yoon Kim, Sabrina Ilham, Hamza Alshannaq, Richard F. Pollock, Martin Field, Gregory J. Norman, Sang-Man Jin, Jae Hyeon Kim
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Can screening for albuminuria detect type 2 diabetes mellitus?
Mi Kyung Kim
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Association between severe acute pancreatitis and new-onset diabetes: a propensity score-matched real-world study
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Frontiers in Endocrinology.2025;[Epub] CrossRef

Metabolic Risk/Epidemiology
Trends in Metabolically Unhealthy Obesity by Age, Sex, Race/Ethnicity, and Income among United States Adults, 1999 to 2018: Wen Zeng, Weijiao Zhou, Junlan Pu, Juan Li, Xiao Hu, Yuanrong Yao, Shaomei Shang; Diabetes Metab J. 2025;49(3):475-484. Published online February 25, 2025; DOI: https://doi.org/10.4093/dmj.2024.0364

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Background
This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018.
Methods
We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m² with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO.
Results
The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups.
Conclusion
This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

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Repercussions of racial, gender, and class inequities on food and nutrition conditions: Implications for public health
Tatiana Palotta Minari
Nutrition.2026; 142: 112995. CrossRef
Addressing the Persistent Increase and Inequities in Metabolically Unhealthy Obesity: Toward an Understanding of Clinical Obesity
Young Sang Lyu, Sang Yong Kim
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Cross-national comparison of metabolic syndrome prevalence and related medication use in South Korea and the United States, 2007–2020: Evidence from KHANES and NHANES
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Cardiovascular Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study: Honglin Sun, Zhenyu Wu, Guang Wang, Jia Liu; Diabetes Metab J. 2025;49(3):448-461. Published online January 20, 2025; DOI: https://doi.org/10.4093/dmj.2024.0100

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Background
Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort.
Methods
This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed.
Results
During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders.
Conclusion
High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

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Normalized creatinine-to-cystatin C ratio and cardiovascular disease risk in populations with cardiovascular–kidney–metabolic syndrome stages 0–3: findings from a national and prospective cohort study
Defei Chen, Yuhui Li, Tailin Ran, Fu Song, Zheng Yang, Weilin Tan, Qiuyi Lu, Lanxin Tang, Lining Yang, Dingqun Bai
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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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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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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.

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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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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.

Citations

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Epidemiology and characteristics of obesity in Koreans based on the 2024 Obesity Fact Sheet
Eun-Jung Rhee
Journal of the Korean Medical Association.2026; 69(1): 4. CrossRef
Age at Menopause and Development of Type 2 Diabetes in Korea
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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.

Citations

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Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models
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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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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.

Citations

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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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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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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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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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Original Articles

Complication
Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial: Daniel Nyarko Hukportie, Fu-Rong Li, Rui Zhou, Jia-Zhen Zheng, Xiao-Xiang Wu, Xian-Bo Wu; Diabetes Metab J. 2022;46(5):767-780. Published online May 10, 2022; DOI: https://doi.org/10.4093/dmj.2021.0258

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Background
Obesity is associated with adverse health events among diabetic patients, however, the relationship between obesity fluctuation and risk of microvascular complications among this specific population is unclear. We aimed to examine the effect of waist circumference (WC) and body mass index (BMI) variability on the risk of diabetic microvascular outcome
Methods
Annually recorded anthropometric data in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was used to examine the association of WC and BMI variability defined as variability independent of mean, with the risk of microvascular outcomes, including neuropathy, nephropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) (Trial registration: ClinicalTrials.gov., no. NCT00000620).
Results
There were 4,031, 5,369, and 2,601 cases of neuropathy, nephropathy, and retinopathy during a follow-up period of 22,524, 23,941, and 23,850 person-years, respectively. Higher levels of WC and BMI variability were associated with an increased risk of neuropathy. Compared with the lowest quartile, the fully-adjusted HR (95% CI) for the highest quartile of WC and BMI variability for neuropathy risk were 1.21 (1.05 to 1.40) and 1.16 (1.00 to 1.33), respectively. Also, higher quartiles of BMI variability but not WC variability were associated with increased risk of nephropathic events. The fully-adjusted HR (95% CI) for the highest quartile compared with the lowest quartile of BMI variability was 1.31 (1.18 to 1.46). However, the results for retinopathic events were all insignificant.
Conclusion
Among participants with type 2 diabetes mellitus, WC and BMI variability were associated with a higher risk of neuropathic events, whereas BMI variability was associated with an increased risk of nephropathic events.

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Drug/Regimen
Effect of Lactobacillus plantarum LMT1-48 on Body Fat in Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial: Minji Sohn, Hyeyoung Jung, Woo Shun Lee, Tai Hoon Kim, Soo Lim; Diabetes Metab J. 2023;47(1):92-103. Published online April 29, 2022; DOI: https://doi.org/10.4093/dmj.2021.0370

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Background
We investigated whether Lactobacillus plantarum strain LMT1-48, isolated from Korean fermented foods and newborn feces, is a suitable probiotic supplement to treat overweight subjects.
Methods
In this randomized, double-blind, placebo-controlled clinical trial, 100 volunteers with a body mass index of 25 to 30 kg/m² were assigned randomly (1:1) to receive 2×10¹⁰ colony forming units of LMT1-48 or to a placebo treatment group. Body composition was measured by dual-energy X-ray absorptiometry, and abdominal visceral fat area (VFA) and subcutaneous fat area were measured by computed tomography scanning. Changes in body fat, VFA, anthropometric parameters, and biomarkers were compared between the two treatment groups (ClinicalTrials.gov number: NCT03759743).
Results
After 12 weeks of treatment, the body weight decreased significantly from 76.6±9.4 to 75.7±9.2 kg in the LMT1-48 group but did not change in the placebo group (P=0.022 between groups). A similar pattern was found in abdominal VFA between the two groups (P=0.041). Serum insulin levels, the corresponding homeostasis model assessment of insulin resistance, and leptin levels decreased in the LMT1-48 group but increased in the placebo group (all P<0.05). Decrease in body weight and body mass index by treatment with LMT1-48 was correlated with increase in Lactobacillus levels significantly. LMT1-48 also increased Oscillibacter levels significantly, which were negatively correlated with triglyceride and alanine transaminase levels.
Conclusion
Administration of LMT1-48 decreased body weight, abdominal VFA, insulin resistance, and leptin levels in these subjects with overweight, suggesting its anti-obesogenic therapeutic potential.

Citations

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Metabolic Risk/Epidemiology
Associations between Weight-Adjusted Waist Index and Abdominal Fat and Muscle Mass: Multi-Ethnic Study of Atherosclerosis: Ji Yoon Kim, Jimi Choi, Chantal A. Vella, Michael H. Criqui, Matthew A. Allison, Nam Hoon Kim; Diabetes Metab J. 2022;46(5):747-755. Published online March 30, 2022; DOI: https://doi.org/10.4093/dmj.2021.0294

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336 Download
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Background
The weight-adjusted waist index (WWI) reflected body compositional changes with aging. This study was to investigate the association of WWI with abdominal fat and muscle mass in a diverse race/ethnic population.
Methods
Computed tomography (CT) data from 1,946 participants for abdominal fat and muscle areas from the Multi-Ethnic Study of Atherosclerosis (785 Whites, 252 Asians, 406 African American, and 503 Hispanics) were used. Among them, 595 participants underwent repeated CT. The WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). The associations of WWI with abdominal fat and muscle measures were examined, and longitudinal changes in abdominal composition measures were compared.
Results
In all race/ethnic groups, WWI was positively correlated with total abdominal fat area (TFA), subcutaneous fat area, and visceral fat area, but negatively correlated with total abdominal muscle area (TMA) and abdominal muscle radiodensity (P<0.001 for all). WWI showed a linear increase with aging regardless of race and there were no significant differences in the WWI distribution between Whites, Asians, and African Americans. In longitudinal analyses, over 38.6 months of follow-up, all abdominal fat measures increased but muscle measures decreased, along with increase in WWI. The more the WWI increased, the more the TFA increased and the more the TMA decreased.
Conclusion
WWI showed positive associations with abdominal fat mass and negative associations with abdominal muscle mass, which likely reflects the abdominal compositional changes with aging in a multi-ethnic population.

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Diabetes, Obesity and Metabolism.2025; 27(8): 4248. CrossRef
Association between weight-adjusted-waist index and anxiety among adults in the National Health and Nutrition Examination Survey (NHANES), 2007–2012
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Frontiers in Nutrition.2025;[Epub] CrossRef
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Frontiers in Public Health.2025;[Epub] CrossRef
Hypertension mediates the association between weight-adjusted waist index and new onset stroke risk in middle-aged and older Chinese adults: evidence from the CHARLS study
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Frontiers in Neurology.2025;[Epub] CrossRef
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Annals of Medicine.2025;[Epub] CrossRef
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Frontiers in Nutrition.2025;[Epub] CrossRef
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Risk Management and Healthcare Policy.2025; Volume 18: 2387. CrossRef
Association between carotenoids and weight-adjusted waist index a cross-sectional study based on the national health and nutrition examination survey 2017–2018
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Obesity Research & Clinical Practice.2025; 19(4): 283. CrossRef
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Triglyceride glucose-weight-adjusted waist index as a cardiovascular mortality predictor: incremental value beyond the establishment of TyG-related indices
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BMC Public Health.2025;[Epub] CrossRef
The novel triglyceride‒glucose-weighted adjusted waist index as a supplementary diagnostic tool for heart failure: evidence of improved reclassification beyond traditional TyG-related indices from a cross-sectional study
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Cardiovascular Diabetology.2025;[Epub] CrossRef
Independent association of weight-adjusted waist index with asthma in U.S. adolescents: Mediating roles of eosinophil percentage, total cholesterol, and HDL cholesterol
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PLOS One.2025; 20(7): e0328796. CrossRef
Association between the weight-adjusted waist index and type 2 diabetes mellitus: Evidence from the RaNCD study
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Weight adjusted waist index is a superior obesity index for predicting arterial stiffness in type 2 diabetes mellitus
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Scientific Reports.2025;[Epub] CrossRef
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The American Journal of Clinical Nutrition.2025; 122(5): 1432. CrossRef
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Medicine.2025; 104(41): e45110. CrossRef
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PLOS One.2025; 20(10): e0334922. CrossRef
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Cardiorenal Medicine.2025; 15(1): 572. CrossRef
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Journal of Affective Disorders.2024; 347: 299. CrossRef
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Frontiers in Endocrinology.2024;[Epub] CrossRef
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Journal of Affective Disorders.2024; 350: 49. CrossRef
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PLOS ONE.2024; 19(5): e0302137. CrossRef
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BMC Endocrine Disorders.2024;[Epub] CrossRef
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Association between weight-adjusted-waist index and depression in US adults: A cross-sectional study
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Frontiers in Endocrinology.2024;[Epub] CrossRef
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Frontiers in Endocrinology.2024;[Epub] CrossRef
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Frontiers in Endocrinology.2024;[Epub] CrossRef
Can weight-adjusted waist circumference index become a single anthropometric predictor of prostate-specific antigen concentration? A National Health and Nutrition Examination Survey analysis (2003–2010)
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Journal of Investigative Medicine.2024; 72(6): 532. CrossRef
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Scientific Reports.2024;[Epub] CrossRef
Weight-adjusted waist index is an independent predictor of all-cause and cause-specific mortality in patients with asthma
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Heart & Lung.2024; 68: 166. CrossRef
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Diabetes, Obesity and Metabolism.2024; 26(9): 4069. CrossRef
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Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(9): 2095. CrossRef
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Frontiers in Nutrition.2024;[Epub] CrossRef
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European Journal of Medical Research.2024;[Epub] CrossRef
The association between weight-adjusted waist circumference index and cardiovascular disease and mortality in patients with diabetes
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Scientific Reports.2024;[Epub] CrossRef
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Frontiers in Public Health.2024;[Epub] CrossRef
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Journal of Orthopaedic Surgery.2024;[Epub] CrossRef
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BMC Public Health.2024;[Epub] CrossRef
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EPMA Journal.2024; 15(3): 491. CrossRef
The Link Between Weight-Adjusted-Waist Index and Psoriasis in Adults: A Cross-Sectional Study Based on 2009-2014 and 2003-2006 Data
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Clinical, Cosmetic and Investigational Dermatology.2024; Volume 17: 1763. CrossRef
Association of weight-adjusted waist index with cardiovascular disease and mortality among metabolic syndrome population
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Scientific Reports.2024;[Epub] CrossRef
Association between the weight-adjusted-waist index and circadian syndrome in findings from a nationwide study
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Scientific Reports.2024;[Epub] CrossRef
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Journal of Orthopaedic Surgery and Research.2024;[Epub] CrossRef
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Diabetes, Obesity and Metabolism.2024; 26(12): 5621. CrossRef
Is weight-adjusted waist index more strongly associated with diabetes than body mass index and waist circumference?: Results from the database large community sample study
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PLOS ONE.2024; 19(9): e0309150. CrossRef
Weight-adjusted waist index predicts metabolic syndrome in Caucasian patients with obesity
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BMC Geriatrics.2024;[Epub] CrossRef
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Frontiers in Endocrinology.2024;[Epub] CrossRef
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BMC Public Health.2024;[Epub] CrossRef
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Scientific Reports.2024;[Epub] CrossRef
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Scientific Reports.2024;[Epub] CrossRef
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Scientific Reports.2024;[Epub] CrossRef
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Frontiers in Medicine.2024;[Epub] CrossRef
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BMC Psychiatry.2024;[Epub] CrossRef
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PLOS ONE.2024; 19(11): e0313625. CrossRef
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Scientific Reports.2024;[Epub] CrossRef
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Archives of Public Health.2024;[Epub] CrossRef
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Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 4235. CrossRef
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Frontiers in Cardiovascular Medicine.2024;[Epub] CrossRef
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Nature and Science of Sleep.2024; Volume 16: 1779. CrossRef
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Frontiers in Cardiovascular Medicine.2024;[Epub] CrossRef
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Scientific Reports.2024;[Epub] CrossRef
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Frontiers in Endocrinology.2023;[Epub] CrossRef
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Frontiers in Endocrinology.2023;[Epub] CrossRef
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European Journal of Medical Research.2023;[Epub] CrossRef
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BMC Cardiovascular Disorders.2023;[Epub] CrossRef
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Associations between weight-adjusted-waist index and infertility: Results from NHANES 2013 to 2020
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Scientific Reports.2022;[Epub] CrossRef

Brief Report

Metabolic Risk/Epidemiology
Trends in the Prevalence of Obesity and Its Phenotypes Based on the Korea National Health and Nutrition Examination Survey from 2007 to 2017 in Korea: Sang Ouk Chin, You-Cheol Hwang, Hong-Yup Ahn, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung; Diabetes Metab J. 2022;46(5):808-812. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0226

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This study used data from the Korea National Health and Nutrition Examination Survey IV–VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (β=0.326, P trend <0.01) between 2007 and 2017, and especially in men (β=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (β=0.565, P trend <0.01), while that of MHO increased only in women (β=0.179, P<0.05), especially in the younger age group (β=0.308, P<0.01).

Citations

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Korean Journal of Community Nutrition.2025; 30(2): 127. CrossRef
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Sung-Bin Hong, Ji-Eun Kim, Seung Seok Han, Joseph J. Shearer, Jungnam Joo, Ji-Yeob Choi, Véronique L. Roger
Epidemiology and Health.2025; 47: e2025005. CrossRef
Clinical and Humanistic Burden of Adult Obesity in Asia–Pacific: A Systematic Literature Review
Esther Artime, Sarah Zimner-Rapuch, Roger Chen, Qiuhe Ji, Ichiro Tatsuno, Rachel S. Newson, Tomotaka Shingaki, Si Si, Rachel Kewley, Sam Riley, Swarna Khare
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Metabolic Syndrome and Related Disorders.2022; 20(10): 551. CrossRef

Short Communication

Metabolic Risk/Epidemiology
Influence of Pre-Pregnancy Underweight Body Mass Index on Fetal Abdominal Circumference, Estimated Weight, and Pregnancy Outcomes in Gestational Diabetes Mellitus: Minji Kim, Kyu-Yeon Hur, Suk-Joo Choi, Soo-Young Oh, Cheong-Rae Roh; Diabetes Metab J. 2022;46(3):499-505. Published online January 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0059

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This study aimed to determine the influence of pre-pregnancy body mass index on pregnancy outcomes in gestational diabetes mellitus (GDM), comparing underweight patients with GDM with normal weight patients with GDM. Maternal baseline characteristics, ultrasonographic results, and pregnancy and neonatal outcomes were reviewed in 946 women with GDM with singleton pregnancies. Underweight patients with GDM showed a benign course in most aspects during pregnancy, except for developing a higher risk of giving birth to small for gestational age neonates. Underweight women with GDM required less insulin treatment, had a higher rate of vaginal delivery, and had a lower rate of cesarean delivery. In addition, their neonates were more likely to have fetal abdominal circumference and estimated fetal weight below the 10th percentile both at the time of GDM diagnosis and before delivery. Notably, their risk for preeclampsia and macrosomia were lower. Collectively, our data suggest that underweight women with GDM may require a different approach in terms of diagnosis and management throughout their pregnancy.

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Yoo Jinie Kim, Jinyoung Shin, Tae-Eun Kim, Sanghyun Park, Ran Lee, Yong Mean Park, Hye Won Park
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Hanbing Li, Zhixuan Xiang, Hui Li, Chenxi Xie, Zeng Li, Yingni Liang, Lingling Gao, Zhongyu Li
BMC Pregnancy and Childbirth.2025;[Epub] CrossRef
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Rija Siddiqui, Carrie J McAdams
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Pradnyashree Wadivkar, Meredith Hawkins
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Obesity Is Associated With Higher Risk of Adverse Maternal and Neonatal Outcomes Than Supervised Gestational Diabetes
Namju Seo, You Min Lee, Ye-jin Kim, Ji-hee Sung, Kyu-Yeon Hur, Suk-Joo Choi, Cheong-Rae Roh, Soo-young Oh
Journal of Korean Medical Science.2023;[Epub] CrossRef
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Honglin Sun, Yibo Zhou, Jia Liu, Ying Wang, Guang Wang
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef

Original Article

Metabolic Risk/Epidemiology
Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population: Min Jin Lee, Ah Reum Khang, Yang Ho Kang, Mi Sook Yun, Dongwon Yi; Diabetes Metab J. 2022;46(5):756-766. Published online January 20, 2022; DOI: https://doi.org/10.4093/dmj.2021.0166

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Background
The present study investigated the role of synergistic interaction between hyperuricemia and abdominal obesity as a risk factor for the components of metabolic syndrome.
Methods
We performed a cross-sectional study using the data of 16,094 individuals from the seventh Korean National Health and Nutrition Examination Survey (2016 to 2018). The adjusted odds ratios of metabolic syndrome and its components were analyzed by multivariate logistic regression analysis. The presence of synergistic interaction between hyperuricemia and abdominal obesity was evaluated by calculating the additive scales—the relative excess risk due to interaction, attributable proportion due to interaction, and synergy index (SI).
Results
There was a synergistic interaction between hyperuricemia and abdominal obesity in hypertriglyceridemia (men: SI, 1.39; 95% confidence interval [CI], 1.01 to 1.98; women: SI, 1.61; 95% CI, 1.02 to 2.69), and low high-density lipoprotein cholesterol (HDL-C) (men: SI, 2.03; 95% CI, 1.41 to 2.91; women: SI, 1.70; 95% CI, 1.05 to 2.95). There was no significant synergistic interaction between hyperuricemia and abdominal obesity for the risk of high blood pressure (men: SI, 1.22; 95% CI, 0.85 to 1.77; women: SI, 1.53; 95% CI, 0.79 to 2.97), and hyperglycemia (men: SI, 1.03; 95% CI, 0.72 to 1.47; women: SI, 1.39; 95% CI, 0.75 to 2.57).
Conclusion
Hyperuricemia and abdominal obesity synergistically increased the risk of hypertriglyceridemia and low HDL-C in both sexes.

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Hongwei Liu, Gaiying Ma, Jing Shi, Minheng Zhang, Fei Xu, Miaomiao Hou
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Review

Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression: Dae-Seok Kim, Philipp E. Scherer; Diabetes Metab J. 2021;45(6):799-812. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0077

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Graphical Abstract Abstract PDF PubReader ePub

Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Original Articles

Basic Research
The Effects of Exercise and Restriction of Sugar-Sweetened Beverages on Muscle Function and Autophagy Regulation in High-Fat High-Sucrose-Fed Obesity Mice: Didi Zhang, Ji Hyun Lee, Hyung Eun Shin, Seong Eun Kwak, Jun Hyun Bae, Liang Tang, Wook Song; Diabetes Metab J. 2021;45(5):773-786. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0157

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Background
Autophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training.
Methods
Obese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively.
Results
SR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group.
Conclusion
SR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.

Citations

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Basic Research
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway: Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha; Diabetes Metab J. 2021;45(6):921-932. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0187

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Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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Reviews

Drug/Regimen
Comprehensive Review of Current and Upcoming Anti-Obesity Drugs: Jang Won Son, Sungrae Kim; Diabetes Metab J. 2020;44(6):802-818. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0258

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Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

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Technology/Device
Present and Future of Digital Health in Diabetes and Metabolic Disease: Sang Youl Rhee, Chiweon Kim, Dong Wook Shin, Steven R. Steinhubl; Diabetes Metab J. 2020;44(6):819-827. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0088

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Abstract PDF PubReader ePub

The use of information and communication technology (ICT) in medical and healthcare services goes beyond everyday life. Expectations of a new medical environment, not previously experienced by ICT, exist in the near future. In particular, chronic metabolic diseases such as diabetes and obesity, have a high prevalence and high social and economic burden. In addition, the continuous evaluation and monitoring of daily life is important for effective treatment and management. Therefore, the wide use of ICTbased digital health systems is required for the treatment and management of these diseases. In this article, we compiled a variety of digital health technologies introduced to date in the field of diabetes and metabolic diseases.

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Original Articles

Cardiovascular Risk/Epidemiology
Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population: Heesun Lee, Hyo Eun Park, Ji Won Yoon, Su-Yeon Choi; Diabetes Metab J. 2021;45(2):219-230. Published online October 28, 2020; DOI: https://doi.org/10.4093/dmj.2019.0161; Correction in: Diabetes Metab J 2021;45(6):974

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300 Download
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Background
Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression.
Methods
This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units.
Results
During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m², increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators.
Conclusion
Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

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Metabolic Risk/Epidemiology
Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes: Hyun-Woong Cho, Wankyo Chung, Shinje Moon, Ohk-Hyun Ryu, Min Kyung Kim, Jun Goo Kang; Diabetes Metab J. 2021;45(2):209-218. Published online July 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0223

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Background

This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes.

Methods

We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index <7 kg/m² in men and <5.5kg/m² in women. A multivariate logistic regression analysis was performed to evaluate the odds ratio (OR) of sarcopenia and ABSI for CVD events according to the obesity phenotype.

Results

The MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile.

Conclusion

These results suggest that clinical approaches that consider muscle and body shape are required.

Citations

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Basic Research
Vimentin Deficiency Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice: SeoYeon Kim, Inyeong Kim, Wonkyoung Cho, Goo Taeg Oh, Young Mi Park; Diabetes Metab J. 2021;45(1):97-108. Published online June 15, 2020; DOI: https://doi.org/10.4093/dmj.2019.0198

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

Background

Obesity and type 2 diabetes mellitus are world-wide health problems, and lack of understanding of their linking mechanism is one reason for limited treatment options. We determined if genetic deletion of vimentin, a type 3 intermediate filament, affects obesity and type 2 diabetes mellitus.

Methods

We fed vimentin-null (Vim^−/−) mice and wild-type mice a high-fat diet (HFD) for 10 weeks and measured weight change, adiposity, blood lipids, and glucose. We performed intraperitoneal glucose tolerance tests and measured CD36, a major fatty acid translocase, and glucose transporter type 4 (GLUT4) in adipocytes from both groups of mice.

Results

Vim^−/− mice fed an HFD showed less weight gain, less adiposity, improved glucose tolerance, and lower serum level of fasting glucose. However, serum triglyceride and non-esterified fatty acid levels were higher in Vim^−/− mice than in wild-type mice. Vimentin-null adipocytes showed 41.1% less CD36 on plasma membranes, 27% less uptake of fatty acids, and 50.3% less GLUT4, suggesting defects in intracellular trafficking of these molecules.

Conclusion

We concluded that vimentin deficiency prevents obesity and insulin resistance in mice fed an HFD and suggest vimentin as a central mediator linking obesity and type 2 diabetes mellitus.

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Review

Basic Research
Consequences of Obesity on the Sense of Taste: Taste Buds as Treatment Targets?: Kerstin Rohde, Imke Schamarek, Matthias Blüher; Diabetes Metab J. 2020;44(4):509-528. Published online May 11, 2020; DOI: https://doi.org/10.4093/dmj.2020.0058

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Premature obesity-related mortality is caused by cardiovascular and pulmonary diseases, type 2 diabetes mellitus, physical disabilities, osteoarthritis, and certain types of cancer. Obesity is caused by a positive energy balance due to hyper-caloric nutrition, low physical activity, and energy expenditure. Overeating is partially driven by impaired homeostatic feedback of the peripheral energy status in obesity. However, food with its different qualities is a key driver for the reward driven hedonic feeding with tremendous consequences on calorie consumption. In addition to visual and olfactory cues, taste buds of the oral cavity process the earliest signals which affect the regulation of food intake, appetite and satiety. Therefore, taste buds may play a crucial role how food related signals are transmitted to the brain, particularly in priming the body for digestion during the cephalic phase. Indeed, obesity development is associated with a significant reduction in taste buds. Impaired taste bud sensitivity may play a causal role in the pathophysiology of obesity in children and adolescents. In addition, genetic variation in taste receptors has been linked to body weight regulation. This review discusses the importance of taste buds as contributing factors in the development of obesity and how obesity may affect the sense of taste, alterations in food preferences and eating behavior.

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Original Articles

Cardiovascular Risk/Epidemiology
Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults: Eun-Jung Rhee, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Won-Young Lee; Diabetes Metab J. 2020;44(4):592-601. Published online April 20, 2020; DOI: https://doi.org/10.4093/dmj.2019.0104; Correction in: Diabetes Metab J 2020;44(5):783

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173 Download
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Abstract PDF Supplementary Material PubReader ePub

Background

Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.

Methods

We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.

Results

Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.

Conclusion

Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.

Citations

Citations to this article as recorded by

Combined effects of glycemic status and adiposity on cardiovascular risk in chronic kidney disease: A nationwide population-based study
Eun Hui Bae, Sang Yup Lim, Bong Seong Kim, Kyungdo Han, Sang Heon Suh, Hong Sang Choi, Eun Mi Yang, Chang Seong Kim, Seong Kwon Ma, Soo Wan Kim
World Journal of Diabetes.2026;[Epub] CrossRef
Correlation Between Prognostic Nutritional Index and Heart Failure in Adults with Diabetes in the United States: Study Results from NHANES (1999–2016)
Qiyuan Bai, Hao Chen, Zhen Gao, Xuhua Li, Jiapeng Li, Shidong Liu, Bing Song, Cuntao Yu
Reviews in Cardiovascular Medicine.2025;[Epub] CrossRef
Association between underweight and risk of heart failure in diabetes patients
Tae Kyung Yoo, Kyung‐Do Han, Eun‐Jung Rhee, Won‐Young Lee
Journal of Cachexia, Sarcopenia and Muscle.2024; 15(2): 671. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Research on obesity using the National Health Information Database: recent trends
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 35. CrossRef
Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovascular Diabetology.2023;[Epub] CrossRef
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 & Metabolism Journal.2023; 47(6): 846. CrossRef
Characterization of the oxidative stress and inflammatory markers in metabolically healthy obese individuals
Hazhmat Ali
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The Influence of Obesity and Metabolic Health on Vascular Health
Eun-Jung Rhee
Endocrinology and Metabolism.2022; 37(1): 1. CrossRef
Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients
Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2022; 46(2): 327. CrossRef
Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
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Seon-Ah Cha, Jae-Seung Yun, Gee-Hee Kim, Yu-Bae Ahn
Cardiovascular Diabetology.2022;[Epub] CrossRef
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O. V. Tsygankova, N. E. Evdokimova, V. V. Veretyuk, L. D. Latyntseva, A. S. Ametov
Diabetes mellitus.2022; 25(6): 535. CrossRef
The association between metabolic syndrome and heart failure in middle-aged male and female: Korean population-based study of 2 million individuals
Tae-Eun Kim, Hyeongsu Kim, JiDong Sung, Duk-Kyung Kim, Myoung-Soon Lee, Seong Woo Han, Hyun-Joong Kim, Sung Hea Kim, Kyu-Hyung Ryu
Epidemiology and Health.2022; 44: e2022078. CrossRef
Diabetes and Heart Failure
Eun-Jung Rhee
The Journal of Korean Diabetes.2021; 22(1): 12. CrossRef
Prediabetes and the risk of heart failure: A meta‐analysis
Xiaoyan Cai, Xiong Liu, Lichang Sun, Yiting He, Sulin Zheng, Yang Zhang, Yuli Huang
Diabetes, Obesity and Metabolism.2021; 23(8): 1746. CrossRef
Diabetes and Heart Failure
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2021; 3(2): 21. CrossRef
Effects of Lipid Overload on Heart in Metabolic Diseases
An Yan, Guinan Xie, Xinya Ding, Yi Wang, Liping Guo
Hormone and Metabolic Research.2021; 53(12): 771. CrossRef
Obesity Degree and Glycemic Status: Factors That Should Be Considered in Heart Failure
Hye Soon Kim
Diabetes & Metabolism Journal.2020; 44(4): 529. CrossRef
Letter: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Darae Kim
Diabetes & Metabolism Journal.2020; 44(5): 777. CrossRef
Response: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2020; 44(5): 781. CrossRef

Metabolic Risk/Epidemiology
Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women: Seung Eun Lee, Ji Yeon Baek, Kyungdo Han, Eun Hee Koh; Diabetes Metab J. 2021;45(2):175-182. Published online April 14, 2020; DOI: https://doi.org/10.4093/dmj.2019.0150

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146 Download
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Graphical Abstract Abstract PDF PubReader ePub

Background

Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.

Methods

A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.

Results

In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.

Conclusion

Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Citations

Citations to this article as recorded by

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Association between thyroid hormone resistance and obesity: a cross‐sectional study and mouse stimulation test
Zhihui Wang, Huimin Yu, Kai Wang, Junming Han, Yongfeng Song
Obesity.2024; 32(8): 1483. CrossRef

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