Diabetes & Metabolism Journal

Original Articles

Complications
Time-Window Stratified Machine-Learning Risk Prediction Model for Diabetic Retinopathy and Cross-Cohort Study: Jingwen Hui, Zheya Han, Yuxi Bai, Yawen Gong, Quanhong Han, Xuehao Cui; Received November 1, 2025 Accepted December 18, 2025 Published online April 15, 2026; DOI: https://doi.org/10.4093/dmj.2025.1098 [Epub ahead of print]

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Abstract PDF: Background
Diabetic retinopathy (DR) remains a significant cause of vision loss worldwide. Existing risk models rarely account for when DR develops relative to the onset of diabetes, even though early- and late-onset disease may have different clinical implications. We hypothesized that DR occurring within 6 years of diabetes diagnosis (short-term) represents an early-onset phenotype driven mainly by metabolic dysregulation and microvascular injury, whereas DR developing after 6 years (long-term) reflects late-onset disease shaped by cumulative metabolic burden and aging. This study aimed to develop and validate a time-window- stratified DR risk prediction model.
Methods
Data from two large cohorts (UK Biobank and Tianjin Eye Hospital) were analyzed, including 1,943 patients with diabetes but without DR at baseline. Separate Cox models were built for short-term (≤6 years) and long-term (>6 years) DR incidence. Feature selection used least absolute shrinkage and selection operator (LASSO) and Boruta algorithms, and model performance was assessed by area under the curve (AUC), calibration, and decision curve analyses. Machine-learning models were further developed on pooled data for multiclass classification (no DR, short-term DR, long-term DR) and interpretability using SHapley Additive exPlanations (SHAP) analysis.
Results
Both models identified glycosylated hemoglobin and retinal neurostructural measures (retinal nerve fiber layer thickness and retinal ganglion cell layer thickness) as consistent predictors, indicating that neuroretinal degeneration precedes clinical DR. The short-term model emphasized renal and lipid metabolism markers, whereas the long-term model highlighted age and uric acid. Internal validation and cross-cohort replication showed stable discrimination (AUC 0.79–0.84). The pooled XGBoost model improved accuracy (overall approximately 80%) with transparent interpretability.
Conclusion
Time-window-based modeling revealed distinct early- and late-onset DR risk profiles, thereby enhancing prediction precision. Integrating optical coherence tomography imaging with routine clinical variables offers a practical, interpretable framework for individualized risk assessment and early intervention in DR.

Lifestyle and Behavioral Interventions
Influence of Fibroblast Growth Factor 21 on Delayed Glycemic Improvement Following Acute Exercise in Type 2 Diabetes Mellitus: Ying Zhang, Dan Liu, Yurun Lu, Piao Kang, Xinyu Liu, Qinyi Wang, Anran Chen, Di Cheng, Liang Wu, Qi Li, Xiaolin Wang, Yanli Li, Yaorui Ye, Jingyi Yang, Jiacheng Ni, Qichen Fang, Zhe Huang, Aimin Xu, Weiping Jia, Yong Wang, Guowang Xu, Huating Li; Received December 12, 2024 Accepted October 14, 2025 Published online March 25, 2026; DOI: https://doi.org/10.4093/dmj.2024.0814 [Epub ahead of print]

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Exercise positively influences glycemic control. Some individuals experience greater glycemic stability on the day after exercise, even without additional physical activity. However, the mechanisms underlying this delayed glycemic improvement remain unclear.
Methods
Seventy-one patients with type 2 diabetes mellitus were assigned to either a 60-minute exercise or resting group. Serum fibroblast growth factor 21 (FGF21) levels and untargeted metabolomic profiling were assessed at multiple time points before and after exercise. Interstitial glucose levels were monitored using continuous glucose monitoring system. FGF21 knockout mice and wildtype littermates on a high-fat diet, underwent a 3-week exercise intervention, and supplemented with recombinant mouse FGF21.
Results
Individuals exhibiting delayed glycemic improvement (responders) displayed a significantly stronger FGF21 response compared to non-responders. Baseline metabolites, including p-cresol sulfate and dimethylglycine, differed between responders and non-responders and were associated with the FGF21 response. Longitudinal time-series analyses revealed post-exercise differences in acylcarnitines, fatty acids, and complex lipids between responders and non-responders. Dynamic correlation and mediation analyses supported that FGF21 modulates delayed glycemic improvement via regulation of lipid metabolism. In vivo FGF21 knockout and rescue experiments demonstrated that FGF21 is necessary for these metabolic shifts and for the associated improvements in glucose tolerance and insulin sensitivity.
Conclusion
This study finds that the baseline metabolome is associated with the magnitude of the post-exercise FGF21 response, which influences delayed glycemic improvements through regulation of lipid metabolism pathways.

Lifestyle and Behavioral Interventions
Association between Changes in Physical Activity and Incident Depression among Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Sangwoo Park, Back Kim, Hye Jun Kim, Sun Jae Park, Jihun Song, Jina Chung, Seogsong Jeong, Sang Min Park, Dae Ho Lee, Soo Jung Choi; Received August 17, 2025 Accepted December 18, 2025 Published online February 23, 2026; DOI: https://doi.org/10.4093/dmj.2025.0766 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study aims to investigate the relationship between changes in physical activity patterns following a new diagnosis of type 2 diabetes mellitus (T2DM) and the risk of developing depression.
Methods
This study utilized comprehensive diabetes data from the National Health Insurance Service of South Korea. From this dataset, we included 254,619 individuals newly diagnosed with T2DM between 2009 and 2015 who had health examination data within 2 years before and after their diagnosis date and no prior history of depression. Physical activity levels were quantified using the metabolic equivalent of task (MET) method.
Results
Compared to individuals with 0 MET-min/wk of physical activity prior to a new T2DM diagnosis, those who increased their activity levels to 500–999 MET-min/wk after diagnosis showed a 23% reduction in the risk of depression, while an increase to ≥1,000 MET-min/wk was associated with a 25% reduction in depression risk. Conversely, individuals with 1–499 MET-min/wk before diagnosis who became inactive after diagnosis experienced a 25% increased risk of depression. A similar trend of increased depression risk was observed in those who reduced their physical activity from 500–999 or ≥1,000 MET-min/wk.
Conclusion
Changes in physical activity levels before and after a new diagnosis of T2DM significantly influence the risk of developing depression, with increased activity reducing the risk and decreased activity elevating the risk. This finding underscores the importance of encouraging physical activity to support mental health in patients with newly diagnosed T2DM.

Cardiovascular Risk/Epidemiology
Prognostic Impact of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Coronary Ischemia: A Retrospective Cohort Study: Haochen Xuan, Yik-Ming Hung, Ran Guo, Qingwen Ren, Jiayi Huang, Jingnan Zhang, Wenli Gu, Ho-Leung Chan, Gaozhen Cao, Run Wang, Calvin Ka-Lam Leung, Tongda Xu, Kai-Hang Yiu; Received March 11, 2025 Accepted July 22, 2025 Published online October 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0200 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Patients with type 2 diabetes mellitus (T2DM) and coronary ischemia face an exceptionally elevated risk, and the achievement of complete revascularization (CR) within this population could be challenging.
Methods
Patients with T2DM and coronary ischemia based on coronary angiography and retrospective angiographic fractional flow reserve analysis between 2014 and 2016 were included. The impact of the extent of revascularization on the improvement of endpoint events by sodium-glucose cotransporter 2 (SGLT2) inhibitors was analyzed. The primary study endpoint was major adverse cardiac events (MACE), while all-cause mortality served as secondary endpoints. Kaplan-Meier analysis and Cox proportional hazards regression model were adopted to assess the association between SGLT2 inhibitors and endpoint incidence.
Results
A total of 671 patients were identified. Among them, 206 (30.7%) were prescribed with SGLT2 inhibitors, while 484 (72.1%) achieved CR after the operation. During a mean 36-month follow-up, 100 MACE and 89 all-cause mortality were recorded. SGLT2 inhibitor users demonstrated lower rates of MACE (8.3% vs. 17.8%, P=0.002) and all-cause mortality (6.3% vs. 16.3%, P<0.001) compared to non-users. After adjusting for confounding factors in multivariable Cox analysis, the association between SGLT2 inhibitors and reduced MACE incidence remained consistent both in the CR and incomplete revascularization subgroups (hazard ratio [HR], 0.498; 95% confidence interval [CI], 0.246 to 0.938; P=0.040; and HR, 0.341; 95% CI, 0.123 to 0.805; P=0.023, respectively).
Conclusion
SGLT2 inhibitors were found to be associated with a reduced risk of 3-year MACE and all-cause mortality in patients with T2DM and coronary ischemia, regardless of extent of revascularization.

Complications
Targeting SLC25A33 Suppresses Vascular Smooth Muscle Cell Proliferation and Migration by Reducing Cytosolic mtDNA Levels: Implications for Occlusive Vascular Diseases: Daehoon Kim, Jieun Shin, Yeon-Kyung Choi, You Mie Lee, Keun-Gyu Park, Hyang Sook Kim, Jun-Kyu Byun; Diabetes Metab J. 2026;50(1):139-152. Published online July 30, 2025; DOI: https://doi.org/10.4093/dmj.2024.0632

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Abstract PDF Supplementary Material PubReader ePub: Background
Vascular smooth muscle cells (VSMCs) play a crucial role in the development of occlusive vascular diseases through abnormal proliferation and migration. This pathological behavior is closely associated with mitochondrial reactive oxygen species (ROS)-mediated mitochondrial DNA (mtDNA) damage. The mitochondrial carrier protein solute carrier family 25 member 33 (SLC25A33), essential for nucleoside transport, is integral to mtDNA production. This study aimed to investigate the effects of SLC25A33 inhibition on the proliferation and migration of VSMCs, as well as its impact on neointima formation.
Methods
VSMCs were isolated from the thoracic aorta of 4-week-old Sprague-Dawley rats. The effects of small interfering RNAinduced silencing of SLC25A33 mRNA on platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs were analyzed. The in vivo effects of targeting the SLC25A33 gene on neointima formation were evaluated using a murine carotid artery ligation model by perivascularly applying Lenti-shSLC25A33 with Pluronic F-127 gel.
Results
First, we observed an upregulation of the SLC25A33 protein in the carotid artery ligation-induced neointima in mice. Silencing of SLC25A33 suppressed the PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Knockdown of SLC25A33 inhibited PDGF-induced production of mtDNA and ROS, consequently inactivating the cyclic GMP-AMP synthesis (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1)-nuclear factor kappa B (NF-κB) pathway. Furthermore, the downregulation of SLC25A33 reduced carotid artery ligation-induced neointima in mice.
Conclusion
This study suggests that targeting SLC25A33 in VSMCs could be a novel therapeutic strategy to prevent occlusive vascular diseases.

Review

Basic and Translational Research
Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases: Yeon Jin Roh, Hyeonki Kim, Dong Wook Choi; Diabetes Metab J. 2025;49(3):368-385. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0195

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The liver plays a fundamental role in metabolic homeostasis, integrating systemic fuel utilization with the progression of various metabolic diseases. Hepatic stellate cells (HSCs) are a key nonparenchymal cell type in the liver, which is essential for maintaining hepatic architecture in their quiescent state. However, upon chronic liver injury or metabolic stress, HSCs become activated, leading to excessive extracellular matrix deposition and pro-fibrotic signaling, ultimately positioning them as key players in liver pathology. Emerging evidence highlights the critical roles of metabolic reprogramming and epigenetic regulation in HSCs activation. HSCs activation is driven by both intrinsic fuel metabolism reprogramming and extrinsic metabolic cues from the microenvironment, while the metabolic intermediates actively reshape the epigenetic landscape, reinforcing fibrogenic transcriptional programs. In this review, we summarize recent advances in understanding how metabolic and epigenetic alterations drive HSCs activation, thereby shaping transcriptional programs that sustain fibrosis, and discuss potential therapeutic strategies to target these interconnected pathways in human metabolic diseases.

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Original Articles

Others
Fibroblast Growth Factor 21 Levels Are Associated With Perception and Neural Responses to Sweetness in Type 2 Diabetes Mellitus: Piao Kang, Ying Zhang, Dian Zeng, Dan Liu, Rui Han, Yuwei Lu, Di Cheng, Qinyi Wang, Silin Liu, Liang Wu, Qian Wu, Shujie Yu, Anran Chen, Jingyi Guo, Wenli Ge, Jiacheng Ni, Jingyi Yang, Xiaomeng Wu, Lifei Ma, Weiping Jia, Qichen Fang, Yuehua Li, Huating Li; Diabetes Metab J. 2025;49(4):893-905. Published online March 26, 2025; DOI: https://doi.org/10.4093/dmj.2024.0390

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Background
The relationship between fibroblast growth factor 21 (FGF21) and sweet taste perception and preference in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to investigate this relationship and examine the neural responses of T2DM patients to high-calorie sweet (HCS) food pictures, further exploring its correlation with FGF21 levels.
Methods
We assessed sweet taste perception and preference in 40 T2DM patients and 41 controls using classical scales. Subsequently, the neural responses of 11 T2DM patients and 11 controls to HCS pictures were examined using functional magnetic resonance imaging. FGF21 levels were measured using chemiluminescent immunoassay, and the correlations with taste perception and neural responses were analyzed.
Results
Increased FGF21 levels were associated with decreased sweet perception and increased sweet taste preference in T2DM patients. Compared to control, T2DM patients exhibited greater neural activations in the orbitofrontal cortex, anterior cingulate cortex (ACC), thalamus, and hippocampus (HCS vs. non-food) as well as the putamen (HCS vs. low-calorie food). Notable differences were observed in the parahippocampal gyrus, insula, ACC, and hippocampus in T2DM patients (HCS vs. high-calorie non-sweet). Additionally, FGF21 accounted for 30.39% and 32.4% of the associations between T2DM and ACC, and parahippocampal gyrus, respectively.
Conclusion
FGF21 levels were independently associated with changes in sweet taste perception and preference in T2DM patients and were significantly associated with activation in reward-related brain regions. This study reveals the potential role of FGF21 in regulating responses to sweet foods in T2DM and provides insight to develop new therapeutic strategies for diabetes.

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Exploring Biomarkers in Type 2 Diabetes Mellitus versus Normoglycemia Identified through High-Throughput Proteomics: A Systematic Review and Meta-Analysis
Julia García-Currás, Raquel Pérez-Lois, Guillermo L. Taboada, María P. Pata
Journal of Proteome Research.2026; 25(1): 4. CrossRef
Efimosfermin for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH): Mechanism of Action, Clinical Development and Emerging Therapeutic Potential
Mariam Alamgir, Aalam Sohal, Kris Kowdley
Drug Design, Development and Therapy.2026; Volume 20: 1. CrossRef

Complications
Global, Regional, and National Temporal Trends in Incidence for Type 2 Diabetes Mellitus Related Chronic Kidney Disease from 1992 to 2021: Yu Cao, Huiting Chen, Hui Liu, Hao Wu, Wei Gao; Diabetes Metab J. 2025;49(4):848-861. Published online March 11, 2025; DOI: https://doi.org/10.4093/dmj.2024.0593

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Background
Type 2 diabetes mellitus (T2DM) is a major cause of declining renal function.
Methods
Temporal trends in T2DM-related chronic kidney disease (CKD-T2DM) incidence across 204 countries and territories from 1992 to 2021 were analyzed using data from the Global Burden of Disease 2021. The impact of macro-factors (demographic change, age, period, and birth cohort) on CKD-T2DM incidence trends was assessed using decomposition analyses and age-period- cohort modeling, highlighting opportunities to improve incidence and reduce regional disparities.
Results
In 2021, global CKD-T2DM incidence cases reached 2.01 million, a 150.92% increase since 1992, with population growth and aging contributing to 80% of this rise. The age-standardized incidence rate (ASIR) ranged from 15.09 per 100,000 in low sociodemographic index (SDI) regions to 23.07 in high SDI regions. China, India, the United States, and Japan have the most incidence cases, accounted for 69% of incidence cases globally. With 175 countries showing an increasing ASIR trend. Unfavorable trend in ASIR increase were generally found in most high-middle and middle SDI countries, such as China and Mexico (net drift=0.15% and 1.17%, per year). Age-period-cohort analyses indicated a high incidence risk near age 80, with worsening risks for recent periods and birth cohorts, except in high SDI areas.
Conclusion
The CKD-T2DM incidence burden continues to rise globally, with significant variations between countries, posing major global health implications. CKD-T2DM is largely preventable and treatable, warranting greater attention in global health policy, particularly for older populations and in low and middle SDI regions.

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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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The immunometabolic network in obesity-associated insulin resistance: a systemic multi-organ and multi-cellular perspective
Yi Zhang, Haixin Ding, Xue Zhao, Yutong Li, Pengling Ge
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Metabolic Risk/Epidemiology
An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data: Chang-Myung Oh, Ji-In Bang, Sang Yoon Lee, Jae Kyung Lee, Jee Won Chai, So Won Oh; Diabetes Metab J. 2025;49(1):92-104. Published online September 2, 2024; DOI: https://doi.org/10.4093/dmj.2024.0057

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Background
F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging.
Methods
We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022.
Results
In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only.
Conclusion
FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.

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Complications
Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy: Kangmin Lee, Ga Hye Lee, Seung Eun Lee, Jee Myung Yang, Kunho Bae; Diabetes Metab J. 2024;48(5):983-992. Published online March 13, 2024; DOI: https://doi.org/10.4093/dmj.2023.0149

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Background
To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR).
Methods
This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls.
Results
In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups.
Conclusion
OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

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Ligang Jiang, Yimei Ji, Xin Jiang, Yune Zhao
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Flow and ischemic changes in retina and choroid across diabetic retinopathy spectrum: a SS-OCTA study
Qianhui Yang, Kelvin Y. C. Teo, Yueheng Hong, Bingyao Tan, Leopold Schmetterer, Chui Ming Gemmy Cheung, Tien Yin Wong, Gavin Tan Siew Wei
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Lifestyle
Associations of Ultra-Processed Food Intake with Body Fat and Skeletal Muscle Mass by Sociodemographic Factors: Sukyoung Jung, Jaehee Seo, Jee Young Kim, Sohyun Park; Diabetes Metab J. 2024;48(4):780-789. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0335

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Background
The effects of excessive ultra-processed food (UPF) consumption on body composition measures or sociodemographic disparities are understudied in Korea. We aimed to investigate the association of UPF intake with percent body fat (PBF) and percent appendicular skeletal muscle mass (PASM) by sociodemographic status in adults.
Methods
This study used data from the Korea National Health and Nutrition Examination Survey 2008–2011 (n=11,123 aged ≥40 years). We used a NOVA system to classify all foods reported in a 24-hour dietary recall, and the percentage of energy intake (%kcal) from UPFs was estimated. PBF and PASM were measured by dual-energy X-ray absorptiometry. Tertile (T) 3 of PBF indicated adiposity and T1 of PASM indicated low skeletal muscle mass, respectively. Multinomial logistic regression models were used to estimate odds ratios (OR) with 95% confidence interval (CI) after adjusting covariates.
Results
UPF intake was positively associated with PBF-defined adiposity (OR_{per 10% increase}, 1.04; 95% CI, 1.002 to 1.08) and low PASM (OR_{per 10% increase}, 1.05; 95% CI, 1.01 to 1.09). These associations were stronger in rural residents (PBF: OR_{per 10% increase}, 1.14; 95% CI, 1.06 to 1.23; PASM: OR_{per 10% increase}, 1.15; 95% CI, 1.07 to 1.23) and not college graduates (PBF: OR_{per 10% increase}, 1.06; 95% CI, 1.02 to 1.11; PASM: OR_{per 10% increase}, 1.07; 95% CI, 1.03 to 1.12) than their counterparts.
Conclusion
A higher UPF intake was associated with higher adiposity and lower skeletal muscle mass among Korean adults aged 40 years and older, particularly in those from rural areas and with lower education levels.

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Review

Basic Research
Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases: Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong; Diabetes Metab J. 2024;48(1):1-18. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2023.0115

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Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPR^mt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPR^mt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.

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Original Articles

Basic Research
DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis: Dong-Keon Lee, Su Ho Jo, Eun Soo Lee, Kyung Bong Ha, Na Won Park, Deok-Hoon Kong, Sang-In Park, Joon Seok Park, Choon Hee Chung; Diabetes Metab J. 2024;48(1):97-111. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0367

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Background
Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression.
Methods
Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture.
Results
DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis.
Conclusion
Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

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Basic Research
Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2024;48(1):83-96. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0363

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Background
Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system.
Methods
To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide.
Results
Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs.
Conclusion
These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.

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Basic Research
Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor β/Smad3 Signaling Pathway: Kyeong-Min Lee, Yeo Jin Hwang, Gwon-Soo Jung; Diabetes Metab J. 2024;48(1):72-82. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0231

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Background
Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells.
Methods
To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-β-treated renal cells in vitro.
Results
Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-βstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-β-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-β secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines.
Conclusion
Alantolactone improves renal fibrosis by inhibiting the TGF-β/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.

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Review

Cardiovascular Risk/Epidemiology
The Role of Echocardiography in Evaluating Cardiovascular Diseases in Patients with Diabetes Mellitus: Sun Hwa Lee, Jae-Hyeong Park; Diabetes Metab J. 2023;47(4):470-483. Published online July 27, 2023; DOI: https://doi.org/10.4093/dmj.2023.0036

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Patients with diabetes mellitus are highly susceptible to cardiovascular complications, which are directly correlated with cardiovascular morbidity and mortality. In addition to coronary artery disease, there is growing awareness of the risk and prevalence of heart failure (HF) in patients with diabetes. Echocardiography is an essential diagnostic modality commonly performed in patients with symptoms suggestive of cardiovascular diseases (CVD), such as dyspnea or chest pain, to establish or rule out the cause of symptoms. Conventional echocardiographic parameters, such as left ventricular ejection fraction, are helpful not only for diagnosing CVD but also for determining severity, treatment strategy, prognosis, and response to treatment. Echocardiographic myocardial strain, a novel echocardiographic technique, enables the detection of early changes in ventricular dysfunction before HF symptoms develop. This article aims to review the role of echocardiography in evaluating CVD in patients with diabetes mellitus and how to use it in patients with suspected cardiac diseases.

Citations

Citations to this article as recorded by

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Valores Ecocardiográficos de Referência para as Câmaras Cardíacas no Brasil: Um Estudo Multirregional e Multirracial
Ana Clara Tude Rodrigues, Roberto Magalhães Saraiva, Viviane T. Hotta, Gabriel Doreto Rodrigues, Fabiana Camelier de Assis Cardoso, Anderson da Costa Armstrong, Cláudia Gianini Monaco, Adelino Parro Junior, José Luis de Castro e Silva Pretto, João Marcos
Arquivos Brasileiros de Cardiologia.2026;[Epub] CrossRef
Role of Echocardiography in Detecting Left Ventricular Dysfunction Among Diabetic Patients: A Clinical and Biochemical Perspective
Chandu Siripuram, K. Balu Mahendran, Shreelaxmi V Hegde, Sanjana Murali Krishna, Shruti Suresh Suvarna, Ramesh Kandimalla
Cureus.2025;[Epub] CrossRef
Progression of cardiac dysfunction in patients with type 2 diabetes without overt cardiovascular disease: A three‐year follow‐up echocardiographic study (DIACAR)
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Original Article

Basic Research
Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis: Kyung Bong Ha, Eun Soo Lee, Na Won Park, Su Ho Jo, Soyeon Shim, Dae-Kee Kim, Chan Mug Ahn, Choon Hee Chung; Diabetes Metab J. 2023;47(4):500-513. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0110

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Background
Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.
Methods
Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.
Results
TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Conclusion
Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

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Reviews

Others
Current Trends of Big Data Research Using the Korean National Health Information Database: Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee; Diabetes Metab J. 2022;46(4):552-563. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0193

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Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

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Islet Studies and Transplantation
Regulation of Pancreatic β-Cell Mass by Gene-Environment Interaction: Shun-ichiro Asahara, Hiroyuki Inoue, Yoshiaki Kido; Diabetes Metab J. 2022;46(1):38-48. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0045

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The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on “gene-environment interactions” in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.

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Original Articles

Metabolic Risk/Epidemiology
Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus: Eun Hee Kim, Hong-Kyu Kim, Min Jung Lee, Sung-Jin Bae, Jaewon Choe, Chang Hee Jung, Chul-Hee Kim, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(3):486-498. Published online November 18, 2021; DOI: https://doi.org/10.4093/dmj.2021.0095

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Background
This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM).
Methods
A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline.
Results
During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm² and 1.08 in men, respectively, and 85.7 cm² and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively.
Conclusion
Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm² or VSR ≥1.0 in men; VFA ≥85 cm² or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

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Complications
SUDOSCAN in Combination with the Michigan Neuropathy Screening Instrument Is an Effective Tool for Screening Diabetic Peripheral Neuropathy: Tae Jung Oh, Yoojung Song, Hak Chul Jang, Sung Hee Choi; Diabetes Metab J. 2022;46(2):319-326. Published online September 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0014

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Background
Screening for diabetic peripheral neuropathy (DPN) is important to prevent severe foot complication, but the detection rate of DPN is unsatisfactory. We investigated whether SUDOSCAN combined with Michigan Neuropathy Screening Instrument (MNSI) could be an effective tool for screening for DPN in people with type 2 diabetes mellitus (T2DM) in clinical practice.
Methods
We analysed the data for 144 people with T2DM without other cause of neuropathy. The presence of DPN was confirmed according to the Toronto Consensus criteria. Electrochemical skin conductance (ESC) of the feet was assessed using SUDOSCAN. We compared the discrimination power of following methods, MNSI only vs. SUDOSCAN only vs. MNSI plus SUDOSCAN vs. MNSI plus 10-g monofilament test.
Results
Confirmed DPN was detected in 27.8% of the participants. The optimal cut-off value of feet ESC to distinguish DPN was 56 μS. We made the DPN screening scores using the corresponding odds ratios for MNSI-Questionnaire, MNSI-Physical Examination, SUDOSCAN, and 10-g monofilament test. For distinguishing the presence of DPN, the MNSI plus SUDOSCAN model showed higher areas under the receiver operating characteristic curve (AUC) than MNSI only model (0.717 vs. 0.638, P=0.011), and SUDOSCAN only model or MNSI plus 10-g monofilament test showed comparable AUC with MNSI only model.
Conclusion
The screening model for DPN that includes both MNSI and SUDOSCAN can detect DPN with acceptable discrimination power and it may be useful in Korean patients with T2DM.

Citations

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Sijia Fei, Jingwen Fan, Jiaming Cao, Huan Chen, Xiaoxia Wang, Qi Pan
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Okti Sri Purwanti, Nursalam Nursalam, Moses Glorino Rumambo Pandin
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María Mogilevskaya, Mariana Gaviria-Carrillo, John Edwin Feliciano-Alfonso, Ana M. Barragan, Carlos A. Calderon-Ospina, Mauricio O. Nava-Mesa, Syed Anees Ahmed
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Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
The value of electrochemical skin conductance measurement by Sudoscan® for assessing autonomic dysfunction in peripheral neuropathies beyond diabetes
Jean-Pascal Lefaucheur
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Autonomic Nerve Function Tests in Patients with Diabetes
Heung Yong Jin, Tae Sun Park
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Electrochemical Skin Conductance by Sudoscan in Non-Dialysis Chronic Kidney Disease Patients
Liang-Te Chiu, Yu-Li Lin, Chih-Hsien Wang, Chii-Min Hwu, Hung-Hsiang Liou, Bang-Gee Hsu
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The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes
Tae Jung Oh, Han Song, Youngil Koh, Sung Hee Choi
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Case report: Significant relief of linezolid-induced peripheral neuropathy in a pre-XDR-TB case after acupuncture treatment
Yuping Mo, Zhu Zhu, Jie Tan, Zhilin Liang, Jiahui Wu, Xingcheng Chen, Ming Hu, Peize Zhang, Guofang Deng, Liang Fu
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Detection of sudomotor alterations evaluated by Sudoscan in patients with recently diagnosed type 2 diabetes
Ana Cristina García-Ulloa, Paloma Almeda-Valdes, Teresa Enedina Cuatecontzi-Xochitiotzi, Jorge Alberto Ramírez-García, Michelle Díaz-Pineda, Fernanda Garnica-Carrillo, Alejandra González-Duarte, K M Venkat Narayan, Carlos Alberto Aguilar-Salinas, Sergio H
BMJ Open Diabetes Research & Care.2022; 10(6): e003005. CrossRef

Complications
Screening Tools Based on Nomogram for Diabetic Kidney Diseases in Chinese Type 2 Diabetes Mellitus Patients: Ganyi Wang, Biyao Wang, Gaoxing Qiao, Hao Lou, Fei Xu, Zhan Chen, Shiwei Chen; Diabetes Metab J. 2021;45(5):708-718. Published online April 13, 2021; DOI: https://doi.org/10.4093/dmj.2020.0117

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Background
The influencing factors of diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM) were explored to develop and validate a DKD diagnostic tool based on nomogram approach for patients with T2DM.
Methods
A total of 2,163 in-hospital patients with diabetes diagnosed from March 2015 to March 2017 were enrolled. Specified logistic regression models were used to screen the factors and establish four different diagnostic tools based on nomogram according to the final included variables. Discrimination and calibration were used to assess the performance of screening tools.
Results
Among the 2,163 participants with diabetes (1,227 men and 949 women), 313 patients (194 men and 120 women) were diagnosed with DKD. Four different screening equations (full model, laboratory-based model 1 [LBM1], laboratory-based model 2 [LBM2], and simplified model) showed good discriminations and calibrations. The C-indexes were 0.8450 (95% confidence interval [CI], 0.8202 to 0.8690) for full model, 0.8149 (95% CI, 0.7892 to 0.8405) for LBM1, 0.8171 (95% CI, 0.7912 to 0.8430) for LBM2, and 0.8083 (95% CI, 0.7824 to 0.8342) for simplified model. According to Hosmer-Lemeshow goodness-of-fit test, good agreement between the predicted and observed DKD events in patients with diabetes was observed for full model (χ²=3.2756, P=0.9159), LBM1 (χ²=7.749, P=0.4584), LBM2 (χ²=10.023, P=0.2634), and simplified model (χ²=12.294, P=0.1387).
Conclusion
LBM1, LBM2, and simplified model exhibited excellent predictive performance and availability and could be recommended for screening DKD cases among Chinese patients with diabetes.

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Multi-feature integrated machine learning prediction model for early nephropathy in elderly living with type 2 diabetes mellitus
Tingting Fang, Yuanyuan Yang, Feng Zhuo, Xinran Xie, Jialun Song, Linghua Kong
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Machine learning-based risk predictive models for diabetic kidney disease in type 2 diabetes mellitus patients: a systematic review and meta-analysis
Yihan Li, Nan Jin, Qiuzhong Zhan, Yue Huang, Aochuan Sun, Fen Yin, Zhuangzhuang Li, Jiayu Hu, Zhengtang Liu
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Deep learning for early detection of chronic kidney disease stages in diabetes patients: A TabNet approach
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Predictive model combining blood pressure, glycemic and renal markers for diabetic nephropathy in elderly hypertensive patients with type 2 diabetes
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Changes in urinary exosomal protein CALM1 may serve as an early noninvasive biomarker for diagnosing diabetic kidney disease
Tao Li, Tian ci Liu, Na Liu, Man Zhang
Clinica Chimica Acta.2023; 547: 117466. CrossRef
Development and validation of a novel nomogram to predict diabetic kidney disease in patients with type 2 diabetic mellitus and proteinuric kidney disease
Hui Zhuan Tan, Jason Chon Jun Choo, Stephanie Fook-Chong, Yok Mooi Chin, Choong Meng Chan, Chieh Suai Tan, Keng Thye Woo, Jia Liang Kwek
International Urology and Nephrology.2022; 55(1): 191. CrossRef
Nomogram-Based Chronic Kidney Disease Prediction Model for Type 1 Diabetes Mellitus Patients Using Routine Pathological Data
Nakib Hayat Chowdhury, Mamun Bin Ibne Reaz, Sawal Hamid Md Ali, Shamim Ahmad, María Liz Crespo, Andrés Cicuttin, Fahmida Haque, Ahmad Ashrif A. Bakar, Mohammad Arif Sobhan Bhuiyan
Journal of Personalized Medicine.2022; 12(9): 1507. CrossRef
Development and assessment of diabetic nephropathy prediction model using hub genes identified by weighted correlation network analysis
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Aging.2022; 14(19): 8095. CrossRef

Basic Research
Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy: Guang-Yin Shen, Jeong-Hun Shin, Yi-Sun Song, Hyun-Woo Joo, In-Hwa Park, Jin-Hee Seong, Na-Kyoung Shin, A-Hyeon Lee, Young Jong Cho, Yonggu Lee, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim; Diabetes Metab J. 2021;45(4):594-605. Published online February 26, 2021; DOI: https://doi.org/10.4093/dmj.2020.0049

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Background
We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy.
Methods
Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit.
Results
G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro.
Conclusion
Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

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Brief Report

Complications
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015): Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park; Diabetes Metab J. 2021;45(1):115-119. Published online December 18, 2020; DOI: https://doi.org/10.4093/dmj.2020.0120

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This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

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How does diabetic peripheral neuropathy impact patients' burden of illness and the economy? A retrospective study in Beijing, China
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Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
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Diabetes & Metabolism Journal.2021; 45(3): 459. CrossRef
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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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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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The Close Link Between Obesity and Cardiovascular Disease
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Gobardhan Kathariya, Jyoti Aggarwal, Rajesh Nandal, Mayank Madan, Sreenivas Reddy
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Technology/Device
Data Configuration and Publication Trends for the Korean National Health Insurance and Health Insurance Review & Assessment Database: Hae Kyung Kim, Sun Ok Song, Junghyun Noh, In-Kyung Jeong, Byung-Wan Lee; Diabetes Metab J. 2020;44(5):671-678. Published online October 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0207

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Background
Big data reports related to diseases and health care for the Korean population have been published since the National Health Insurance Service (NHIS) and the Health Insurance Review & Assessment (HIRA) Service provided limited open access to their databases. Here, we reviewed the structure, content, and means of using data from the National Health Insurance (NHI) system for the benefit of Korean researchers and presented the latest publication trends in Korean healthcare data procured from the NHI and HIRA databases.
Methods
Since 2013, researchers have been able to obtain nationwide population-based studies using the NHI and HIRA databases of the insured. We searched publications using the NHI and the HIRA databases between 2013 and 2019 retrieved from PubMed.
Results
The NHI and HIRA databases provide nationwide population-based data. The total number of publications from 2014 to 2019 using NHI and HIRA databases is 2,541 and 655, respectively. A total of 5,465 endocrinology-related studies were performed during 2014 to 2019.
Conclusion
The NHIS and HIRA databases have provided tools for guidelines to approach world-leading population-based epidemiology and disease research.

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European Journal of Heart Failure.2026;[Epub] CrossRef
Long-term exposure to fine particle air pollution associated with emergency COVID-19 hospitalizations: A nationwide retrospective Korean cohort study
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Public Health.2026; 253: 106189. CrossRef
Psychiatric, Cardiovascular and Skeletal Risks of Codeine versus Oxycodone in Hip Osteoarthritis: A Population-Based Cohort Study
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Drug Design, Development and Therapy.2026; Volume 20: 1. CrossRef
Longitudinal changes in cardiorespiratory fitness and risk of depressive and anxiety disorders in a nationwide cohort of 7 million participants
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Scientific Reports.2026;[Epub] CrossRef
Estimation of healthy worker survivor bias among middle-aged populations in Korea
Byungyoon Yun, Beom Kyung Kim, Sung-In Jang, Laura S Rozek, Heejin Kimm, Juyeon Oh, Jin-Ha Yoon
International Journal of Epidemiology.2026;[Epub] CrossRef
Risk of Liver and Kidney Adverse Events After Androgen Deprivation Therapy in Prostate Cancer: A Population-Based Retrospective Cohort Study
Jiwoo Yun, Ah-Young Kim, Il-Hyung Hwang, Sukhyang Lee, Hankil Lee
Journal of Urologic Oncology.2026; 24(1): 21. CrossRef
Incidence of systemic vasculitides after Mycobacterium tuberculosis infection: a population-based cohort study in Korea
Minkyung Han, Jang Woo Ha, Inkyung Jung, Chi Young Kim, Sung Soo Ahn
Rheumatology.2025; 64(3): 1400. CrossRef
Dementia Incidence in Survivors of Multiple Myeloma: A National Case-Control Study Conducted in Korea (The CAREMM-2106 Study)
Jeonghoon Ha, Suein Choi, Seulji Moon, Jinseon Han, Jeongyoon Lee, Sung-Soo Park, Sheng-Min Wang, Seunghoon Han, Chang-Ki Min
Clinical Lymphoma Myeloma and Leukemia.2025; 25(1): e40. CrossRef
Autophagy activation in response to cigarette smoke: Exploring the disparity in laryngeal cancer incidence and outcomes between sexes in South Korea
Min Ji Kim, Jisu Hong, Hyo Won Chang, Yun-Hee Lee, Jun-Pyo Myong, Ah Ra Jung, Yoon Se Lee, Minsu Kwon
Translational Oncology.2025; 52: 102229. CrossRef
Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database
Kyung-Soo Kim, Bongseong Kim, Kyungdo Han
Diabetes & Metabolism Journal.2025; 49(1): 13. CrossRef
The impact of the COVID-19 pandemic on clinical practices related to colorectal cancer and colonoscopy in South Korea: a nationwide population-based study
Jin Young Yoon, Moon Hyung Lee, Min Seob Kwak, Jae Myung Cha
Intestinal Research.2025; 23(1): 85. CrossRef
Facilitators and Barriers to Multidisciplinary Teamwork in Adolescent and Young Adult Oncology Care: A Descriptive Qualitative Study
Hyewon Shin, Jin Young Seo, Eun Seok Choi, Jennie De Gagne
Journal of Multidisciplinary Healthcare.2025; Volume 18: 917. CrossRef
Differential Pattern of Symptom Correlation With Acute Respiratory Infections in Korea
Jinsoo Kim, Gyoohwan Jung, Soyeoun Kim
Pediatric Infectious Disease Journal.2025; 44(7): 609. CrossRef
The Impact of COVID-19 on Admissions and In-hospital Mortality of Patients With Stroke in Korea: An Interrupted Time Series Analysis
Youngs Chang, Soo-Hee Hwang, Haibin Bai, Seowoo Park, Eunbyul Cho, Dohoung Kim, Hyejin Lee, Jin Yong Lee
Journal of Preventive Medicine and Public Health.2025; 58(1): 60. CrossRef
Impact of COVID-19 on admission and in-hospital mortality of patients with acute myocardial infarction in Korea: An interrupted time series analysis
Soo-Hee Hwang, Youngs Chang, Haibin Bai, Jieun Yun, Hyejin Lee, Jin Yong Lee, Dong Keon Yon
PLOS ONE.2025; 20(2): e0316943. CrossRef
Risk of cardiovascular diseases and gastrointestinal bleeding is comparable between celecoxib and non-selective non-steroidal anti-inflammatory drugs in patients with ankylosing spondylitis: a nationwide retrospective cohort study
A Kim, SC Kim, J Kim, MW So, S-G Lee
Scandinavian Journal of Rheumatology.2025; 54(3): 204. CrossRef
Mortality and cardiovascular disease after cholecystectomy in type 2 diabetes: A nationwide longitudinal cohort study
Han Na Jung, Ji Hye Heo, Eun Roh, Kyung‐Do Han, Jun Goo Kang, Seong Jin Lee, Sung‐Hee Ihm
Journal of Hepato-Biliary-Pancreatic Sciences.2025; 32(7): 514. CrossRef
Double disparities of the excess risks and costs of extreme temperatures on hospitalization between Medical Aid and non-Medical Aid populations in South Korea
Ayoung Kim, Jinah Park, Cinoo Kang, Ho Kim, Whanhee Lee
International Journal of Epidemiology.2025;[Epub] CrossRef
Longitudinal association between consecutive moderate-to-vigorous physical activity and the risk of depression among depressed and non-depressed participants: A nationally representative cohort study
Yohwan Lim
Journal of Affective Disorders.2025; 381: 475. CrossRef
Risk of Gout Among Patients With Tuberculosis: A Nationwide Cohort Study in South Korea
Chi Young Kim, Jang Woo Ha, Inkyung Jung, Minkyung Han, Sung Soo Ahn
International Journal of Rheumatic Diseases.2025;[Epub] CrossRef
Association of Metabolic Dysfunction‐Associated Steatotic Liver Disease With Sudden Sensorineural Hearing Loss Among Older Adults
Eun Seok Kang, Seohui Jang, Hye Jun Kim, Kyuwoong Kim, Meng Sha, Yun Hwan Oh, Michelle J. Suh, Seogsong Jeong
Laryngoscope Investigative Otolaryngology.2025;[Epub] CrossRef
Association between temporomandibular disorders and mental and behavioural disorders - a nationwide population-based cross-sectional study
Younjung Park, Sora Yoon, Joon-Ho Yoon, Jin-Joo Yoo
Clinical Oral Investigations.2025;[Epub] CrossRef
Intellectual developmental disability and all-cause and cause-specific mortality among individuals with type 2 diabetes mellitus
Jun-Hyuk Lee, Yong-Moon Mark Park, Kyungdo Han, Ye-Bin Park, Bong-Seong Kim, Jin-Hyung Jung, Ga Eun Nam
Diabetes Research and Clinical Practice.2025; 226: 112305. CrossRef
The Effectiveness of Operative Fixation for Comminuted Distal Radial Fractures in the Hyper-aged Patients Over 75 Years Old in South Korea
Jisu PARK, Jaemin LEE, Jin Rok OH
The Journal of Hand Surgery (Asian-Pacific Volume).2025; 30(03): 271. CrossRef
Association between osteoporosis and mortality in Parkinson's disease with mediating effect of hip fractures: a Korean nationwide population-based study
Yeonju Jin, Bo Kyu Choi, Jong Woo Lee, Jin Yong Hong, Ickpyo Hong, Min Seok Baek
Frontiers in Aging Neuroscience.2025;[Epub] CrossRef
Association between inhaled corticosteroids and incidence of idiopathic pulmonary fibrosis: nationwide population-based study
Hyewon Lee, Hee-Young Yoon
BMJ Open Respiratory Research.2025; 12(1): e002566. CrossRef
Prescribing Patterns of SGLT2 Inhibitors and GLP‐1 Receptor Agonists in Patients With T2DM and ASCVD in South Korea
Yeong Rok Eom, Hajung Joo, Seung Eun Chae, Nam Kyung Je
Pharmacoepidemiology and Drug Safety.2025;[Epub] CrossRef
Risk of pancreatic cancer according to glycemic status in nonalcoholic fatty liver disease: a nationwide cohort study
Han Na Jung, Ji Hye Huh, Eun Roh, Bum Jun Kim, Minwoo Lee, Jwa-Kyung Kim, Joo-Hee Kim, Boram Han, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
Scientific Reports.2025;[Epub] CrossRef
Older Age Threshold for Oxaliplatin Benefit in Stage II to III Colorectal Cancer
Jun Woo Bong, Hwamin Lee, Seogsong Jeong, Sanghee Kang
JAMA Network Open.2025; 8(8): e2525660. CrossRef
Fractures incidence and its association on mortality in multiple myeloma patients: a nationwide cohort study (CAREMM-2105 study)
Jeonghoon Ha, Suein Choi, Sung-Soo Park, Seulji Moon, Jinseon Han, Jeongyoon Lee, Ki-Hyun Baek, Seunghoon Han, Chang-Ki Min
Scientific Reports.2025;[Epub] CrossRef
Patterns of spinal injections following lumbar fusion surgery: a nationwide cohort study with 3-year follow-up
Yong Jae Na, Beom Suk Kim, Woo-Keun Kwon
European Spine Journal.2025; 34(9): 4205. CrossRef
Real-World Utilization Patterns of Immune Checkpoint Inhibitors Based on the National Health Insurance Service Data in Korea
Eunji Kim, Yu-Seon Jung, Jongmin Lee, Dal Ri Nam, Seung-Hun You, Ju Won Lee, Sook Ryun Park, Ji Seon Oh, Ye-Jee Kim, Eun-Jung Jo, Nakyung Jeon, Won-Jung Jung, Sun-Young Jung
Clinical Therapeutics.2025; 47(10): 837. CrossRef
Overall survival following radical surgery and postoperative chemotherapy in colorectal cancer patients aged ≥ 70 years: a population-based retrospective cohort study
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BMC Cancer.2025;[Epub] CrossRef
Real-world evidence on the additional cancer risk reduction of ezetimibe: a 10-year nationwide retrospective cohort study emulating a target trial
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Journal of Cancer Research and Clinical Oncology.2025;[Epub] CrossRef
Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA
Ye-Jee Kim, Jiyeon Kim, Jiwon Lee, Tae Sun Shim, Sang Hyoung Park, Kyung-Wook Jo
Intestinal Research.2025; 23(4): 541. CrossRef
Triglyceride-glucose index variability and risk of all-cause and cardiovascular mortality
Jimin Park, Duk Ho Kim, Jun-Hyuk Lee
Scientific Reports.2025;[Epub] CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease and Risk of Hepatocellular Carcinoma in Type 2 Diabetes Mellitus
So Hyun Cho, Gyuri Kim, Kyu-na Lee, Rosa Oh, Ji Yoon Kim, Myunghwa Jang, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim
Diabetes & Metabolism Journal.2025; 49(6): 1298. CrossRef
Dementia in older adults with schizophrenia: a 12-year analysis of prevalence, incidence, and treatment patterns in South Korea
Jung Su Park, Sangwan Kim, Donghoon Jeong, Jeong Pil Choi, Hyunsu Jeong, Alan Jung Park, Yong Sik Kim, Joongyub Lee, Se Hyun Kim
Schizophrenia.2025;[Epub] CrossRef
Nationwide health claims analysis of phenothiazine‐associated retinopathy risk in chlorpromazine and perphenazine users
Jiyeong Kim, Jee-Eun Chung, Seong Joon Ahn
Scientific Reports.2025;[Epub] CrossRef
Impact of Type 2 Diabetes Mellitus on Age at Death in the Hemodialysis Population: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Ji Hong You, Kang Ju Son, Kyoung Sook Park, Byung-Wan Lee, Sun Ok Song
Diabetology.2025; 6(12): 145. CrossRef
Epidemiology and sociodemographic determinants of chronic temporomandibular disorders in South Korea: a nationwide population-based study
Younjung Park, Sora Yoon, Joon-Ho Yoon, Jin-Joo Yoo
BMC Oral Health.2025;[Epub] CrossRef
Comparative Cardiovascular Safety of Duloxetine and Gabapentin in Patients with Hip Osteoarthritis
Suhyeon Moon, Eunjung Choo, Yeo Jin Choi, Sooyoung Shin
Journal of Pain Research.2025; Volume 18: 6437. CrossRef
Continuity of care for patients with hypertension or diabetes mellitus reduced medical utilization, total medical costs, and cardiovascular events based on the Korean NHIS-HEALS cohort
Eun-Kyeong Yun, Jae Yong Shim, Sang-Jun Shin, Hee-Taik Kang
Nutrition, Metabolism and Cardiovascular Diseases.2025; : 104527. CrossRef
The delayed cancer treatment and economic inequality in Korea: results of common cancers by the time-to-surgery
Noorhee Son, Woo-Ri Lee, Dong-Woo Choi, Kyu-Tae Han
Epidemiology and Health.2025; 47: e2025056. CrossRef
Data profile: cancer sample cohorts (stomach, breast, colorectal, and liver) in Korea
Daewoo Pak, Suk Yong Jang, Jin-Ha Yoon, Dong Wook Kim, Jin-Won Noh, Dong-Woo Choi, Minyeong Guk, Hyeri Kim, Ju-Won Oh, Heejung Chae, Hyun-Joo Kong, Gi Hyun Kim, Ji Woong Nam, Ga Ram Lee, Dayun Park, Jehoo Jeon, Byungyoon Yun, Ki-Bong Yoo, Kui Son Choi
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Various Antihypertensive Drug Compliance Models and Cardiovascular Prognosis of People With Incidentally Detected High Blood Pressure During Health Check‐Up in Korea
Jong-Kwan Park, Sungyoun Chun, Joongmin Kim, Hancheol Lee, Ji-Yong Jang, Kyeong-Hyeon Chun, Hyeongsoo Kim, Seung-Jin Oh, Geunhee Park, Se-Jung Yoon, Peng Geng
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Medical service utilization patterns among adults with insomnia: A retrospective cohort study
Min Kyung Hyun, Jang Won Lee
European Journal of Integrative Medicine.2024; 67: 102325. CrossRef
COVID-19-related cardiovascular disease risk due to weight gain: a nationwide cohort study
Su Kyoung Lee, Yohwan Lim, Seogsong Jeong, Hyun Wook Han
European Journal of Medical Research.2024;[Epub] CrossRef
Kidney Health Plan 2033 in Korea: bridging the gap between the present and the future
Do Hyoung Kim, Young Youl Hyun, Jin Joo Cha, Sua Lee, Hyun Kyung Lee, Jong Wook Choi, Su-Hyun Kim, Sang Youb Han, Cheol Whee Park, Eun Young Lee, Dae Ryong Cha, Sung Gyun Kim, Chun Soo Lim, Sun-Hee Park
Kidney Research and Clinical Practice.2024; 43(1): 8. CrossRef
Bipolar disorder and the risk of cardiometabolic diseases, heart failure, and all-cause mortality: a population-based matched cohort study in South Korea
You-Bin Lee, Hyewon Kim, Jungkuk Lee, Dongwoo Kang, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Hong Jin Jeon, Kyu Yeon Hur
Scientific Reports.2024;[Epub] CrossRef
Evidence for the biopsychosocial model of suicide: a review of whole person modeling studies using machine learning
Earvin S. Tio, Melissa C. Misztal, Daniel Felsky
Frontiers in Psychiatry.2024;[Epub] CrossRef
Nationwide Study of the Epidemiology, Diagnosis, and Treatment of Hypersensitivity Pneumonitis in Korea
Hae In Jung, Dal Ri Nam, Seung-Hun You, Jae-Woo Jung, Kang-Mo Gu, Sun-Young Jung
Journal of Korean Medical Science.2024;[Epub] CrossRef
Quantitative risk factor analysis of prior disease condition and socioeconomic status with the multiple myeloma development: nationwide cohort study
Suein Choi, Eunjin Kim, Jinhee Jung, Sung-Soo Park, Chang-Ki Min, Seunghoon Han
Scientific Reports.2024;[Epub] CrossRef
Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study
Sungmi Kim, Jin‐Hyung Jung, Kyungho Lee, Junseok Jeon, Dong Wook Shin, Hye Ryoun Jang, Jung Eun Lee, Kyungdo Han, Wooseong Huh
Clinical Transplantation.2024;[Epub] CrossRef
Impact of an expanded reimbursement policy on utilization of implantable loop recorders in patients with cryptogenic stroke in Korea
Hye Bin Gwag, Nak Gyeong Ko, Mihyeon Jin
The Korean Journal of Internal Medicine.2024; 39(3): 469. CrossRef
Smoking status and clinical outcome in idiopathic pulmonary fibrosis: a nationwide study
Hee-Young Yoon, Hoseob Kim, Yoonjong Bae, Jin Woo Song
Respiratory Research.2024;[Epub] CrossRef
Data Resource Profile: Health Insurance Review and Assessment Service Covid-19 Observational Medical Outcomes Partnership (HIRA Covid-19 OMOP) database in South Korea
Chungsoo Kim, Dong Han Yu, Hyeran Baek, Jaehyeong Cho, Seng Chan You, Rae Woong Park
International Journal of Epidemiology.2024;[Epub] CrossRef
Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis
Min Wook So, A-Ran Kim, Seung-Geun Lee
Rheumatology and Therapy.2024; 11(4): 881. CrossRef
Body mass index is associated with clinical outcomes in idiopathic pulmonary fibrosis
Hee-Young Yoon, Hoseob Kim, Yoonjong Bae, Jin Woo Song
Scientific Reports.2024;[Epub] CrossRef
DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korea
Min Wook So, Aran Kim, Seung-Geun Lee
Medicine.2024; 103(27): e38801. CrossRef
Prescription patterns and effectiveness of medications for chronic obstructive pulmonary disease: A retrospective study of real-world settings
Hye Jung Park, Jae Uk Lee, Soyoung Jeon, Hye Sun Lee, Bo Yeon Kim, Yu Jin Chae, Gui Ok Kim, Jung-Won Park, Jae-Hyun Lee, Ai Theng Cheong
PLOS ONE.2024; 19(6): e0304362. CrossRef
High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study
Han Na Jung, Ji Hye Huh, Eun Roh, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
Lipids in Health and Disease.2024;[Epub] CrossRef
Major cardiovascular events in long-term multiple myeloma survivors: a Korean case–control study (the CAREMM-2105 study)
Jeonghoon Ha, Suein Choi, Seulji Moon, Jinseon Han, Jeongyoon Lee, Ki-Hyun Baek, Seunghoon Han, Sung-Soo Park, Chang-Ki Min
Clinical and Experimental Medicine.2024;[Epub] CrossRef
Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study
Jiyun Park, Jin-Hyung Jung, Hyunju Park, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyungdo Han, Kyung-Soo Kim
BMC Medicine.2024;[Epub] CrossRef
Big Data Research on Severe Asthma
Sang Hyuk Kim, Youlim Kim
Tuberculosis and Respiratory Diseases.2024; 87(3): 213. CrossRef
Detecting spatial heat vulnerability in the city considering spatiotemporal population distribution: A focus on the elderly during daytime
Seunghyun Lee, Jae Seung Lee, Saehoon Kim
Urban Climate.2024; 56: 102054. CrossRef
Real‐World Incidence of Incident Noninfectious Uveitis in Patients Treated With BRAF Inhibitors: A Nationwide Clinical Cohort Study
HYUNJEAN JUNG, SUNYEUP KIM, CHRISTOPHER SEUNGKYU LEE, SUK HO BYEON, SUNG SOO KIM, SEUNG WON LEE, YONG JOON KIM
American Journal of Ophthalmology.2024; 267: 142. CrossRef
Incidence of hearing loss following COVID-19 among young adults in South Korea: a nationwide cohort study
Hye Jun Kim, Seogsong Jeong, Kyuwoong Kim, Joon Don Lee, Yun Hwan Oh, Michelle J. Suh
eClinicalMedicine.2024; 75: 102759. CrossRef
Comparative risk of serious infections and tuberculosis in Korean patients with inflammatory bowel disease treated with non-anti-TNF biologics or anti-TNF-α agents: a nationwide population-based cohort study
Min Jee Kim, Ye-Jee Kim, Daehyun Jeong, Seonok Kim, Seokchan Hong, Sang Hyoung Park, Kyung-Wook Jo
Therapeutic Advances in Gastroenterology.2024;[Epub] CrossRef
Cancer risk among air transportation industry workers in Korea: a national health registry-based study
Soojin Park, Ga Bin Lee, Dalnim Lee, Eun-Shil Cha, Kyunghee Han, Minsu Cho, Songwon Seo
BMC Public Health.2024;[Epub] CrossRef
The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea
So Hee Kang, Yun-Hee Lee, Jun-Pyo Myong, Minsu Kwon
Cancer Research and Treatment.2024; 56(4): 1077. CrossRef
Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study
Si Nae Oh, Hye Jun Kim, Jae Yong Shim, Kyuwoong Kim, Seogsong Jeong, Sun Jae Park, Sang Hyun Lee, Joong Won Ha, Sang Min Park
Scientific Reports.2024;[Epub] CrossRef
Impact of mental disorders on the all-cause mortality and cardiovascular disease outcomes in adults with new-onset type 1 diabetes: A nationwide cohort study
Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Psychiatry Research.2024; 342: 116228. CrossRef
Nationwide study of chronic codeine use and its impact on cough related diseases in South Korea
Tai Joon An, Yun-Hee Lee, Joon-Sung Joh, Jun-Pyo Myong
Scientific Reports.2024;[Epub] CrossRef
Association of age at menopause and suicide risk in postmenopausal women: a nationwide cohort study
Daa Un Moon, Hyewon Kim, Jin-Hyung Jung, Kyungdo Han, Hong Jin Jeon
Frontiers in Psychiatry.2024;[Epub] CrossRef
Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer?
Hoon Kim, Hyun Jung Kim, Hyeong Sik Ahn
Gynecologic Oncology.2023; 169: 147. CrossRef
Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus
Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
Diabetes & Metabolism Journal.2023; 47(1): 45. CrossRef
Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study
Junghyun Noh, Min Kyong Moon, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
Diabetes & Metabolism Journal.2023; 47(1): 59. CrossRef
Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea
Seung-Hwan Lee, Jin Yu, Kyungdo Han, Seung Woo Lee, Sang Youn You, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim
Endocrinology and Metabolism.2023; 38(1): 129. CrossRef
Genital tract infection and pelvic surgery contribute to the development of endometriosis
Ae Ra Han, Suehyun Lee, Jaehun Cha, Jong-Yeup Kim, Dong-Kyu Kim, Jae Won Han, Chul Jung Kim, Sung Ki Lee
Journal of Reproductive Immunology.2023; 156: 103831. 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
Comorbidity Differences by Trajectory Groups as a Reference for Identifying Patients at Risk for Late Mortality in Childhood Cancer Survivors: Longitudinal National Cohort Study
Hyery Kim, Hae Reong Kim, Sung Han Kang, Kyung-Nam Koh, Ho Joon Im, Yu Rang Park
JMIR Public Health and Surveillance.2023; 9: e41203. CrossRef
Investigation of the Relationship Between Psychiatry Visit and Suicide After Deliberate Self-harm: Longitudinal National Cohort Study
Hye Hyeon Kim, Chanyoung Ko, Ji Ae Park, In Han Song, Yu Rang Park
JMIR Public Health and Surveillance.2023; 9: e41261. CrossRef
Long-term exposure to particulate matter and risk of Alzheimer’s disease and vascular dementia in Korea: a national population-based Cohort Study
Jung-Im Shim, Garam Byun, Jong-Tae T. Lee
Environmental Health.2023;[Epub] CrossRef
Association of Physical Activity With SARS-CoV-2 Infection and Severe Clinical Outcomes Among Patients in South Korea
YoHwan Lim, Myeong Hoon Lee, Seogsong Jeong, Hyun Wook Han
JAMA Network Open.2023; 6(4): e239840. CrossRef
Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
Journal of Clinical Medicine.2023; 12(9): 3160. CrossRef
Nationwide patterns of hydroxychloroquine dosing and monitoring of retinal toxicity in patients with systemic lupus erythematosus
Jae-Eun Lee, Dal Ri Nam, Yoon-Kyoung Sung, Yu Jeong Kim, Sun-Young Jung
Scientific Reports.2023;[Epub] CrossRef
Associations of updated cardiovascular health metrics, including sleep health, with incident diabetes and cardiovascular events in older adults with prediabetes: A nationwide population-based cohort study
Kyoung Hwa Ha, Dae Jung Kim, Seung Jin Han
Diabetes Research and Clinical Practice.2023; 203: 110820. CrossRef
Association of Socioeconomic Status With Long-Term Outcome in Survivors After Out-of-Hospital Cardiac Arrest: Nationwide Population-Based Longitudinal Study
Kyung Hun Yoo, Yongil Cho, Jaehoon Oh, Juncheol Lee, Byuk Sung Ko, Hyunggoo Kang, Tae Ho Lim, Sang Hwan Lee
JMIR Public Health and Surveillance.2023; 9: e47156. CrossRef
Antimicrobial and Antibiofilm Effects of Lactiplantibacillus plantarum THK-j112 Isolated from Kimchi against Streptococcus mutans
Du-Na Yu, Eun-Ji Yi, Je-Yong Jung, Tae-Hoo Yi, Moochang Kook
Current Topic in Lactic Acid Bacteria and Probiotics.2023; 9(1): 9. CrossRef
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 & Metabolism Journal.2023; 47(4): 514. CrossRef
Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: A population‐based cohort study
Eun Jeong Gong, Hye‐Kyung Jung, Bora Lee, Jitaek Hong, Jong Wook Kim, Cheol Min Shin, Young Hoon Youn, Kwang Jae Lee
Alimentary Pharmacology & Therapeutics.2023; 58(7): 668. CrossRef
Risk Factors for Lower Extremity Amputation in Patients with End-Stage Kidney Disease: A Nationwide Cohort Study
Min Jun Seo, Dong Geon Lee, Se Yun Ko, Ga Yeong Song, Geon Yeong Lee, Sung Hwa Kim, Dae Ryong Kang, Jiye Kim, Jun Young Lee
Journal of Clinical Medicine.2023; 12(17): 5641. CrossRef
Poorer outcomes following COVID-19 infection for patients with depression: A cohort analysis in South Korea
Su Kyoung Lee, Yohwan Lim, Seogsong Jeong, Hyun Wook Han
Annals of the Academy of Medicine, Singapore.2023; 52(8): 411. CrossRef
The role of income and frequency of dental visits in the relationship between dental sealant use and resin fillings after extended coverage: a retrospective cohort study
Dong-Hun Han, Hee-Yeon Kang, Jae-In Ryu
BMC Oral Health.2023;[Epub] CrossRef
Effect of changes in the hearing aid subsidy on the prevalence of hearing loss in South Korea
Chul Young Yoon, Junhun Lee, Tae Hoon Kong, Young Joon Seo
Frontiers in Neurology.2023;[Epub] CrossRef
Visual Impairment Risk After Alcohol Abstinence in Patients With Newly Diagnosed Open-Angle Glaucoma
Yoon Jeong, Su Hwan Kim, Goneui Kang, Hyung-Jin Yoon, Young Kook Kim, Ahnul Ha
JAMA Network Open.2023; 6(10): e2338526. CrossRef
Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study
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Brief Report

Complications
Diabetic Retinopathy and Related Clinical Practice for People with Diabetes in Korea: A 10-Year Trend Analysis: Yoo-Ri Chung, Kyoung Hwa Ha, Kihwang Lee, Dae Jung Kim; Diabetes Metab J. 2020;44(6):928-932. Published online July 10, 2020; DOI: https://doi.org/10.4093/dmj.2020.0096

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We performed a retrospective cohort study including people diagnosed with diabetes from 2006 to 2015 according to the Korean National Health Insurance Service-National Sample Cohort database, to analyze the changes in the prevalence, screening rate, and treatment patterns for diabetic retinopathy (DR) over 10 years. The proportion of people who underwent fundus screening for DR steadily increased over the past decade. The prevalence of DR increased from 13.4% in 2006 to 15.9% in 2015, while that of proliferative DR steadily decreased from 1.29% in 2006 to 1.16% in 2015. The proportion of patients undergoing retinal photocoagulation constantly decreased. The prevalence of DR increased over the past decade, while its severity seemed to have improved, with a decreased rate of proliferative DR and retinal photocoagulation. A higher proportion of patients underwent ophthalmic screening using fundus examination, but still less than 30% of patients with diabetes underwent comprehensive examination in 2015.

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Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021
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Original Articles

Basic Research
MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice: Hui Ran, Yao Lu, Qi Zhang, Qiuyue Hu, Junmei Zhao, Kai Wang, Xuemei Tong, Qing Su; Diabetes Metab J. 2021;45(3):439-451. Published online May 18, 2020; DOI: https://doi.org/10.4093/dmj.2019.0212; Correction in: Diabetes Metab J 2021;45(5):797 Correction in: Diabetes Metab J 2025;49(2):331

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Background

Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear.

Methods

We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle.

Results

MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake.

Conclusion

MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.

Citations

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Mondo family proteins in diabetes
Sandeep Kumar Barodia, Maria B. Grant, Marina S. Gorbatyuk
Frontiers in Endocrinology.2026;[Epub] CrossRef
The Function of MondoA and ChREBP Nutrient—Sensing Factors in Metabolic Disease
Byungyong Ahn
International Journal of Molecular Sciences.2023; 24(10): 8811. CrossRef
Normal and Neoplastic Growth Suppression by the Extended Myc Network
Edward V. Prochownik, Huabo Wang
Cells.2022; 11(4): 747. CrossRef
The Role of Mondo Family Transcription Factors in Nutrient-Sensing and Obesity
Huiyi Ke, Yu Luan, Siming Wu, Yemin Zhu, Xuemei Tong
Frontiers in Endocrinology.2021;[Epub] CrossRef

Complications
Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice: Wenya Weng, Tingwen Ge, Yi Wang, Lulu He, Tinghao Liu, Wanning Wang, Zongyu Zheng, Lechu Yu, Chi Zhang, Xuemian Lu; Diabetes Metab J. 2020;44(4):566-580. Published online May 15, 2020; DOI: https://doi.org/10.4093/dmj.2019.0089

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Background

Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN.

Methods

Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups.

Results

The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression.

Conclusion

Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.

Citations

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Yachan Gao, Xinxin Pang, Huichao Zhang, Dongdong Li, Jiarui Han, Zhenyi Chen, Xiaoyong Chen, Dongyang Li
Frontiers in Physiology.2026;[Epub] CrossRef
FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle
Yudie Zhang, Fan Wang, Chongyang Zhang, Fan Yao, Bin Zhang, Yongping Zhang, Xiaobo Sun
Frontiers in Pharmacology.2025;[Epub] CrossRef
The Role of Sirtuins in Diabetic Nephropathy: A Comprehensive Review
Pranay Wal, Tarannum Tarannum, Lalji Baldaniya, Kiranjeet Kaur, Priyanka Singh, Namra Aziz, Komal Singh, Amin Gasmi
Current Protein & Peptide Science.2025; 26(6): 407. CrossRef
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Anton I. Korbut, Vyacheslav V. Romanov, Vadim V. Klimontov
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David M. Ornitz, Nobuyuki Itoh
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Wenxiu Qi, Cheng Hu, Daqing Zhao, Xiangyan Li
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Min-Qi Jia, Cha-Xiang Guan, Jia-Hao Tao, Yong Zhou, Liang-Jun Yan
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Metabolic-associated fatty liver disease increases the risk of end-stage renal disease in patients with biopsy-confirmed diabetic nephropathy: a propensity-matched cohort study
Yutong Zou, Lijun Zhao, Junlin Zhang, Yiting Wang, Yucheng Wu, Honghong Ren, Tingli Wang, Yuancheng Zhao, Huan Xu, Lin Li, Nanwei Tong, Fang Liu
Acta Diabetologica.2022; 60(2): 225. CrossRef
FGF21 and Chronic Kidney Disease
João Victor Salgado, Miguel Angelo Goes, Natalino Salgado Filho
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Junyu Deng, Ye Liu, Yiqiu Liu, Wei Li, Xuqiang Nie
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Therapeutic effect and mechanism of combined use of FGF21 and insulin on diabetic nephropathy
Fanrui Meng, Yukai Cao, Mir Hassan Khoso, Kai Kang, Guiping Ren, Wei Xiao, Deshan Li
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FGF19 and FGF21 for the Treatment of NASH—Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human
Emma Henriksson, Birgitte Andersen
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FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases
Erik J. Tillman, Tim Rolph
Frontiers in Endocrinology.2020;[Epub] CrossRef

Complications
Deterioration of Sleep Quality According to Glycemic Status: Myung Haeng Hur, Mi-Kyoung Lee, Kayeon Seong, Jun Hwa Hong; Diabetes Metab J. 2020;44(5):679-686. Published online April 17, 2020; DOI: https://doi.org/10.4093/dmj.2019.0125

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Background

Type 2 diabetes mellitus (T2DM) is a progressive disease with multiple complications. The present study aimed to determine the effects of glycemic status on sleep quality in individuals with T2DM, prediabetes, and normal glucose tolerance (NGT).

Methods

A total of 90 participants were categorized into three groups, T2DM (n=30), prediabetes (n=30), and NGT (n=30). Objective sleep quality was measured with the actigraph wrist-worn device over 3 nights and subjective sleep quality was evaluated with a questionnaire.

Results

The duration of diabetes in the T2DM group was 2.23 years and the glycosylated hemoglobin (HbA1c) levels in the T2DM, prediabetes, and NGT groups were 7.83%, 5.80%, and 5.31%, respectively. Sleep efficiency decreased across the T2DM, prediabetes, and NGT groups (86.25%, 87.99%, and 90.22%, respectively; P=0.047). Additionally, HbA1c levels revealed a significant negative correlation with sleep efficiency (r=−0.348, P=0.001). The sleep quality questionnaire results were similar among the three groups.

Conclusion

Although the participants in the present study were not necessarily conscious of their sleep disturbances, deterioration in sleep quality progressed according to glycemic status.

Citations

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Monik Chaudhry, Mohit Kumar, Vatsal Singhal, Bhuvan Srinivasan
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Influence of sleep quality and other associated factors on glycemic control among diabetic patients: A hospital-based study
Sonia Mushtaq, Yusra Amin, Rukhsana Taj, Umara Giyas, Sunil Sachadev
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Alix Covenant, Thomas Yates, Alex V. Rowlands, Paddy C. Dempsey, Charlotte L. Edwardson, Andrew P. Hall, Melanie J. Davies, Joseph Henson
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Metabolic Risk/Epidemiology
Association between the Thigh Muscle and Insulin Resistance According to Body Mass Index in Middle-Aged Korean Adults: Ji Eun Heo, Jee-Seon Shim, Hokyou Lee, Hyeon Chang Kim; Diabetes Metab J. 2020;44(3):446-457. Published online April 16, 2020; DOI: https://doi.org/10.4093/dmj.2019.0110

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Background

We examined the associations between thigh muscle area (TMA) and insulin resistance (IR) according to body mass index (BMI) in middle-aged Korean general population.

Methods

TMA was measured using quantitative computed tomography and corrected by body weight (TMA/Wt) in 1,263 men, 788 premenopausal women, and 1,476 postmenopausal women all aged 30 to 64 years. The tertiles of TMA/Wt were calculated separately for men and for premenopausal and postmenopausal women. Homeostatic model assessment for insulin resistance (HOMA-IR) was performed using fasting blood glucose and insulin levels, and increased IR was defined according to sex-specific, top quartiles of HOMA-IR. Associations between the TMA/Wt tertiles and increased IR according to the BMI categories (<25 and ≥25 kg/m²) were assessed using multivariable logistic regression analysis.

Results

In men with higher BMIs, but not in those with lower BMIs, the presence of an increased IR had significantly higher odds ratios in the lower TMA/Wt tertiles, even after adjustment for visceral fat area. However, in premenopausal and postmenopausal women, there was no significant inverse association between TMA/Wt tertiles and increased IR, regardless of BMI category.

Conclusion

Our findings suggest that the thigh muscle is inversely associated with IR in men, particularly in those with higher BMIs.

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Metabolic Risk/Epidemiology
A Comparison of Predictive Performances between Old versus New Criteria in a Risk-Based Screening Strategy for Gestational Diabetes Mellitus: Subeen Hong, Seung Mi Lee, Soo Heon Kwak, Byoung Jae Kim, Ja Nam Koo, Ig Hwan Oh, Sohee Oh, Sun Min Kim, Sue Shin, Won Kim, Sae Kyung Joo, Errol R. Norwitz, Souphaphone Louangsenlath, Chan-Wook Park, Jong Kwan Jun, Joong Shin Park; Diabetes Metab J. 2020;44(5):726-736. Published online April 13, 2020; DOI: https://doi.org/10.4093/dmj.2019.0126

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Background

The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria.

Methods

This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach.

Results

Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P<0.001).

Conclusion

Compared with the old criteria, use of the new criteria would have decreased the number of patients identified as high risk and thus requiring early GDM screening by half (from 244 [29.8%] to 131 [16.0%]).

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Brief Report

Drug/Regimen
Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice: Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park; Diabetes Metab J. 2020;44(1):186-192. Published online October 31, 2019; DOI: https://doi.org/10.4093/dmj.2018.0271

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Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.

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Original Articles

Basic Research
Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT: Sundong Lin, Lechu Yu, Yongqing Ni, Lulu He, Xiaolu Weng, Xuemian Lu, Chi Zhang; Diabetes Metab J. 2020;44(1):158-172. Published online October 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0235

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Background

Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.

Methods

Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.

Results

DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).

Conclusion

FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.

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Technology/Device
Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy: In-Hwa Park, Yi-Sun Song, Hyun-Woo Joo, Guang-Yin Shen, Jin-Hee Seong, Na-Kyoung Shin, Young Jong Cho, Yonggu Lee, Jeong Hun Shin, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim; Diabetes Metab J. 2020;44(1):173-185. Published online April 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0211

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Background

Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.

Methods

Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.

Results

G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.

Conclusion

Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.

Citations

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Obesity and Metabolic Syndrome
The Risk of Myocardial Infarction and Ischemic Stroke According to Waist Circumference in 21,749,261 Korean Adults: A Nationwide Population-Based Study: Jung-Hwan Cho, Eun-Jung Rhee, Se-Eun Park, Hyemi Kwon, Jin-Hyung Jung, Kyung-Do Han, Yong-Gyu Park, Hye Soon Park, Yang-Hyun Kim, Soon-Jib Yoo, Won-Young Lee; Diabetes Metab J. 2019;43(2):206-221. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0039

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Background

Waist circumference (WC) is a well-known obesity index that predicts cardiovascular disease (CVD). We studied the relationship between baseline WC and development of incident myocardial infarction (MI) and ischemic stroke (IS) using a nationwide population-based cohort, and evaluated if its predictability is better than body mass index (BMI).

Methods

Our study included 21,749,261 Koreans over 20 years of age who underwent the Korean National Health Screening between 2009 and 2012. The occurrence of MI or IS was investigated until the end of 2015 using National Health Insurance Service data.

Results

A total of 127,289 and 181,637 subjects were newly diagnosed with MI and IS. The incidence rate and hazard ratio of MI and IS increased linearly as the WC level increased, regardless of adjustment for BMI. When the analyses were performed according to 11 groups of WC, the lowest risk of MI was found in subjects with WC of 70 to 74.9 and 65 to 69.9 cm in male and female, and the lowest risk of IS in subjects with WC of 65 to 69.9 and 60 to 64.9 cm in male and female, respectively. WC showed a better ability to predict CVD than BMI with smaller Akaike information criterion. The optimal WC cutoffs were 84/78 cm for male/female for predicting MI, and 85/78 cm for male/female for predicting IS.

Conclusion

WC had a significant linear relationship with the risk of MI and IS and the risk began to increase from a WC that was lower than expected.

Citations

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Reviews

Complications
Pathophysiology of Diabetic Retinopathy: The Old and the New: Sentaro Kusuhara, Yoko Fukushima, Shuntaro Ogura, Naomi Inoue, Akiyoshi Uemura; Diabetes Metab J. 2018;42(5):364-376. Published online October 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0182

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Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

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Expanding the horizon of oculomics: A narrative review on the emerging roles of the anterior segment and mobile health
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Protective effect of Humic acid against Diabetic Retinopathy in streptozotocin-induced diabetic rats
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Custom Deep Learning Framework for Interpreting Diabetic Retinopathy in Healthcare Diagnostics
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Stratified choroidal vascular structure in treatment-naïve diabetic retinopathy
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Foveal avascular zone area measurement in diabetic patients: Superficial, deep or combined retinal vascular complex?
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N 6-Methyladenosine Demethylase FTO Controls Macrophage Homeostasis in Diabetic Vasculopathy
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Diabetes.2025; 74(1): 82. CrossRef
HDAC6 mediates NLRP3 inflammasome activation in the pathogenesis of diabetic retinopathy
Jun-Sik Kim, Jae Hyun Jun, Jeongmi Lee, Sunyoung Park, Eunae Kim, Su Jung Hwang, Heesu Moon, Seung Hyun Baek, Hark Kyun Kim, Jinsu Park, Yoonsuk Cho, Jihoon Han, Chanhee Kim, Jongho Kim, Hyun-Mo Yang, Changsik Lee, Yeonseok Chung, Hyo-Jong Lee, Dong-Gyu J
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Impact of duration of treatments with metformin and sulfonylureas, individually or in combination, on diabetic retinopathy among newly diagnosed type 2 diabetic patients: a pooled cohort’s analysis
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Activated Growth Factor From Platelets as Treatment for Diabetic Retinopathy Through Antioxidant-Oxidative Stress Pathway
Ramzi Amin, Rachmat Hidayat, Ziske Maritska, Trisa Putri
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 305. CrossRef
NLRP3 inflammasomes pathway: a key target for Metformin
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Cd248a regulates pericyte development and viability in zebrafish
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Targeting therapy of PI3K/AKT signaling pathway via non-coding RNAs in diabetic retinopathy
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Novel Therapeutic Approaches for Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration
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Increased fatty acid-binding protein 4 levels are associated with the risk of developing retinopathy in type 2 diabetes mellitus patients
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Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab
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Automated detection of hard exudates in retinal fundus images for diabetic retinopathy screening using textural-based radon transform and morphology reconstruction
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Switching to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular edema: a systematic review and meta-analysis
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Inhibition of Endothelial HIF-1α by IDF-11774 Attenuates Retinal Neovascularization and Vascular Leakage
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Fenofibrate and Diabetic Retinopathy
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Anthocyanin-Rich Berries and Their Bioactive Compounds in Ocular Health: Mechanisms and Therapeutic Potential
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Transpupillary in vivo two-photon imaging reveals enhanced surveillance of retinal microglia in diabetic mice
Noriyuki Sotani, Sentaro Kusuhara, Ryuto Nishisho, Hiroto Kuno, Hidenori Shima, Koichiro Haruwaka, Yuka Mori, Maya Kishi, Tomoyuki Furuyashiki, Kenta Kobayashi, Hiroaki Wake, Toru Takumi, Makoto Nakamura, Yoshihisa Tachibana
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Evidence Supporting Autotaxin as a Potential New Drug Treatment Target in Patients With Advanced Diabetic Retinopathy
Harumasa Yokota, Hiroki Hayashi, Hironori Nakagami, Akifumi Kushiyama, Junya Hanaguri, Megumi Honjo, Makoto Aihara, Makoto Kurano, Koji Igarashi, Sakura Kushiyam, Satoru Yamagami, Taiji Nagaoka
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Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis
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Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip
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Serum vitamin D is substantially reduced and predicts flares in diabetic retinopathy patients
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RG7774 (Vicasinabin), an orally bioavailable cannabinoid receptor 2 (CB2R) agonist, decreases retinal vascular permeability, leukocyte adhesion, and ocular inflammation in animal models
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Diabetic retinopathy incidence, predictors and its association with longitudinal fasting blood sugar level changes among diabetes mellitus patients in Ethiopia: joint model
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Relationship between VEGF expression and ganglion and photoreceptor cell densities in diabetic retinal layers
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Health Utility Values Among Patients With Diabetic Retinopathy, Wet Age-Related Macular Degeneration, and Cataract in Thailand: A Multicenter Survey Using Time Trade-Off, EQ-5D-5L, and Health Utility Index 3
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Vitamin D levels and risk of ocular disorders: insights from bidirectional and multivariable Mendelian randomization analysis
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Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage
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Prevalence and its associated factors of diabetic retinopathy among type 1 and type 2 diabetic patients at public hospitals in Eastern Ethiopia, 2023: a hospital-based comparative cross-sectional study
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Advanced drug delivery strategies for diabetic retinopathy: current therapeutic advancement, and delivery methods overcoming barriers, and experimental modalities
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Real-World Outcomes After Switch From Aflibercept to Faricimab in Eyes With Diabetic Macular Edema
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Comparison of retrobulbar circulation in type 2 diabetics and non-diabetics using color Doppler imaging
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Indian Journal of Clinical and Experimental Ophthalmology.2024; 10(4): 655. CrossRef
Diabetic Retinopathy Requiring Vitrectomy: Epidemiology and Pathology
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Pharmacological mechanism and clinical study of Qiming granules in treating diabetic retinopathy based on network pharmacology and literature review
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Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases
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Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy
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Pathophysiology and diagnosis of diabetic retinopathy: a narrative review
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Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases
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Downregulation of plasma microRNA-29c-3p expression may be a new risk factor for diabetic retinopathy
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Short-Term Outcomes of Intravitreal Faricimab Injection for Diabetic Macular Edema
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L-type calcium channel blocker increases VEGF concentrations in retinal cells and human serum
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Efficacy and safety of curcumin in diabetic retinopathy: A protocol for systematic review and meta-analysis
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Highly water-soluble diacetyl chrysin ameliorates diabetes-associated renal fibrosis and retinal microvascular abnormality in db/db mice
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Preventive and management approach of triptonide, a diterpenoid compound against streptozotocin-induced diabetic retinopathy in Wistar rat model
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New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy
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Evaluation of Social Platform-Based Continuity of Care in Improving Cognitive and Prognostic Effects of Young Patients with Diabetic Retinopathy
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Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value
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The rs1800469 T/T and rs1800470 C/C genotypes of the TGFB1 gene confer protection against diabetic retinopathy in a Southern Brazilian population
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Diabetes mellitus and its influence on the incidence and process of diabetic retinopathy
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Dysregulation of the NLRP3 Inflammasome in Diabetic Retinopathy and Potential Therapeutic Targets
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Adult-induced genetic ablation distinguishes PDGFB roles in blood-brain barrier maintenance and development
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Investigation on the Q-markers of Bushen Huoxue Prescriptions for DR treatment based on chemometric methods and spectrum-effect relationship
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Corneal Confocal Microscopy in Type 1 Diabetes Mellitus: A Six-Year Longitudinal Study
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Long-Term Oral Administration of Salidroside Alleviates Diabetic Retinopathy in db/db Mice
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Chorioretinal Hypoxia Detection Using Lipid-Polymer Hybrid Organic Room-Temperature Phosphorescent Nanoparticles
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LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis
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Correlation between the progression of diabetic retinopathy and inflammasome biomarkers in vitreous and serum – a systematic review
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Clinical Diabetes & Therapeutics
Diabetes and Subclinical Coronary Atherosclerosis: Chang Hoon Lee, Seung-Whan Lee, Seong-Wook Park; Diabetes Metab J. 2018;42(5):355-363. Published online October 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0041

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Abstract PDF PubReader ePub

It is well known that diabetic patients have a high risk of cardiovascular events, and although there has been a tremendous effort to reduce these cardiovascular risks, the incidence of cardiovascular morbidity and mortality in diabetic patients remains high. Therefore, the early detection of coronary artery disease (CAD) is necessary in those diabetic patients who are at risk of cardiovascular events. Significant medical and radiological advancements, including coronary computed tomography angiography (CCTA), mean that it is now possible to investigate the characteristics of plaques, instead of solely evaluating the calcium level of the coronary artery. Recently, several studies reported that the prevalence of subclinical coronary atherosclerosis (SCA) is higher than expected, and this could impact on CAD progression in asymptomatic diabetic patients. In addition, several reports suggest the potential benefit of using CCTA for screening for SCA in asymptomatic diabetic patients, which might dramatically decrease the incidence of cardiovascular events. For these reasons, the medical interest in SCA in diabetic patients is increasing. In this article, we sought to review the results of studies on CAD in asymptomatic diabetic patients and discuss the clinical significance and possibility of using CCTA to screen for SCA.

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Brief Report

Others
Serum Soluble Epidermal Growth Factor Receptor Level Increase in Patients Newly Diagnosed with Type 2 Diabetes Mellitus: Ji Min Kim, Sorim Choung, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2018;42(4):343-347. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0082

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We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.

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Original Articles

Complications
Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome: Kwi-Hyun Bae, Sung Woo Kim, Yeon-Kyung Choi, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Won Kee Lee, Sungwoo Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park; Diabetes Metab J. 2018;42(3):207-214. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0081

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Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.

Methods

From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.

Results

Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.

Conclusion

Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Citations

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Letter: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
Jin Hwa Kim
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Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
Sung Woo Kim, Keun-Gyu Park
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Complications
Color Doppler Ultrasonography Is a Useful Tool for Diagnosis of Peripheral Artery Disease in Type 2 Diabetes Mellitus Patients with Ankle-Brachial Index 0.91 to 1.40: Kyu Yeon Hur, Ji Eun Jun, Young Ju Choi, Yong-ho Lee, Dae Jung Kim, Seok Won Park, Byung Wook Huh, Eun Jig Lee, Sun-Ha Jee, Kap Bum Huh, Sung Hee Choi; Diabetes Metab J. 2018;42(1):63-73. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.63

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Background

The clinical utility of ankle-brachial index (ABI) is not clear in subjects with less severe or calcified vessel. Therefore, we investigated the usefulness of color Doppler ultrasonography for diagnosing peripheral artery disease (PAD) in type 2 diabetes mellitus (T2DM) subjects.

Methods

We analyzed 324 T2DM patients who concurrently underwent ABI and carotid intima-media thickness (CIMT) measurements and color Doppler ultrasonography from 2003 to 2006. The degree of stenosis in patients with PAD was determined according to Jager's criteria, and PAD was defined as grade III (50% to 99% stenosis) or IV stenosis (100% stenosis) by color Doppler ultrasonography. Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the risk factors for PAD in patients with ABI 0.91 to 1.40.

Results

Among the 324 patients, 77 (23.8%) had ABI 0.91 to 1.40 but were diagnosed with PAD. Color Doppler ultrasonography demonstrated that suprapopliteal arterial stenosis, bilateral lesions, and multivessel involvement were less common in PAD patients with ABI 0.91 to 1.40 than in those with ABI ≤0.90. A multivariate logistic regression analysis demonstrated that older age, current smoking status, presence of leg symptoms, and high CIMT were significantly associated with the presence of PAD in patients with ABI 0.91 to 1.40 after adjusting for conventional risk factors. CIMT showed significant power in predicting the presence of PAD in patients with ABI 0.91 to 1.40.

Conclusion

Color Doppler ultrasonography is a useful tool for the detection of PAD in T2DM patients with ABI 0.91 to 1.40 but a high CIMT.

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Reviews

Clinical Diabetes & Therapeutics
The Effectiveness of Green Tea or Green Tea Extract on Insulin Resistance and Glycemic Control in Type 2 Diabetes Mellitus: A Meta-Analysis: Jinyue Yu, Peige Song, Rachel Perry, Chris Penfold, Ashley R. Cooper; Diabetes Metab J. 2017;41(4):251-262. Published online August 22, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.4.251

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Green tea or green tea extract (GT/GTE) has been demonstrated to reduce insulin resistance and improve glycemic control. However, evidence for this health beneficial effect is inconsistent. This systematic review evaluated the effect of GT/GTE on insulin resistance and glycemic control in people with pre-diabetes/type 2 diabetes mellitus (T2DM). Ovid MEDLINE, Embase, AMED, Web of Science, and the Cochrane Library were searched up to April 2017 for randomised controlled trials of participants with pre-diabetes or T2DM, where the intervention was GT/GTE. Meta-analysis was performed to assess the standardised mean difference (SMD) in biomarkers of insulin resistance and glycemic control between GT/GTE and placebo groups. Six studies (n=382) were pooled into random-effects meta-analysis. Overall, no differences were found between GT/GTE and the placebo for glycosylated hemoglobin (HbA1c: SMD, −0.32; 95% confidence interval [CI], −0.86 to 0.23), homeostatic model assessment for insulin resistance (HOMA-IR: SMD, 0.10; 95% CI, −0.17 to 0.38), fasting insulin (SMD, −0.25; 95% CI, −0.64 to 0.15), and fasting glucose (SMD, −0.10; 95% CI, −0.50 to 0.30). No evidence support the consumption of GT/GTE could reduce the levels of HbA1c, HOMA-IR, fasting insulin, or fasting glucose in people with pre-diabetes/T2DM. However, the studies included were small and of varying quality.

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Clinical Care/Education
A Clinical Practice Guideline to Guide a System Approach to Diabetes Care in Hong Kong: Ip Tim Lau; Diabetes Metab J. 2017;41(2):81-88. Published online April 14, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.2.81

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Abstract PDF PubReader ePub

The Hospital Authority of Hong Kong is a statutory body that manages all the public medical care institutions in Hong Kong. There are currently around 400,000 diabetic patients under its care at 17 hospitals (providing secondary care for 40%) and 73 General Outpatient Clinics (providing primary care for 60%). The patient population has been growing at 6% to 8% per year over the past 5 years, estimated to include over 95% of all diagnosed patients in Hong Kong. In order to provide equitable and a minimal level of care within resources and local system factors constraints, a Clinical Practice Guideline on the management of type 2 diabetes mellitus was drawn in 2013 to guide a system approach to providing diabetes care. There is an algorithm for the use of various hypoglycemic agents. An organizational drug formulary governs that less expansive options have to be used first. A number of clinical care and patient empowerment programs have been set up to support structured and systematic diabetes care. With such a system approach, there have been overall improvements in diabetes care with the percentage of patients with glycosylated hemoglobin <7% rising from 40% in 2010 to 52% in 2015.

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Age‐Specific Associations Between Systolic Blood Pressure and Cardiovascular Disease: A 10‐Year Diabetes Mellitus Cohort Study
Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Ian Chi Kei Wong, Esther Wai Yin Chan, Shiqi Chen, Cindy Lo Kuen Lam
Journal of the American Heart Association.2020;[Epub] CrossRef
Associations between usual glycated haemoglobin and cardiovascular disease in patients with type 2 diabetes mellitus: A 10‐year diabetes cohort study
Eric YF Wan, Esther YT Yu, Julie Y Chen, Ian CK Wong, Esther WY Chan, Cindy LK Lam
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Cultural adaptation and psychometric properties of the Chinese Burden of Treatment Questionnaire (C-TBQ) in primary care patients with multi-morbidity
Weng Yee Chin, Carlos King Ho Wong, Cherry Cheuk Wai Ng, Edmond Pui Hang Choi, Cindy Lo Kuen Lam
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Association of Blood Pressure and Risk of Cardiovascular and Chronic Kidney Disease in Hong Kong Hypertensive Patients
Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Daniel Yee Tak Fong, Edmond Pui Hang Choi, Cindy Lo Kuen Lam
Hypertension.2019; 74(2): 331. CrossRef
Burden of CKD and Cardiovascular Disease on Life Expectancy and Health Service Utilization: a Cohort Study of Hong Kong Chinese Hypertensive Patients
Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Daniel Yee Tak Fong, Edmond Pui Hang Choi, Eric Ho Man Tang, Cindy Lo Kuen Lam
Journal of the American Society of Nephrology.2019; 30(10): 1991. CrossRef
Effect of Achieved Systolic Blood Pressure on Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Population-Based Retrospective Cohort Study
Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Colman Siu Cheung Fung, Daniel Yee Tak Fong, Edmond Pui Hang Choi, Anca Ka Chun Chan, Cindy Lo Kuen Lam
Diabetes Care.2018; 41(6): 1134. CrossRef
Evolution of Diabetes Care in Hong Kong: From the Hong Kong Diabetes Register to JADE-PEARL Program to RAMP and PEP Program
Ivy H.Y. Ng, Kitty K.T. Cheung, Tiffany T.L. Yau, Elaine Chow, Risa Ozaki, Juliana C.N. Chan
Endocrinology and Metabolism.2018; 33(1): 17. CrossRef
Relation between HbA1c and incident cardiovascular disease over a period of 6 years in the Hong Kong population
E.Y.F. Wan, E.Y.T. Yu, C.S.C. Fung, W.Y. Chin, D.Y.T. Fong, A.K.C. Chan, C.L.K. Lam
Diabetes & Metabolism.2018; 44(5): 415. CrossRef
Five-Year Effectiveness of the Multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) on Diabetes-Related Complications and Health Service Uses—A Population-Based and Propensity-Matched Cohort Study
Eric Yuk Fai Wan, Colman Siu Cheung Fung, Fang Fang Jiao, Esther Yee Tak Yu, Weng Yee Chin, Daniel Yee Tak Fong, Carlos King Ho Wong, Anca Ka Chun Chan, Karina Hiu Yen Chan, Ruby Lai Ping Kwok, Cindy Lo Kuen Lam
Diabetes Care.2018; 41(1): 49. CrossRef
Do We Need a Patient-Centered Target for Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes Mellitus?
Eric Yuk Fai Wan, Esther Yee Tak Yu, Colman Siu Cheung Fung, Weng Yee Chin, Daniel Yee Tak Fong, Anca Ka Chun Chan, Cindy Lo Kuen Lam
Hypertension.2017; 70(6): 1273. CrossRef

Obesity and Metabolic Syndrome
Diabetes Prevention in Australia: 10 Years Results and Experience: James A. Dunbar; Diabetes Metab J. 2017;41(3):160-167. Published online February 2, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.3.160

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Clinical trials have demonstrated the efficacy of lifestyle modification for the prevention of type 2 diabetes mellitus but it was achieved at higher cost than can be sustained in routine health services. The first clinical trial to report was the Finnish Diabetes Prevention Study. This paper describes how Australia worked with Finnish colleagues to adapt the findings of that study to achieve a statewide diabetes prevention program. Small evaluative, effectiveness trials have been conducted in a number of countries to see if the results of the clinical trials can be replicated in routine health services. The Australian evaluative trial, Greater Green Triangle Diabetes Prevention Program is described in detail to demonstrate the ingredients for success in moving a program from one country to another. Few countries have managed to scale up from evaluative trials to statewide or national programs. The Australian experience is described in detail including lessons learned about what reduced the effectiveness, particularly the need for policy makers in government, people from the implementing organisation and researchers to work together from the start of the evaluative trial and throughout the first 5 years of a national program.

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Lucy E. Campbell, Sjaan R. Gomersall, Michael Tsiamis, Ana D. Goode, Genevieve N. Healy
Health Promotion Journal of Australia.2025;[Epub] CrossRef
Characteristics of participants in the first fully online National Diabetes Prevention Programme: A quantitative survey
Clair Haseldine, Gráinne O'Donoghue, Patricia M Kearney, Fiona Riordan, Margaret Humphreys, Liz Kirby, Sheena M. McHugh
HRB Open Research.2025; 6: 61. CrossRef
Clinically Practical and Affordable Lifestyle Modification to Prevent Diabetes Mellitus in Real Practice
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Characteristics of participants in the first fully online National Diabetes Prevention Programme: A quantitative survey
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HRB Open Research.2024; 6: 61. CrossRef
Lifestyle interventions for cardiometabolic health
Femke Rutters, Nicolette R. den Braver, Jeroen Lakerveld, Joreintje D. Mackenbach, Hidde P. van der Ploeg, Simon Griffin, Petra J. M. Elders, Joline W. J. Beulens
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Characteristics of participants in the first fully online National Diabetes Prevention Programme: A quantitative survey
Clair Haseldine, Gráinne O'Donoghue, Patricia M Kearney, Fiona Riordan, Margaret Humphreys, Liz Kirby, Sheena M. McHugh
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Qiqi You, Qingqing Jiang, Irakoze Shani, Yiling Lou, Shen Huang, Shiqi Wang, Shiyi Cao
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Helen Dallosso, Kamlesh Khunti, Laura J. Gray, Kerry Hulley, Mel Ghaly, Naina Patel, Joe Kai, Navneet Aujla, Melanie J. Davies, Tom Yates
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Britney McMullen, Kerith Duncanson, David Schmidt, Clare Collins, Lesley MacDonald-Wicks
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Characteristics of participants in the first fully online National Diabetes Prevention Programme: A quantitative survey
Clair Haseldine, Gráinne O'Donoghue, Patricia M Kearney, Fiona Riordan, Margaret Humphreys, Liz Kirby, Sheena M. McHugh
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Obesity and Metabolic Syndrome
Metabolic Surgery for Type 2 Diabetes Mellitus: Experience from Asia: Wei-Jei Lee, Lwin Aung; Diabetes Metab J. 2016;40(6):433-443. Published online December 2, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.433

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Type 2 diabetes mellitus (T2DM) is a current global health priority and Asia is the epicenter of this epidemic disease. Unlike in the west, where older population is most affected, the burden of diabetes in Asian countries is disproportionately high in young to middle-age adults. The incidence of diabetic nephropathy is alarmingly high in patients with early onset T2DM, especially in those with poor glycemic control. How to control this chronic and debilitating disease is currently a very important health issue in Asia. Bariatric surgery has proven successful in treating not just obesity but also T2DM in morbid obese patients (body mass index [BMI] >35 kg/m²). Gastrointestinal metabolic surgery recently has been proposed as a new treatment modality for obesity related T2DM for patients with BMI <35 kg/m². Many studies from Asia reported promising results of metabolic surgery to treat obese patients with T2DM which is not well controlled. It has been demonstrated that changes in gastrointestinal hormone secretion after gastrointestinal surgery would favor an early improvement of T2DM in Asians. New procedures have also been designed and proposed specifically for the treatment of diabetes in Asia. This article examines clinical trial data and accepted algorithms with a view toward elucidating the application of metabolic surgery for the treatment of T2DM in the Asia. We propose a systematic approach to surgical treatment, addressing current evidences, patient selection, procedure of choice, and timing and guideline for new procedures.

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Original Articles

Others
Effect of Atorvastatin on Growth Differentiation Factor-15 in Patients with Type 2 Diabetes Mellitus and Dyslipidemia: Ji Min Kim, Min Kyung Back, Hyon-Seung Yi, Kyong Hye Joung, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2016;40(1):70-78. Published online February 19, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.1.70

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Background

Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated.

Methods

In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels ≥100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (n=23) or 40 mg/day (n=27). The effect of atorvastatin on metabolic parameters, including lipid profiles and GDF-15 levels, at baseline and after 8 weeks of treatment were compared.

Results

The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6±874.8 to 1,451.0±770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6±801.0 to 1,341.4±855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (P=0.665 and P=0.745, respectively).

Conclusion

The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients.

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The relationship of Growth differentiation factor-15 with renal damage and dyslipidemia in non-albuminuric and albuminuric Type-2 Diabetes Mellitus
Hasan Esat Yücel, Bilal İlanbey
Medical Science and Discovery.2022; 9(6): 334. CrossRef
Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis
Alexander Hodkinson, Dialechti Tsimpida, Evangelos Kontopantelis, Martin K Rutter, Mamas A Mamas, Maria Panagioti
BMJ.2022; 376: e067731. CrossRef
The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker
Boel De Paepe
International Journal of Molecular Sciences.2022; 23(21): 13180. CrossRef
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Hannah Kaiser, Xing Wang, Amanda Kvist-Hansen, Martin Krakauer, Peter Michael Gørtz, Benjamin D. McCauley, Lone Skov, Christine Becker, Peter Riis Hansen
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Kathrin Ackermann, Gabriel A. Bonaterra, Ralf Kinscherf, Anja Schwarz
Atherosclerosis.2019; 281: 128. CrossRef

Obesity and Metabolic Syndrome
Increased Risk of Progression of Coronary Artery Calcification in Male Subjects with High Baseline Waist-to-Height Ratio: The Kangbuk Samsung Health Study: Hyung-Geun Oh, Shriram Nallamshetty, Eun-Jung Rhee; Diabetes Metab J. 2016;40(1):54-61. Published online February 19, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.1.54

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Background

The waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of baseline WHtR and progression of coronary artery calcification (CAC) over 4 years of follow-up in apparently healthy Korean men.

Methods

A total of 1,048 male participants (mean age, 40.9 years) in a health-screening program in Kangbuk Samsung Hospital, Seoul, Korea who repeated a medical check-up in 2010 and 2014 were recruited. Baseline WHtR was calculated using the value for the waist in 2010 divided by the value for height in 2010. The CAC score (CACS) of each subject was measured by multi-detector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years greater than 0.

Results

During the follow-up period, progression of CAC occurred in 278 subjects (26.5%). The subjects with CAC progression had slightly higher but significant baseline WHtR compared to those who did not show CAC progression (0.51±0.04 vs. 0.50±0.04, P<0.01). The proportion of subjects with CAC progression significantly increased as the baseline WHtR increased from the 1st quartile to 4th quartile groups (18.3%, 18.7%, 28.8%, and 34.2%; P<0.01). The risk for CAC progression was elevated with an odds ratio of 1.602 in the 4th quartile group of baseline WHtR even after adjustment for confounding variables (95% confidence interval, 1.040 to 2.466).

Conclusion

Increased baseline WHtR was associated with increased risk for CAC progression. WHtR might be a useful screening tool to identify individuals at high risk for subclinical atherosclerosis.

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Mahmood Shaker Khazaal, Farqad Bader Hamdan, Qasim Sharhan Al-Mayah
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Audai A Hayajneh, Islam M Alhusban, Mohammad Rababa, Sami Al-Rawashdeh, Shatha Al-Sabbah, Dania Bani-Hamad
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Review

Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk: Leigang Jin, Zhuofeng Lin, Aimin Xu; Diabetes Metab J. 2016;40(1):22-31. Published online January 29, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.1.22

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Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.

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Original Article

Complications
Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis: Jaechan Leem, Eun Hee Koh, Jung Eun Jang, Chang-Yun Woo, Jin Sun Oh, Min Jung Lee, Joon-Won Kang, Tae-Hwan Lim, Chang Hee Jung, Woo Je Lee, Joong-Yeol Park, Ki-Up Lee; Diabetes Metab J. 2015;39(5):414-423. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.414

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Abstract PDF PubReader ePub

Background

The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD.

Methods

We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery.

Results

Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028).

Conclusion

Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.

Citations

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