Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease: Inseon Hwang, Jung Eun Nam, Wonsuk Choi, Won Gun Choi, Eunji Lee, Hyeongseok Kim, Young-Ah Moon, Jun Yong Park, Hail Kim; Diabetes Metab J. 2025;49(4):798-811. Published online February 5, 2025; DOI: https://doi.org/10.4093/dmj.2024.0215; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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Background
Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine neurotransmitter that has various functions in central and peripheral tissues. While 5-HT is known to regulate various biological processes in liver, direct role of 5-HT and its receptors, especially 5-HT receptor 2A (HTR2A) and HTR2B, in development and progression of alcoholic liver disease (ALD) in vivo is not well understood.
Methods
Blood 5-HT level was measured from both human ALD patients and ethanol (EtOH) diet-fed mouse models. Gut-specific tryptophan hydroxylase 1 (Tph1) knockout mice, liver-specific Htr2a knockout mice, and liver-specific Htr2b knockout mice were fed with EtOH diet. Then we evaluated liver damage, hepatic steatosis, endoplasmic reticulum (ER) stress, and inflammation.
Results
Blood 5-HT concentrations are increased in both humans and mice with ALD. Both gut-specific Tph1 knockout and liver- specific Htr2a knockout mice are resistant to steatosis by down-regulating lipogenic pathways in liver of chronic EtOH diet-fed mice. Moreover, genetic inhibition of both gut-derived serotonin (GDS) synthesis and hepatic HTR2A signaling prevents ER stress in liver of chronic EtOH diet-fed mice. Additionally, we found that ablation of HTR2A signaling protects against disease progression by attenuating liver injury and inflammation in chronic plus binge EtOH diet-fed mice. Also, inhibiting HTR2A signaling ameliorates alcohol-induced liver injury and ER stress in an acute EtOH diet-fed mice model.
Conclusion
GDS directly regulates lipogenesis and ER stress via signaling through hepatic HTR2A in the context of ALD. Inhibiting HTR2A signaling protects against alcohol-induced steatosis, liver injury and disease progression in various ALD mouse models and may also provide a novel therapeutic strategy for ALD.

Citations

Citations to this article as recorded by

Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions
Yuting Zhu, Yuqing Jia, Enming Zhang
Frontiers in Pharmacology.2025;[Epub] CrossRef

Others
Contributions of Hepatic Insulin Resistance and Islet β-Cell Dysfunction to the Blood Glucose Spectrum in Newly Diagnosed Type 2 Diabetes Mellitus: Mengge Yang, Ying Wei, Jia Liu, Ying Wang, Guang Wang; Diabetes Metab J. 2025;49(4):883-892. Published online February 13, 2025; DOI: https://doi.org/10.4093/dmj.2024.0537; Funded: National Key Research and Development Program of China, Beijing Hospital Authority, National Natural Science Foundation of China

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Background
Our previous studies have investigated the role of hepatic insulin resistance (hepatic IR) and islet β-cell function in the pathogenesis of diabetes. This study aimed to explore the contributions of hepatic IR and islet β-cell dysfunction to the blood glucose spectrum in patients with newly diagnosed type 2 diabetes mellitus.
Methods
Hepatic IR was assessed by the hepatic insulin resistance index (HIRI). Islet β-cell function was assessed by insulin secretion- sensitivity index-2 (ISSI2). The associations between blood glucose spectrum and hepatic IR and ISSI2 were analyzed.
Results
A total of 707 patients with new-onset diabetes were included. The fasting blood glucose (FBG) and 30 minutes postload blood glucose elevated with rising HIRI (both P for trend <0.001). The FBG, 30 minutes, 2 hours, and 3 hours post-load blood glucose elevated with decreasing ISSI2 quartiles (all P for trend <0.001). There was a negative correlation between ISSI2 and HIRI after adjusting blood glucose levels (r=–0.199, P<0.001).
Conclusion
Hepatic IR mainly contributed to FBG and early-phase postprandial plasma glucose, whereas β-cell dysfunction contributed to fasting and postprandial plasma glucose at each phase.

Citations

Citations to this article as recorded by

GLDC attenuates liver ischemia-reperfusion injury by inhibiting macrophage recruitment and activation via PTBP1/P2RY6
Zhitao Li, Li Jin, Yuan Fang, Siming Qu, Bo Yuan, Kai Gan, Hanfei Huang
Cellular Signalling.2025; 135: 111976. CrossRef

Metabolic Risk/Epidemiology
The Impact of Obesity on the Association between Parity and Risk of Type 2 Diabetes Mellitus: Yuki Gen, Kyuho Kim, Joonyub Lee, Junyoung Jung, Sang-Hyuk Jung, Hong-Hee Won, Dokyoon Kim, Yun-Sung Jo, Yu-Bae Ahn, Seung-Hyun Ko, Jae-Seung Yun; Diabetes Metab J. 2025;49(4):837-847. Published online February 14, 2025; DOI: https://doi.org/10.4093/dmj.2024.0536; Funded: National Research Foundation of Korea

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Abstract PDF Supplementary Material PubReader ePub: Background
Most studies focus solely on the relationship between parity and type 2 diabetes mellitus (T2DM) risk, providing limited insights into other contributing or protective factors. This study aims to explore the complex relationship between parity and T2DM risk, considering additional factors such as obesity, race, and body composition.
Methods
This prospective cohort study used data from 242,159 women aged 40 to 69 from the UK Biobank, none of whom had T2DM at baseline. Multivariable Cox proportional hazard models were applied to assess the association between parity and T2DM. Subgroup analyses were performed based on body mass index (BMI), waist circumference (WC), and race.
Results
The hazard ratio for T2DM per additional child was 1.16 (95% confidence interval, 1.13 to 1.16). Subgroup analysis revealed that Asian women and those with obesity or abdominal obesity had a higher risk of T2DM associated with multiparity. No increased risk was observed in women with normal BMI or WC. Mediation analysis showed that WC and BMI significantly mediated the parity-T2DM relationship, accounting for 49% and 38% of the effect, respectively.
Conclusion
There is a clear positive association between multiparity and T2DM risk, particularly in Asian women and those with obesity. Maintaining normal BMI and WC appears to mitigate this risk, highlighting the importance of weight management for women at higher parity levels. These findings offer crucial insights for public health interventions aimed at reducing T2DM risk among women.

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; Funded: National Research Foundation of Korea, Ministry of Science and ICT, Korea Health Industry Development Institute, Ministry of Health and Welfare

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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.

Citations

Citations to this article as recorded by

Role of Macrophage-Derived Progranulin in Energy and Glucose Metabolism
Do Kyeong Song
Diabetes & Metabolism Journal.2025; 49(4): 580. 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; Funded: Nanchang University, Postgraduate Innovation Special Fund of Jiangxi Province

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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.

Citations

Citations to this article as recorded by

Frailty and incident diabetes among middle-aged and older adults: Evidence from a large prospective cohort in China
Yingzhen Gu, Xiaorong Han, Jinxing Liu, Yifan Li, Wei Zhang, Naqiang Lv, Aimin Dang
Nutrition, Metabolism and Cardiovascular Diseases.2025; : 104114. CrossRef
Addressing Inequities in Early‐Onset Diabetic Kidney Failure in Australia: A Response to Ellis et al.
Gokhan Koker
Nephrology.2025;[Epub] CrossRef

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; Funded: National Key Research and Development Program of China , Excellent Young Scientists Fund of NSFC, General Fund of NSFC, Major Program of NSFC, Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Municipal Key Clinical Specialty, Shanghai Research Center for Endocrine and Metabolic Diseases, National Natural Science Foundation of China, Shanghai Pujiang Program, Exploration Fund Grant of Shanghai Sixth People’s Hospital

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Abstract PDF Supplementary Material PubReader ePub: 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.

Lifestyle and Behavioral Interventions
Association between Healthy Lifestyle Factors and Metabolic Syndrome Risk: A Prospective Analysis of the Korean Genome and Epidemiology Study: Jialei Fu, Sangah Shin; Diabetes Metab J. 2025;49(4):873-882. Published online March 26, 2025; DOI: https://doi.org/10.4093/dmj.2024.0427; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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To investigate the association of adherence to five modifiable lifestyle factors (limiting alcohol, physical activity, limiting smoking, favorable diet quality, and adequate sleep) with metabolic syndrome (MetS) risk in Korean adults.
Methods
Health Examinees Study data were used, and 41,368 participants aged 40 to 69 years were included. Cox proportional hazards regression analyses assessed the associations of individual and combined healthy lifestyle factors (32 and 16 lifestyle profiles in men and women.
Results
During a median 4.2-year follow-up, 6,213 participants were newly diagnosed with MetS. Adherence to more healthy lifestyle factors (4–5 vs. 0–1) could lower MetS risk by 28% and 12% in men and women (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63 to 0.83 in men; HR, 0.88; 95% CI, 0.78 to 0.99 in women). Each additional healthy lifestyle could reduce the risk of MetS by 10% and 6% in men and women. The pooled analysis yielded similar results based on similar numbers of healthy lifestyle factors, the risk of MetS decreased as the number of healthy lifestyle factors increased.
Conclusion
Adherence to more healthy lifestyle factors was inversely associated with MetS risk. These findings highlight the importance of limiting drinking in managing MetS. Future research should consider the synergistic effects of emerging lifestyle factors, such as sleep duration, on chronic disease development, while focusing on the effects of traditional lifestyle factors.

Type 1 Diabetes
Global Burden of Type 1 Diabetes Mellitus Related Chronic Kidney Disease among Adolescents and Young Adults, and Projections to 2035: Results from the Global Burden of Disease Study 2021: Xiaoli Qu, Chongbin Liu, Lin Sun, Zhifeng Sheng; Diabetes Metab J. 2025;49(4):812-825. Published online March 10, 2025; DOI: https://doi.org/10.4093/dmj.2024.0544; Funded: National Natural Science Foundation of China, Hunan Provincial Natural Science Foundation of China, Hunan Provincial Clinical Medicine Research Center for Intelligent Management of Chronic Disease, Central South University, Hunan Provincial Health Commission, Bethune Charitable Foundation, Central Subsidy for Prevention and Control of Major Infectious Diseases, HANS CARING Inc.

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Abstract PDF Supplementary Material PubReader ePub: Background
Type 1 diabetes mellitus related chronic kidney disease (T1DM-CKD) presents a global health challenge, with unclear trends and patterns among adolescents and young adults. This study analyzed the burden and risk factors of T1DM-CKD in individuals aged 15 to 39 from 1990 to 2021 and predicted future trends.
Methods
Using data from the Global Burden of Disease (GBD) study 2021, we analyzed the prevalence, incidence, mortality, disability-adjusted life years (DALYs), and average annual percentage change (AAPC) of T1DM-CKD among youth across gender, sociodemographic index (SDI) areas, and data from 21 regions and 204 countries and territories. Risk factors were assessed and future trends were projected.
Results
Between 1990 and 2021, the global prevalence of T1DM-CKD aged 15 to 39 increased by 107.5% to 3.32 million, with an age-standardized prevalence rate (ASPR) of 111.44 per 100,000 (AAPC 1.33%). Incidence rose by 165.4% to 14,200, with an agestandardized incidence rate of 0.48 per 100,000 (AAPC 2.19%). However, age-standardized mortality rate (0.50 per 100,000, AAPC –0.87%) and age-standardized DALYs rate (30.61 per 100,000, AAPC –0.83%) decreased. ASPR increased across all SDI regions, especially in high-SDI countries. High fasting glucose remained the major risk factor influencing DALYs. By 2035, T1DM-CKD prevalence was projected to decrease to 2.86 million (ASPR 89.67 per 100,000).
Conclusion
The research revealed a global increase in T1DM-CKD among youth, with a shift towards younger onset and significant variations based on gender and location, emphasizing the importance of early prevention and management strategies for this demographic.

Complications
Risk of End-Stage Kidney Disease in Individuals with Diabetes Living Alone: A Large-Scale Population-Based Study: Kyunghun Sung, Jae-Seung Yun, Bongseong Kim, Hun-Sung Kim, Jae-Hyoung Cho, Yong-Moon Mark Park, Kyungdo Han, Seung-Hwan Lee; Diabetes Metab J. 2025;49(4):862-872. Published online April 5, 2025; DOI: https://doi.org/10.4093/dmj.2024.0578; Funded: National Research Foundation of Korea, National Center for Advancing Translational Sciences of the National Institutes of Health

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Abstract PDF Supplementary Material PubReader ePub: Background
Previous research has linked solitary living to various adverse health outcomes, but its association with diabetic complications among individuals with type 2 diabetes mellitus (T2DM) remains underexplored. We examined the risk of endstage kidney disease (ESKD) in individuals with diabetes living alone (IDLA).
Methods
This population-based cohort study used the National Health Information Database of Korea, which included 2,432,613 adults with T2DM. Household status was determined based on the number of registered family members. IDLA was defined as continuously living alone for 5 years or more. A multivariable Cox proportional hazards model was used to evaluate the association between living alone and the risk of developing ESKD.
Results
During a median follow-up of 6.0 years, 26,691 participants developed ESKD, with a higher incidence observed in the IDLA group than in the non-IDLA group. After adjusting for confounding variables, the hazard ratio for ESKD in the IDLA group was 1.10 (95% confidence interval, 1.06 to 1.14). The risk of ESKD was particularly elevated in younger individuals, those without underlying chronic kidney disease, with longer durations of living alone, and with low household income. Adherence to favorable lifestyle behaviors (no smoking, no alcohol consumption, and engaging in regular exercise) was associated with a significantly lower risk of ESKD, with a more pronounced effect in the IDLA group.
Conclusion
Living alone was associated with a higher risk of ESKD in individuals with T2DM. Tailored medical interventions and social support for IDLA are crucial for the prevention of diabetic complications.

Review

Pharmacotherapy
Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning: Jung A Kim, Hye Jin Yoo; Diabetes Metab J. 2025;49(4):525-541. Published online July 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0242; Funded: National Research Foundation of Korea, Ministry of Education

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Abstract PDF PubReader ePub: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated considerable efficacy in the treatment of diabetes and obesity, it is essential to recognize that their use is associated with certain intrinsic risks that must not be disregarded. The incidence of adverse effects, particularly gastrointestinal complications, psychiatric disorders, and ocular problems, highlights the critical need for thorough patient assessment and continuous monitoring to ensure both the safety and effectiveness of treatment. Despite the possibility of adverse events, GLP-1 RAs continue to represent a crucial therapeutic modality for metabolic disturbances. This highlights the significance of ongoing research initiatives aimed at optimizing their safe utilization and refining current treatment protocols to improve patient outcomes. This review summarizes updated research findings regarding the adverse effects of GLP-1 RAs, their mechanisms of action, and guidelines for clinical application.

Original Articles

Guideline/Statement/Fact Sheet
2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association: Shinae Kang, Seon Mee Kang, Jong Han Choi, Seung-Hyun Ko, Bo Kyung Koo, Hyuk-Sang Kwon, Mi Kyung Kim, Sang Yong Kim, Soo-Kyung Kim, Young-eun Kim, Eun Sook Kim, Jae Hyeon Kim, Chong Hwa Kim, Ji Min Kim, Hae Jin Kim, Min Kyong Moon, Sun Joon Moon, Jun Sung Moon, Joon Ho Moon, Se Hee Min, Jung Hwan Park, Jaehyun Bae, Keeho Song, Ji Yoon Ahn, Jae-Seung Yun, Woo Je Lee, You-Bin Lee, Suk Chon, Eonju Jeon, Sang-Man Jin, Eugene Han, You-Cheol Hwang, Jae Hyun Bae, YoonJu Song, Jeong Hyun Lim, Jae Won Cho, Ji Yeon Choi, Yong Hee Hong, Jieun Lee, Sung Eun Kim, Ji Yun Noh, Bong-Soo Cha, Byung-Wan Lee; Diabetes Metab J. 2025;49(4):582-783. Published online July 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0469; Funded: Korean Diabetes Association

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Cardiovascular Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study: Honglin Sun, Zhenyu Wu, Guang Wang, Jia Liu; Diabetes Metab J. 2025;49(3):448-461. Published online January 20, 2025; DOI: https://doi.org/10.4093/dmj.2024.0100; Funded: National Key Research and Development Program of China , National Natural Science Foundation of China, Capital Medical University , Beijing Natural Science Foundation

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

Citations

Citations to this article as recorded by

Monitoring Sarcopenia With Incretin Receptor Activator Treatment
Zachary T. Bloomgarden
Journal of Diabetes.2025;[Epub] CrossRef

Basic and Translational Research
Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A: Junmei Wang, Shuai Huang, Li Zhang, Yixian He, Xian Shao, A-Shan-Jiang A-Ni-Wan, Yan Kong, Xuying Meng, Pei Yu, Saijun Zhou; Diabetes Metab J. 2025;49(3):421-435. Published online January 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0398; Funded: National Natural Science Foundation of China, China Endocrine Metabolism Talent Research Fund, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin Key Laboratory of Metabolic Diseases, Bethune Charitable Foundation, Hubei Chen Xiaoping Science and Technology Development Fund, Tianjin Science and Technology Plan Project, Public Health Science and Technology Major Special Project, Tianjin Education Commission, Nature Science Foundation of Tianjin, China, Tianjin Key Medical Discipline (Specialty) Construction Project

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Abstract PDF Supplementary Material PubReader ePub: Background
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Basic and Translational Research
Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization: Li Jiang, Jie Jian, Xulin Sai, Xiai Wu; Diabetes Metab J. 2025;49(3):407-420. Published online January 24, 2025; DOI: https://doi.org/10.4093/dmj.2024.0233; Funded: National High Level Hospital Clinical Research Funding, National Natural Science Foundation of China

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.
Methods
Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.
Results
The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.
Conclusion
VCAN showed the prospects into DKD pathology and clinical indicator.

Brief Report

Others
Alpha-Tocopherol-Loaded Liposomes Reduce High Glucose Induced Oxidative Stress in Schwann Cells: A Proof of Concept Study: Jee-In Heo, Mi Jeong Kim, Daehyun Kim, Jimin Seo, Joon Ho Moon, Sung Hee Choi, Hak Jong Lee, Tae Jung Oh; Diabetes Metab J. 2025;49(3):507-512. Published online February 5, 2025; DOI: https://doi.org/10.4093/dmj.2024.0489; Funded: Korean Diabetes Association and Daewoong Foundation, National Research Foundation of Korea, Ministry of Science and ICT

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Abstract PDF Supplementary Material PubReader ePub: Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

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