Diabetes & Metabolism Journal

Original Articles

Complications
Cardiorespiratory Fitness and Risk of Microvascular Complications in Patients with Type 2 Diabetes Mellitus: Anning Xu, Haofeng Zhou, Chaofan Wang, Qian He, Ping Wu, Wenjing Wu, Hongjiang Wu, Alice P.S. Kong, Huanyi Cao, Haixia Guan, Yunjiu Cheng; Received November 5, 2025 Accepted February 10, 2026 Published online May 18, 2026; DOI: https://doi.org/10.4093/dmj.2025.1109 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
To investigate the association between cardiorespiratory fitness (CRF) and the risk of incident microvascular complications in patients with type 2 diabetes mellitus (T2DM), and to assess the effect of genetic risk and potential mediation by circulating biomarkers.
Methods
This prospective analysis included 3,102 adults with T2DM from the UK Biobank. CRF was estimated as maximal oxygen uptake using a submaximal cycle test and categorized as low, moderate, or high. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident diabetic nephropathy, retinopathy, and neuropathy. Interactions with a polygenic risk score and mediating roles of biomarkers were evaluated.
Results
Over a median 12.47-year follow-up, 331 nephropathy, 268 retinopathy, and 88 neuropathy cases were recorded. Compared to low CRF, moderate and high CRF were associated with 22% (HR, 0.78; 95% confidence interval [CI], 0.61 to 0.99) and 45% (HR, 0.55; 95% CI, 0.36 to 0.85) lower risks of nephropathy, respectively. Each 1-metabolic equivalent of task increment in CRF was linked to 11% lower nephropathy risk. No significant associations were found for retinopathy or neuropathy. Genetic predisposition did not modify the association between CRF and diabetic nephropathy. Triglycerides and white blood cell count accounted for 7.46% and 12.88% of the association, respectively.
Conclusion
Higher CRF is independently associated with lower risk of diabetic nephropathy in T2DM, and genetic risk does not alter this relationship. The association was partially mediated by triglycerides and white blood cell count. Assessing CRF may improve risk stratification and prevention of diabetic kidney disease.

Metabolic Risk/Epidemiology
Healthy Lifestyle and the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Large Prospective Cohort Study: Qing Chang, Yixiao Zhang, Tingjing Zhang, Zuyun Liu, Limin Cao, Qing Zhang, Li Liu, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Yang Ding, Yuhong Zhao, Kaijun Niu, Yang Xia; Diabetes Metab J. 2024;48(5):971-982. Published online March 19, 2024; DOI: https://doi.org/10.4093/dmj.2023.0133

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Background
The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD.
Methods
A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors.
Results
The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle.
Conclusion
Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Citations

Citations to this article as recorded by

The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease
Ioannis Tsomidis, Angeliki Tsakou, Argyro Voumvouraki, Elias Kouroumalis
Biomedicines.2026; 14(1): 151. CrossRef
Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review
Aleksandra Klisic, Ratko Tomašević, Slavko Djuraskovic, Filiz Mercantepe, Ana Ninic
Archives of Medical Science.2026;[Epub] CrossRef
Impact of healthy lifestyles on the risk of metabolic dysfunction‐associated steatotic liver disease among adults with comorbid hypertension and diabetes: Novel insight from a largely middle‐aged and elderly cohort in South China
Jun‐Yan Xi, Yi‐Jing Wang, Xiao‐Heng Li, Nuo‐Min Sun, Rui‐Qi Ming, Hua‐Ling Yan, Huan‐Le Cai, Jian‐Jun Bai, Yi‐Ning Xiang, Jing Gu, Xiao Lin, Gang Liu, Yuan‐Tao Hao
Diabetes, Obesity and Metabolism.2025; 27(5): 2800. CrossRef
Cholesteryl ester transfer protein gene variants and metabolic dysfunction-associated steatotic liver disease: genetic associations with steatosis in obese and lean individuals
Asmaa AbdelFattah, Mahmoud Kattab, Hosny Abdel Ghany, Lamiaa Aly, Ahmed Mady, Aly Hamdi, Riham Soliman, Gamal Shiha, Nada El-Domiaty
Egyptian Liver Journal.2025;[Epub] CrossRef
Research trends on the quality of life in patients with metabolic dysfunction-associated fatty liver diseases: a scientific metrology study
Can Huang, Meng Chen, Yanfang Sun, Lin Zhang, Wei Liu
Frontiers in Nutrition.2025;[Epub] CrossRef
The relationship between tobacco and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis of observational studies
Jianxiang Jin, Yuping Zhang, Yiping Huang
Frontiers in Medicine.2025;[Epub] CrossRef
Enhancing MAFLD Care: Efficacy of a Multidisciplinary Community Intervention on Self-Management and Hepatic Outcomes
Huan-Jing Cai, Hai-Lun Liang, Lei-Yu Shi, Yi-Hui Rong, Jing Li, Yan Zhang, Rui-Fang Ma
INQUIRY: The Journal of Health Care Organization, Provision, and Financing.2025;[Epub] CrossRef
Mechanistic investigation of DDT/DDE in MASLD/MASH pathogenesis: An integrated network toxicology and transcriptomics approach
Yicheng Jiang, Yuancheng Shao, Jiaming Xue, Zhigang Chen, Qi Liu, Shuai Chen, Xihan Gu, Shufan Zhang, Liming Tang
Ecotoxicology and Environmental Safety.2025; 307: 119390. CrossRef
Multiorgan crosstalk in MASLD/MASH: from hepatic pathogenesis to systemic complications
Wenhua Bai, Zheng Zhu
Frontiers in Endocrinology.2025;[Epub] CrossRef
Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease
Tianzhu Chen, Xiang Qin, Jianping Jiang, Beihui He
Frontiers in Nutrition.2024;[Epub] CrossRef
Sex differences in pathogenesis and treatment of dyslipidemia in patients with type 2 diabetes and steatotic liver disease
Tatjana Ábel, Béla Benczúr, Éva Csajbókné Csobod
Frontiers in Medicine.2024;[Epub] CrossRef
Associations of traditional healthy lifestyle and sleep quality with metabolic dysfunction-associated fatty liver disease: two population-based studies
Jialu Yang, Qi Zhang, Wanying Zhao, Bingqi Ye, Siqi Li, Zhuoyu Zhang, Jingmeng Ju, Jialin He, Min Xia, Tiantian Xiong, Yan Liu
Nutrition & Diabetes.2024;[Epub] CrossRef

Metabolic Risk/Epidemiology
Prediabetes Progression and Regression on Objectively- Measured Physical Function: A Prospective Cohort Study: Shanhu Qiu, Yiming Zhu, Bo Xie, Wenji Chen, Duolao Wang, Xue Cai, Zilin Sun, Tongzhi Wu; Diabetes Metab J. 2023;47(6):859-868. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0377

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Background
Prediabetes leads to declines in physical function in older adults, but the impact of prediabetes progression or regression on physical function is unknown. This study assessed this longitudinal association, with physical function objectivelymeasured by grip strength, walking speed, and standing balance, based on the Health and Retirement Study enrolling United States adults aged >50 years.
Methods
Participants with prediabetes were followed-up for 4-year to ascertain prediabetes status alteration (maintained, regressed, or progressed), and another 4-year to assess their impacts on physical function. Weak grip strength was defined as <26 kg for men and <16 kg for women, slow walking speed was as <0.8 m/sec, and poor standing balance was as an uncompleted fulltandem standing testing. Logistic and linear regression analyses were performed.
Results
Of the included 1,511 participants with prediabetes, 700 maintained as prediabetes, 306 progressed to diabetes, and 505 regressed to normoglycemia over 4 years. Grip strength and walking speed were declined from baseline during the 4-year followup, regardless of prediabetes status alteration. Compared with prediabetes maintenance, prediabetes progression increased the odds of developing weak grip strength by 89% (95% confidence interval [CI], 0.04 to 2.44) and exhibited larger declines in grip strength by 0.85 kg (95% CI, –1.65 to –0.04). However, prediabetes progression was not related to impairments in walking speed or standing balance. Prediabetes regression also did not affect any measures of physical function.
Conclusion
Prediabetes progression accelerates grip strength decline in aging population, while prediabetes regression may not prevent physical function decline due to aging.

Citations

Citations to this article as recorded by

Changes in impaired physical function in older adults and the influences of physical activity: a population-based cohort study
Shanhu Qiu, Bo Xie, Zilin Sun, Xue Cai, Tongzhi Wu
BMC Geriatrics.2026;[Epub] CrossRef
Development of a scoring system for vitality capacity assessment in older adults: a population-based study
Xue Cai, Cuirong Xu, Zhiju Gu, Tongzhi Wu, Shanhu Qiu
European Geriatric Medicine.2025; 17(2): 1065. CrossRef
Cluster-based subgroups of prediabetes and its association with prediabetes progression and regression: a prospective cohort study
Yan Liu, Yu Liu, Min Zhang, Xinchen Wang, Xiaoying Zhou, Haijian Guo, Bei Wang, Duolao Wang, Zilin Sun, Shanhu Qiu
Acta Diabetologica.2024; 62(7): 1139. CrossRef

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