Diabetes & Metabolism Journal

Original Articles

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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Abstract PDF Supplementary Material PubReader ePub: Background
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.

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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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.

Citations

Citations to this article as recorded by

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

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