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; Diabetes Metab J. 2026;50(4):770-784. Published online March 25, 2026; DOI: https://doi.org/10.4093/dmj.2024.0814

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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 group or a resting group. Serum fibroblast growth factor 21 (FGF21) levels and untargeted metabolomic profiles were assessed at multiple time points before and after exercise. Interstitial glucose levels were monitored using continuous glucose monitoring system. FGF21 knockout mice and wild-type littermates fed a high-fat diet underwent a 3-week exercise intervention and received FGF21 supplementation.
Results
Individuals exhibiting delayed glycemic improvement (responders) displayed a significantly stronger FGF21 response than 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 the role of FGF21 in modulating delayed glycemic improvement through regulation of lipid metabolism. In vivo FGF21 knockout and rescue experiments demonstrated that FGF21 is necessary for these metabolic shifts and the associated improvements in glucose tolerance and insulin sensitivity.
Conclusion
This study suggests that the baseline metabolome is associated with the magnitude of the post-exercise FGF21 response, which influences delayed glycemic improvement 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

Genetics
Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes: Siqian Gong, Hong Lian, Yating Li, Xiaoling Cai, Wei Liu, Yingying Luo, Meng Li, Si-min Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Qian Ren, Xiuying Zhang, Jing Chen, Jing Wu, Xianghai Zhou, Xirui Wang, Xueyao Han, Linong Ji; Diabetes Metab J. 2025;49(2):321-330. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0159

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Abstract PDF Supplementary Material PubReader ePub

Background
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Citations

Citations to this article as recorded by

Transient neonatal diabetes mellitus as an early diagnostic clue to HNF1B-related disease – two case reports and a literature review
Marcin Kołbuc, Paweł Bednarek, Rafał Motyka, Tomasz Jarmoliński, Marzena Michalak-Kloc, Bodo B. Beck, Małgorzata Urbańska-Kosińska, Marcin Zaniew
Molecular and Cellular Pediatrics.2026;[Epub] CrossRef
Diabetes associated with HNF1B: beyond Occam’s razor—A case report
Carolina Sager-La Ganga, Clara Solà, Karen Castillo, Carme Figueredo, Ignacio Conget
Acta Diabetologica.2025; 62(8): 1347. CrossRef

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