Increased serum/plasma fibroblast growth factor 21 in type 2 diabetes mellitus: A systematic review and meta-analysis
Abstract
Abstract Objectives Fibroblast growth factor-21 (FGF-21) plays an important role in glucose and lipid metabolism. This study aims to systemically review the evidence regarding the relationship between the FGF-21 levels and type 2 diabetes mellitus (T2DM), as well as the related influential factors. Methods Research related to plasma/serum FGF-21 levels in patients with T2DM and healthy controls were searched in PubMed, EMBASE and The Cochrane Library databases (up to 31 March 2017). Pooled standard mean difference (SMD) with 95% CI was calculated by fixed-effect or random-effect model analysis. Heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot and Egger’s linear regression test. Results In total, 317 articles were obtained after searching databases, and 11 studies with 866 patients with T2DM and 629 controls were finally included. Meta-analysis revealed that, compared with the control group, the T2DM group had a significantly higher plasma/serum FGF-21 level (p < 0.001), with the SMD of 1.34% and 95% CI (0.70 to 1.98). Meta-regression analysis and subgroup analyses suggested that body mass index (BMI), triglycerides (TG) and total cholesterol (TC) were likely related to the observed FGF-21 differences between two groups. Conclusions Overall, our study suggests that patients with T2DM have significantly higher plasma/serum FGF-21 levels, and the FGF-21 levels were influenced by BMI, TC and TG.
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In obesity and type 2 diabetes, FGF21 resistance is common: circulating levels are elevated but receptor signaling is impaired.
“In obesity and type 2 diabetes, FGF21 resistance is common: circulating levels are elevated but receptor signaling is impaired, as documented in human studies [51,52,53].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [51]
Myokine resistance-observed for irisin and FGF21 in obese and diabetic states-complicates interpretation, as elevated circulating levels may reflect target tissue insensitivity rather than enhanced function.
“Third, the phenomenon of myokine resistance—observed for irisin [42,43] and FGF21 [51,52] in obese and diabetic states—complicates interpretation, as elevated circulating levels may reflect target tissue insensitivity rather than enhanced function.”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [51]
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- Authors
- Wang, Y.-S., Ye, J., Cao, Y.-H., Zhang, R., Liu, Y., Zhang, S.-W., Dai, W., & Zhang, Q.
- Affiliations
- First Affiliated Hospital of Anhui Medical University (CN)
- Department of Endocrinology, The Second People’s Hospital of Hefei , Hefei , China
- Corresponding author
- Dai, Wu
- Zhang, Qiu
- Venue
- Postgraduate Medical Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-03-01
- Volume
- 95
- Issue
- 1121
- Pages
- 134-139
- ISSN
- 0032-5473 (ISSN-L)
- 1469-0756
- OpenAlex
- W2924708717
- Cited by
- 32
- References
- 33
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 1
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Postgraduate Medical Journal (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Science & Technology Commission of Anhui Province of China (1604a0802099)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- FGF21, type 2 diabetes, serum biomarkers, body mass index, triglycerides, total cholesterol, lipid metabolism, glucose metabolism
- MeSH terms
- Diabetes Mellitus, Type 2, Fibroblast Growth Factors, Humans, Biomarkers
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