Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis
Open accessAbstract
Background: Gestational diabetes mellitus (GDM) is a prevalent condition where diabetes is diagnosed during pregnancy, affecting both maternal and fetal outcomes. Retinol-binding protein 4 (RBP4) is a circulating adipokine which belongs to the lipocalin family and acts as a specific carrier protein that delivers retinol (vitamin A) from the liver to the peripheral tissues. Growing data indicate that circulating RBP4 levels may positively correlate with GDM. Thus, this systematic review and meta-analysis aimed to investigate the potential relationship between circulating RBP4 levels and GDM when measured at various stages of pregnancy. Methods: MEDLINE, CINAHL, EMCARE, EMBASE, Scopus, and Web of Science databases were searched to identify studies comparing pregnant women with and without GDM, whose circulating RBP4 levels were measured in at least one pregnancy trimester. Findings were reported using standardized mean difference (SMD) and random-effects models were used to account for variability among studies. Furthermore, the risk of bias was assessed using the RoBANS tool. Results: Out of the 34 studies identified, 32 were included in the meta-analysis (seven with circulating RBP4 levels measured in the first trimester, 19 at 24–28 weeks, and 14 at >28 weeks of pregnancy). RBP4 levels were statistically higher in the GDM group than in controls when measured during all these pregnancy stages, with the noted RBP4 SMD being 0.322 in the first trimester (95% CI: 0.126–0.517; p < 0.001; 946 GDM cases vs. 1701 non-GDM controls); 0.628 at 24–28 weeks of gestation (95% CI: 0.290–0.966; p < 0.001; 1776 GDM cases vs. 1942 controls); and 0.875 at >28 weeks of gestation (95% CI: 0.252–1.498; p = 0.006; 870 GDM cases vs. 1942 non-GDM controls). Significant study heterogeneity was noted for all three pregnancy timepoints. Conclusion: The present findings indicate consistently higher circulating RBP4 levels in GDM cases compared to non-GDM controls, suggesting the potential relevance of RBP4 as a biomarker for GDM. However, the documented substantial study heterogeneity, alongside imprecision in effect estimates, underscores the need for further research and standardization of measurement methods to elucidate whether RBP4 can be utilized in clinical practice as a potential GDM biomarker. Systematic review registration: PROSPERO (CRD42022340097: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340097).
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A recent meta-analysis of 32 studies showed higher vitamin A levels in women with GDM compared to women without GDM in the first trimester, at 24 to 28 weeks and more than 28 weeks of pregnancy.
“A recent meta-analysis of 32 studies showed higher vitamin A levels in women with GDM compared to women without GDM in the first trimester, at 24 to 28 weeks and more than 28 weeks of pregnancy.”
From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [129]
The Abstract > Results reports that 32 studies were included and that circulating RBP4 levels were higher in women with GDM at all three stated pregnancy stages. The claim substitutes vitamin A levels for RBP4 levels; the paper reports the latter, not the former. No page number was provided for this passage. (LLM, conf=0.90)
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- Authors
- Leca, B. M., Kite, C., Lagojda, L., Davasgaium, A., Dallaway, A., Chatha, K. K., Randeva, H. S., & Kyrou, I.
- Affiliations
- University Hospital Coventry (GB)
- University of Wolverhampton (GB)
- Agricultural University of Athens (GR)
- Corresponding author
- Leca, Bianca M.
- Venue
- Frontiers in Public Health
- Publisher
- Frontiers Media SA
- Published
- 2024-03-12
- Volume
- 12
- Pages
- 1348970-1348970
- ISSN
- 2296-2565 (ISSN-L)
- PMC
- PMC10964926
- OpenAlex
- W4392702375
- Cited by
- 13
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 1
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Public Health (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure (Coventry University) (publishedVersion, cc-by)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Wolverhampton Intellectual Repository and E-Theses (University of Wolverhampton) (submittedVersion, cc-by)
- Funders
- University Hospitals Coventry and Warwickshire NHS Trust
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- retinol-binding protein 4, gestational diabetes mellitus, adipokines, lipocalin, pregnancy, circulating biomarkers, first trimester, second trimester, third trimester
- MeSH terms
- Female, Humans, Pregnancy, Prenatal Care, Biomarkers, Diabetes, Gestational, Retinol-Binding Proteins, Plasma
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