Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis

Abstract

Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND “gestational diabetes.” Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.

Keywords:

• Leptin
• TNF-α
• IL-6
• inflammation
• cytokine
• gestational diabetes

Authors’ contributions

EH, performed the search and title and abstract screening, reviewed the full-text articles, extracted and analyzed data, and prepared the manuscript. ZM, contributed to performing the search, reviewing the full-text articles and extracting of data. ASA, contributed to performing the search and data analyses. RA and GM, interpreted the results and revised the manuscript. All authors complied with the final version submitted for publication.

Disclosure statement

The authors have no conflicts of interest.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.