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Inflammatory cytokines, leptin, tumor necrosis factor-α, and interleukin-6 may be key to understanding the development of gestational diabetes mellitus, according to a recent systematic review and meta-analysis.

  • The systematic review and meta-analysis included 24 studies, providing an in-depth look at the relationship between leptin, TNF-α, IL-6, and the risk of gestational diabetes.
  • Findings show that higher circulating leptin, TNF-α, and IL-6 levels are significantly associated with increased risk of gestational diabetes.
  • Further longitudinal studies with larger sample sizes are necessary for a more comprehensive evaluation of these findings.

Gestational diabetes mellitus (GDM), the most common complication during pregnancy, has significant maternal and neonatal health implications. Insulin resistance, which typically begins in the second trimester of pregnancy and progressively escalates to levels similar to those detected in type 2 diabetes mellitus, is thought to play a crucial role in the onset of GDM. This increase in insulin resistance is attributed to increased maternal adiposity and placental hormones.

In recent years, the role of adipokines—cytokines derived from adipose tissue, such as leptin, tumor necrosis factor-α (TNF-α), and IL-6—has been investigated as potential mediators of insulin resistance. These cytokines, which are also produced by the placenta, have been linked to an increased risk of GDM, prompting the need for a more accurate estimate of their effect size.

Investigating the Link Between Specific Biomarkers and Gestational Diabetes

A meta-analysis published in Gynecological Endocrinology that included 24 studies revealed significant associations between elevated levels of leptin, TNF-α, and IL-6, and the risk of GDM.

The pooled estimates showed an odds ratio (OR) of 1.16 for GDM risk with higher circulating leptin, an OR of 1.35 with IL-6, and an OR of 1.28 with TNF-α. These findings suggest that these cytokines may not only be implicated in the pathogenesis of GDM but could also be used as potential biomarkers for assessing GDM risk.

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Looking Ahead at Potential Applications

The findings of this systematic review and meta-analysis highlight the potential role of cytokines in the development of GDM. However, some degree of heterogeneity was observed across studies, suggesting the need for further investigation to explore potential sources of this variation.

Future research should consider factors such as small sample sizes, population characteristics, and variables used as confounders that could contribute to inconsistency in results. Moreover, additional longitudinal studies with larger sample sizes are needed for a more comprehensive evaluation of these findings.

Considering the rising incidence of GDM and its associated comorbidities, there is an urgent need for improved risk assessment models using a combination of clinical and biochemical data. Such research could significantly advance our understanding of GDM, ultimately contributing to the development of more effective preventative and therapeutic strategies.


Hosseini, E., Mokhtari, Z., Kwon, D., Mishra, G. D., & Amani, R. (2023). Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis. Gynecological Endocrinology, 39(1). https://doi.org/10.1080/09513590.2023.2183049