Blood manganese level and gestational diabetes mellitus: a systematic review and meta-analysis

Background: Previous studies evaluating the relationship between blood manganese (Mn) level and gestational diabetes mellitus (GDM) in pregnant women showed inconsistent results. A systematic review and meta-analysis was therefore performed to investigate the above association. Methods: Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library and Web of Science from database inception to 10 March 2023. Two authors independently performed database search, literature identification and data extraction. A randomised-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. Subgroup analysis was performed to evaluate the influence of study characteristics on the results of the meta-analysis. Results: Six datasets from five observational studies, involving 91,249 pregnant women were included in the meta-analysis. Among the participants, 3597 (3.9%) were diagnosed as GDM. Overall, pooled results showed that a high blood level of Mn was associated with a higher risk of GDM (compared between women with highest versus lowest category blood Mn, odds ratio: 1.31, 95% confidence interval: 1.19-1.44, p <.001) with no significant heterogeneity (p for Cochrane Q-test = 0.93, I-2 = 0%). Subgroup analyses according to study design, mean maternal age, matrix or methods for measuring blood Mn, and the incidence of GDM also showed consistent results (p for subgroup difference all >.05). Conclusions: Results of the meta-analysis suggest that a high blood Mn level may be a risk factor of GDM in pregnant women. Studies are needed to determine the underlying mechanisms, and to investigate if the relationship between blood Mn level and GDM is dose-dependent. PLAIN LANGUAGE SUMMARY Changes of blood manganese (Mn) have been suggested to be involved in the pathogenesis of diabetes. However, the relationship between blood Mn level and gestational diabetes mellitus (GDM) in pregnant women remains undetermined. Our study represents the first systematic review and meta-analysis to investigate the potential association between blood Mn concentration and the risk of GDM. In this meta-analysis, we pooled the results of six datasets from five observational and showed that compared to pregnant women with the lowest category of blood Mn level, those with the highest category of blood Mn level were associated with a higher risk of GDM. These results suggest that a high blood concentration of Mn in pregnant women may be a risk factor of GDM.