Environmental Cadmium Exposure and Type 2 Diabetes Mellitus Risk: An Overview of Systematic Reviews

Type 2 diabetes mellitus (T2DM) is a serious metabolic disorder impacting millions globally. A full understanding of the mechanisms implicated in diabetes genesis remain elusive, but exposure to environmental endocrine disruptors has emerged as a potential association of diabetes. Cadmium (Cd) has been investigated for its diabetogenic potential, yet the reported evidence is inconsistent. This overview of systematic reviews reports the association between Cd exposure and T2DM risk globally. Systematic reviews were identified by searching Medline, Embase, Web of Science, GEOBASE, BIOSIS Previews, and Cochrane Database of Systematic Reviews. Two reviewers independently completed screening, data abstraction, risk of bias evaluation, and confidence in level of evidence assessments using GRADE. The primary outcome involved estimating the association between Cd exposure, defined through measurement of Cd in urine (U-Cd) or blood (B-Cd), and T2DM. The quantitative data synthesis was conducted at the primary study level. While there was a trend for U-Cd (OR = 1.30, 95% CI 1.00–1.68) association with diabetes risk, B-Cd (OR = 1.37, 95% CI 1.02–1.83) levels were associated with diabetes risk. The risk of bias was high in 4 out of 5 included systematic reviews, and GRADE rating was very low. In conclusion, while current evidence suggests a link between cadmium levels and T2DM in the general population, these results should be interpreted with caution due to the methodological limitations of current studies, and additional studies should be undertaken to clarify this question. Systematic Review Registration: PROSPERO CRD42019125956.