Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis

Background: Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. Objective: To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. Data source: After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. Study eligibility criteria: We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. Study appraisal and synthesis methods: Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. Results: In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. Limitations and conclusions: This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.