Calcium supplementation and the risk of type 2 diabetes†

Abstract

Alterations in calcium homeostasis are critical for the development of type 2 diabetes (T2D), but its specific impacts on this disease are unclear. We aimed to evaluate whether the potential effect is causal. In a two-sample Mendelian randomization (TSMR) analysis, we evaluated if genetic signature predicting supplemental intake of calcium affects risks of T2D. The data on calcium supplementation (N = 461 384) were obtained from the IEU open GWAS project. The T2D GWAS dataset (N = 933 970) was provided by the DIAbetes genetics replication and meta-analysis consortium. We chose inverse variance weighting as the primary TSMR technique. Finally, we analyzed the association between calcium supplementation and T2D by mining The United States Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004 Q1–2024 Q3). A disproportionality analysis was performed to evaluate calcium safety profiles using the reporting odds ratio. Our TSMR analysis showed the role of calcium supplementation in increasing the risk of T2D (OR: 3.40, 95% CI: 1.12–10.38, P = 0.031). Mining of the FAERS database showed 56 T2D side effects among 23 368 adverse events of the drug calcium, supporting the association between calcium use and a high risk of T2D (ROR: 4.27, 95% CI: 3.28–5.55, P < 0.0001). As promoting calcium intake is found to increase the risk of T2D, clinical and public health decisions should be guided accordingly.