Background: Although previous studies suggested the protective effect of zinc for type-2 diabetes, the unitary causal effect remains inconclusive.
Objective: We investigated the causal effect of zinc as a single intervention on glycemic control in type-2 diabetes patients, using a systematic review of RCTs and two-sample Mendelian randomization (MR).
Methods: Four outcomes were identified: fasting blood glucose/fasting glucose, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and serum insulin/fasting insulin level. In the systematic review, four databases were searched up to June 2021. Results were synthesized through the random-effects meta-analysis. Single nucleotide polymorphisms (SNPs) that are independent and are strongly related to zinc supplements were selected from MR-base to perform the two-sample MR with inverse-variance weighted (IVW) coefficient.
Results: In the systematic review, 14 trials were included. The zinc supplement led to a significant reduction in the post-trial mean of fasting blood glucose (mean difference (MD): -26.52, 95%CI: -35.13, -17.91), HbA1C (MD: -0.52, 95%CI: -0.90, -0.13), and HOMA-IR (MD: -1.65, 95%CI: -2.62, -0.68), compared to the control group. In the two-sample MR, zinc supplement with 2 SNPs associated with lower fasting glucose (IVW coefficient: -2.04, 95%CI: -3.26, -0.83), but not specified type-2 diabetes.
Conclusion: Although the study was limited by the few trials (review) and SNPs (two-sample MR), we demonstrated that the single zinc supplementary improved glycemic control among type-2 diabetes patients with causal evidence to a certain extent.