Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis

Zinc supplementation has therapeutic effects on cardiovascular disease (CVD) risk factors, including dyslipidemia, hyperglycemia, and inflammation as the main contributors to CVD pathogenesis. Since CVD is a major cause of mortality among people with type 2 diabetes mellitus (T2DM), this study aimed to overview the potential effects of zinc supplementation on CVD risk factors in T2DM patients. To determine appropriate randomized clinical trials (RCTs) investigating the effects of zinc supplementation on CVD risk factors, electronic sources including PubMed, Web of Science, and Scopus were systematically searched until January 2023. The heterogeneity of trials was checked using the I2 statistic. According to the heterogeneity tests, random-effects models were estimated, and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI). Of the 4004 initial records, 23 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), hemoglobin A1C (HbA1C), and C-reactive protein (CRP), while high-density cholesterol (HDL) concentrations showed an elevation after zinc supplementation. In addition to statistical significance, the effect of zinc supplementation on most of the variables was clinically significant; however, the quality of evidence in the included studies is regarded as low or very low for most variables. Our study demonstrated that zinc supplementation has beneficial effects on glycemic control markers, lipid profile, and CRP levels as a classic marker of inflammation in T2DM. Due to the high degree of heterogeneity between studies and the low rate of quality in them, further well-designed studies are necessitated to strengthen our findings.