Effect of zinc supplementation in the management of type 2 diabetes: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of randomized controlled trials

The question of whether zinc supplementation may improve cardio-metabolic health in patients with type 2 diabetes mellitus (T2DM) remains controversial and require further evaluation. This study aimed to summarize the effectiveness of oral zinc supplementation in improving cardio-metabolic risk markers in people with T2DM. We searched PubMed, Scopus, and Web of Science from inception to April 2023, for randomized controlled trials (RCTs). RCTs of type 2 diabetic adults (aged ≥18 years) comparing zinc supplementation with placebo were included. We excluded studies if not randomized, involved co-supplementation, and were conducted in children or pregnant women. Glycemic indices, lipid profiles, blood pressure, anthropometric measure, c-reactive protein (CRP), creatinine, and serum zinc were extracted. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods. We used a random-effect model to perform the dose-response analysis. Effect sizes were presented as mean difference (MD) and 95% confidence interval (CI). 22 studies (n = 1442 participants) were included. The certainty of the evidence was rated as moderate to high. Zinc supplementation significantly reduced glycemic indices: including two-hour postprandial glucose (2hpp) (mean difference (MD): −34.34 mg/dl; 95%CI: −51.61∼ −17.07), fast blood sugar (FBS) (MD: −23.32 mg/dl; 95% CI: −33.81∼ −12.83), and hemoglobin A1c (HbA1c) (MD: −0.47; 95% CI: −0.71∼ −0.23). Zinc had a favorable effect on lipid profiles low-density lipoprotein (LDL) (MD: −10.76 mg/dl; CI: −17.79∼−3.73), triglyceride (TG) (MD: −18.23 mg/dl; CI: −32.81∼−3.65), total cholesterol (TC) (MD: −12.74 mg/dl; CI: −21.68∼−3.80), VLDL (MD: −5.39 mg/dl; CI: −7.35∼−3.43) and high-density lipoprotein (HDL) (MD: 4.04 mg/dl; CI: 0.96 ∼ 7.12). Systolic blood pressure (SBP) (MD): −3.64 mmHg; 95% CI: −6.77∼ −0.52), weight (MD: 1.00 kg; 95% CI: 0.34∼1.66), CRP (MD: −3.37 mg/l, 95% CI: −4.05∼ −2.70), and serum zinc (MD: 15.38 µg/dl; 95% CI: 10.74∼ 20.02) changed to a statistically significant extent with zinc supplementation. There was also a linear association between additional 10 mg/d zinc treatment with FBS, HbA1c, HDL, LDL, TG, TC, and serum zinc. A non-linear dose-response gradient was seen for FBS, HDL, and SBP (p < 0.05). Egger’s test showed no substantial publication bias. Our findings strongly suggest a potential beneficial effect of zinc supplementation on type 2 diabetic patients. Further high-quality research is needed to determine the optimal form, dosage, and duration of zinc supplementation for this population.