Background Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive. Objectives The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes. Methods PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model. Results Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): −14.15 mg/dL; 95% CI: −17.36, −10.93 mg/dL], 2-h postprandial glucose (WMD: −36.85 mg/dL; 95% CI: −62.05, −11.65 mg/dL), fasting insulin (WMD: −1.82 mU/L; 95% CI: −3.10, −0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: −0.73; 95% CI: −1.22, −0.24), glycated hemoglobin (WMD: −0.55%; 95% CI: −0.84, −0.27%), and high-sensitivity C-reactive protein (WMD: −1.31 mg/L; 95% CI: −2.05, −0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement. Conclusions Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes. This trial was registered at PROSPERO as CRD42018111838.

Context Iron overload is a known risk factor for type 2 diabetes (T2D); however, both iron overload and iron deficiency have been associated with metabolic disorders in observational studies. Objective Using Mendelian randomization (MR), we assessed how genetically predicted systemic iron status affected T2D risk. Design and Methods A two-sample MR analysis was used to obtain a causal estimate. We selected genetic variants strongly associated (P < 5×10 −8) with four biomarkers of systemic iron status from a study involving 48,972 subjects performed by the Genetics of Iron Status consortium and applied these biomarkers to the T2D case-control study (74,124 cases and 824,006 controls) performed by the Diabetes Genetics Replication and Meta-analysis consortium. The simple median, weighted median, MR-Egger, MR analysis using mixture-model, weighted allele scores, and MR based on Bayesian model averaging approaches were used for the sensitivity analysis. Results Genetically instrumented serum iron (OR: 1.07; 95% CI: 1.02–1.12), ferritin (OR: 1.19; 95% CI: 1.08–1.32), and transferrin saturation (OR: 1.06; 95% CI: 1.02–1.09) were positively associated with T2D. In contrast, genetically instrumented transferrin, a marker of reduced iron status, was inversely associated with T2D (OR: 0.91; 95% CI: 0.87–0.96). Conclusions Genetic evidence supports a causal link between increased systemic iron status and increased T2D risk. Further studies involving various ethnic backgrounds based on individual-level data and studies regarding the underlying mechanism are warranted for reducing the risk of T2D.

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db / db mice, obese ob / ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5 -deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5 -deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5 - mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions. Electronic supplementary material The online version of this article (10.1007/s13238-018-0580-1) contains supplementary material, which is available to authorized users.

T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2d) and C57BL/6 mice (H-2b) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4+ T-cell epitopes and most of which were CD8+ T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2b and H-2d mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity.