Type 2 diabetes mellitus and zinc dysregulation: From basic and epidemiological evidence to interventions

Abstract

Background: Complex cellular and systemic changes in Zn levels have been reported through different stages of Type 2 Diabetes (T2DM) onset and progression.

Methods: We summarize available evidence on Zn and T2DM, including mechanistic and epidemiological/clinical studies with a focus on Zn pathophysiology, interpretation of Zn biomarkers, and associations of Zn status and T2DM across different populations.

Results: Misdistribution of Zn in insulin-producing ß-cells are likely key contributors to ß-cell failure in T2DM, with genetic variants in ZnT8 transporters playing an important role. Epidemiological evidence has documented increased urinary Zn and decreased plasma and blood Zn in persons with established T2DM. Changes in Zn biomarkers have been prospectively associated with increased risk of T2DM in pre-diabetes and healthy adults before hyperglycemia occurs. Some studies suggest that Zn supplementation could modify glycemic endpoints in T2DM participants, but evidence is insufficient in healthy adults. Zn biomarkers, including isotopes, can provide novel approaches for T2DM risk assessment and management at different disease stages.

Conclusions: Dysregulation of Zn metabolism occurs early in T2DM development with ß-cell failure playing a central role. Additional research is needed to connect mechanistic evidence and pathophysiological changes associated with various stages of T2DM progression.

Keywords: Beta cells; Biomarkers; Pancreatic islets; Supplementation; Type 2 diabetes; Zinc; ZnT8.