Type-2 diabetes epigenetic biomarkers: present status and future directions for global and Indigenous health

Type-2 diabetes is a systemic condition with rising global prevalence, disproportionately affecting Indigenous communities worldwide. Recent advances in epigenomics methods, particularly in DNA methylation detection, have enabled the discovery of associations between epigenetic changes and Type-2 diabetes. In this review, we summarise DNA methylation profiling methods, and discuss how these technologies can facilitate the discovery of epigenomic biomarkers for Type-2 diabetes. We critically evaluate previous DNA methylation biomarker studies, particularly those using microarray platforms, and advocate for a shift towards sequencing-based approaches to improve genome-wide coverage. Furthermore, we emphasise the need for biomarker studies that include genetically diverse populations, especially Indigenous communities who are significantly impacted by Type-2 diabetes. We discuss research approaches and ethical considerations that can better facilitate Type-2 diabetes biomarker development to ensure that future genomics-based precision medicine efforts deliver equitable health outcomes. We propose that by addressing these gaps, future research can better capture the genetic and environmental complexities of Type-2 diabetes among populations at disproportionate levels of risk, ultimately leading to more effective diagnostic and therapeutic strategies.