A comprehensive review on the latest progressions of cell-free DNA in diabetes and related microvascular or macrovascular complications.

Diabetes is a global health problem which affected one in eleven adults in the world, and it has become the ninth leading cause of death. Diabetes is a chronic metabolic disorder, its systemic inflammation state might cause long-term complications, including macrovascular (including cardiovascular disease) and microvascular complications (including diabetic retinopathy and nephropathy). Circulating cell-free DNAs (cfDNAs) play important roles in diagnosing or monitoring diabetes or its related complications. The current review comprehensively summarized the latest study progresses of cfDNA-related applications as potential biomarkers in diabetes and diabetic complications, including type 1 diabetes, type 2 diabetes, diabetic retinopathy, diabetic nephropathy, and gestational diabetes mellitus. CfDNAs contain a lot of important molecular information in these applications of diabetic diseases, such as their genetic (mutation or copy number) or epigenetic (methylation or hydroxymethylation) content, organelle origin (nuclear or mitochondrial DNA), DNA concentration and DNA fragment size. In addition, we also discussed the existed limitations and future directions of cfDNA-related studies in diabetes and its complications. This review will provide important reference for exploring the clinical application value of cfDNAs in diabetes and diabetic complications.