Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

TLDR

Vascular complications drive morbidity and mortality in diabetes, and early intensive glycemic control produces a persistent benefit known as metabolic memory, whose mechanisms remain unclear. The study compared two groups of type 1 diabetic patients, with and without complications, using paired genomic DNA samples taken 16–17 years apart to demonstrate persistent DNA methylation at loci linked to complications. The findings provide direct evidence linking DNA methylation changes to metabolic memory, supporting an epigenetic mechanism for diabetic complications.

Abstract

Significance Vascular complications are the main cause of morbidity and mortality in the diabetic population. Clinical trials of diabetic complications show a persistence of benefit from early application of intensive therapy for glycemic control in diabetic patients, a phenomenon referred to as metabolic memory. The mechanisms underlying metabolic memory are not fully understood. In this study, using two groups of type 1 diabetic patients with and without complications development and two sets of genomic DNAs collected 16–17 y apart from the same patients, we showed a persistency of DNA methylation over time at key genomic loci associated with diabetic complications. These data provide direct evidence of a relationship between epigenetics (DNA methylation variations) and human metabolic memory, supporting an epigenetic mechanism.