ArticleNature metabolism2020
DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Association between glycated hemoglobin variability and risk of diabetic kidney disease and diabetic retinopathy in diabetic patients: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease.Nature communications · 2022Pooled it
- Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial.Translational psychiatry · 2022Trial
- Transient elevation in cellular glucose uptake exacerbates pressure overload-induced cardiac hypertrophy and dysfunction.Epigenetics · 2026Article
- Endurance exercise elicits a hepatic memory associated with improved metabolic function and protein secretion.Molecular metabolism · 2026Article
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- Epigenetic biomarkers in inflammatory bowel diseases-computational challenges and opportunities.Journal of Crohn's & colitis · 2026Review
- Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.Diabetologia · 2026Article
- Epigenetic alterations in type 1 diabetes and their association with poor glycemic control: the SED1-EPI substudy.Scientific reports · 2026Article
- Metabolic memory in diabetic complications: evidence for persistent cellular states and limits of therapeutic reversal.Frontiers in endocrinology · 2026Review
- Epigenome-wide mediation analysis identified Cytosine-phosphate-Guanine sites linking environmental factors with diabetes indicators.Epigenomics · 2026Article
- Recurrent single-CpG methylation differences and incomplete segregation in familial type 1 diabetes.Frontiers in immunology · 2026Article
- The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden.Current medicinal chemistry · 2026Review
- Decoding the Adipocyte Epigenome: Differentiation, Metabolic Memory, and Obesity.Journal of obesity & metabolic syndrome · 2025Review
- Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.Cell reports. Medicine · 2025Review
- Major Common Hallmarks and Potential Epigenetic Drivers of Wound Chronicity and Recurrence: Hypothesis and Reflections.International journal of molecular sciences · 2025Review
- Established and Emerging Roles of Epigenetic Regulation in Diabetic Cardiomyopathy.Diabetes/metabolism research and reviews · 2025Review
- Therapeutic Plasma Exchange: Current and Emerging Applications to Mitigate Cellular Signaling in Disease.Biomolecules · 2025Review
- The NIDDK Takes on the Complications of Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.Diabetes care · 2025Review
- DNA methylation and 28 year incidence of two neuropathy phenotypes in type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications cohort study.Diabetologia · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Metabolic memory, the persistent benefits of early glycaemic control on preventing and/or delaying the development of diabetic complications, has been observed in the Diabetes Control and Complications Trial (DCCT) and in the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study, but the underlying mechanisms remain unclear. Here, we show the involvement of epigenetic DNA methylation (DNAme) in metabolic memory by examining its associations with preceding glycaemic history, and with subsequent development of complications over an 18-yr period in the blood DNA of 499 randomly selected DCCT participants with type 1 diabetes who are also followed up in EDIC. We demonstrate the associations between DNAme near the closeout of DCCT and mean HbA1c during DCCT (mean-DCCT HbA1c) at 186 cytosine-guanine dinucleotides (CpGs) (FDR < 15%, including 43 at FDR < 5%), many of which were located in genes related to complications. Exploration studies into biological function reveal that these CpGs are enriched in binding sites for the C/EBP transcription factor, as well as enhancer/transcription regions in blood cells and haematopoietic stem cells, and open chromatin states in myeloid cells. Mediation analyses show that, remarkably, several CpGs in combination explain 68-97% of the association of mean-DCCT HbA1c with the risk of complications during EDIC. In summary, DNAme at key CpGs appears to mediate the association between hyperglycaemia and complications in metabolic memory, through modifying enhancer activity at myeloid and other cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.