Trial reportProceedings of the National Academy of Sciences of the United States of America2016
Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
160 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.
- Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.eLife · 2020Pooled it
- DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty.Nature communications · 2017Pooled it
- Transient elevation in cellular glucose uptake exacerbates pressure overload-induced cardiac hypertrophy and dysfunction.Epigenetics · 2026Article
- Maternal Obesity Induces DNA Methylation Changes in the Kidneys and Blood of Rodent Offspring at Adulthood.Nutrients · 2026Article
- Endurance exercise elicits a hepatic memory associated with improved metabolic function and protein secretion.Molecular metabolism · 2026Article
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.Diabetologia · 2026Article
- Trained Immunity in Autoimmunity: Friend, Foe, or Therapeutic Target?Biomedicines · 2026Article
- Promising Biomarkers for Early Diagnosis: Advances in Understanding the Pathogenesis of Diabetic Peripheral Neuropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Mechanisms of diabetic kidney disease and established and emerging treatments.Nature reviews. Endocrinology · 2026Review
- Recurrent single-CpG methylation differences and incomplete segregation in familial type 1 diabetes.Frontiers in immunology · 2026Article
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- Metabolic memory in diabetic complications: evidence for persistent cellular states and limits of therapeutic reversal.Frontiers in endocrinology · 2026Review
- Review
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis.Cell reports. Medicine · 2025Review
- Established and Emerging Roles of Epigenetic Regulation in Diabetic Cardiomyopathy.Diabetes/metabolism research and reviews · 2025Review
- Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes.Cell reports. Medicine · 2025Article
- DNA methylation in chronic kidney disease.BMC nephrology · 2025Review
- Therapeutic Plasma Exchange: Current and Emerging Applications to Mitigate Cellular Signaling in Disease.Biomolecules · 2025Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.
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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.