Evidence mapPaperPMID 41547928Full record

ArticleBiomarker research2026

Stratifying high-risk prediabetes clusters using blood-based epigenetic markers.

Amandeep Singh, Reiner Jumpertz-von Schwartzenberg, Robert Wagner, Leontine Sandforth, Arvid Sandforth, Markus Jähnert, Marlene Ganslmeier, Stefan Kabisch, Nikolaos Perakakis, Hubert Preißl and 6 more

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Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Amandeep SinghDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Reiner Jumpertz-von SchwartzenbergGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Robert WagnerGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Leontine SandforthGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Arvid SandforthGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Markus JähnertDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Marlene GanslmeierGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Stefan KabischGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Nikolaos PerakakisGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Hubert PreißlGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Andreas FritscheGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Norbert StefanGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Dirk WalterMax Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476, Potsdam, Golm, Germany.
Meriem Ouni *Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. meriem.ouni@dife.de.
Andreas L Birkenfeld *German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Annette Schürmann *Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreviously, we identified six prediabetes clusters, three at moderate and three at high-risk for type 2 diabetes and/or complications. While this novel classification could enable earlier and improved disease prevention, it relies on intensive clinical phenotyping. Here, we developed a machine learning workflow to identify blood-based epigenetic markers to distinguish between prediabetes clusters.

methodsDNA methylation was profiled in blood cells of different cohorts including individuals that belong to clusters 2 (low-risk), 3, 5, and 6 (each high-risk) and data was subjected to a machine learning workflow.

resultsIn a discovery cohort (n = 187), we identified 1,557 CpG sites as predictors for clusters 2, 3, 5, and 6. These CpGs were sufficient to distinguish between individuals belonging to the high-risk clusters 3, 5 and 6 in an independent replication cohort (n = 146) with an accuracy of 92%. Between 300 and 339 CpG sites were specific for each cluster and the corresponding genes linked to TGF-β receptor and calcium signaling (cluster 3), MAPK cascade and ECM organization (cluster 5), and Wnt/SMAD signaling (cluster 6), mirroring the metabolic deterioration observed in each cluster.

conclusionsWithout the need for complex clinical measurements, the identified blood-based epigenetic signatures may improve the detection of individuals at high-risk of developing diabetes and complications and point to the potential molecular mechanism responsible for the heterogeneity in prediabetes. These markers highlight the potential of the blood epigenome as an effective proxy for predicting future complications and make extensive clinical assessments obsolete, enabling the identification of clusters in larger populations.

Indexed as

Epigenetic (bio)-markersMachine learningPrediabetesPrognostic toolsRisk stratification

Identifiers

PMID41547928
PMCPMC12829285

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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 Socratic graph.