Evidence mapPaperPMID 41335123Full record

ArticleDiabetes care2026

Integrative Metabolomics of Targeted and Nontargeted Analyses in T2D Progression.

Jianhong Ge, Siyu Han, Mengya Shi, Makoto Harada, Shixiang Yu, Jiaqi Zheng, Cornelia Prehn, Jerzy Adamski, Gabi Kastenmüller, Sabrina Schlesinger and 7 more

Abstract read
In one paragraph

Article in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jianhong GeTUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
Siyu HanInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Mengya ShiTUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
Makoto HaradaInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Shixiang YuTUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
Jiaqi ZhengInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Cornelia PrehnMetabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Jerzy AdamskiInstitute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Gabi KastenmüllerInstitute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Sabrina SchlesingerInstitute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.ORCID 0000-0003-4244-0832
Wolfgang KoenigDeutsches Herzzentrum München, Technische Universität München, München, Germany.
Birgit LinkohrInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Barbara ThorandGerman Center for Diabetes Research (DZD), Partner Neuherberg, Neuherberg, Germany.
Karsten SuhreBioinformatics Core, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
Christian GiegerInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Annette PetersGerman Center for Diabetes Research (DZD), Partner Neuherberg, Neuherberg, Germany.
Rui Wang-SattlerInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID 0000-0002-8794-8229

Funding

China Scholarship Council (CSC) 202206010083German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria KORAGerman Federal Ministry of Health The German Diabetes CenterInnovative Medicines Initiative 2 Joint Undertaking (JU) No. 821508 (CARDIATEAM)
6 · The paper itself

Abstract

objectiveThis study aimed to identify metabolites characterizing the progression from normal glucose metabolism (NORM) to prediabetes (PreT2D) and type 2 diabetes (T2D), focusing on stage-specific metabolic shifts (early: NORM to PreT2D; late: PreT2D to T2D) and mechanistic relevance. RESEARCH DESIGN AND

methodsWe analyzed 8,240 observations from the KORA cohort, profiling 104 targeted and 312 nontargeted metabolites across three time points: baseline (S4) and follow-ups (F4 and FF4) spanning 14 years. Trajectory analyses of 1,050 individuals identified 211 incident PreT2D and 112 incident T2D cases. Linear mixed-effects models (basic: adjusted for age, sex, BMI, lifestyle; sensitivity: additionally adjusted for glycemic factors like fasting glucose, and cardiovascular factors such as systolic blood pressure (BP) were used to evaluate metabolic differences across glycemic states. Mediation and Mendelian randomization (MR) analyses examined mechanistic and causal relationships.

resultsWe identified 140 Bonferroni-significant metabolites (45 targeted, 109 nontargeted, 14 overlapping), including 68 early-stage metabolites (significant in PreT2D/T2D vs. NORM), primarily energy metabolism markers such as fatty acid oxidation metabolites (e.g., 37 lipids) and tricarboxylic acid cycle metabolites (e.g., citrate). Twenty late-stage metabolites (significant in T2D vs. PreT2D/NORM) included amino acids like branched-chain amino acids (BCAAs) and γ-glutamyl derivatives. Fewer significant associations were observed in incident cases. Sensitivity models validated 50% of early-stage but not late-stage metabolites. Fasting glucose mediated 35.1% of the γ-glutamyl-valine-T2D association, while MR analysis found no causal roles for C2, BCAAs, or γ-glutamyl-valine.

conclusionsEnergy metabolism shifts occur early, while amino acid alterations emerge later stages. These stage-specific signatures may guide diabetes prevention strategies.

Indexed as

Diabetes Mellitus, Type 2MetabolomicsAgedBlood GlucoseDisease ProgressionFemaleHumansMaleMiddle AgedPrediabetic StateBlood Glucose

Identifiers

PMID41335123
PMCPMC12824783

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.