Evidence map›Paper›PMID 41705646›Full record

SynthesisDiabetes, obesity & metabolism2026

Causal role of genetically predicted impairment of branched-chain amino acid catabolism on insulin secretion and insulin resistance in type 2 diabetes.

Xiangyu Zhou, Jiawen Lu, Zhenqian Wang, Kenneth King-Yip Cheng, Gloria Hoi-Yee Li

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
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

5 authors.

Xiangyu ZhouDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.ORCID https://orcid.org/0000-0001-8217-3391
Jiawen LuDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.ORCID https://orcid.org/0000-0003-2671-3028
Zhenqian WangDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.ORCID https://orcid.org/0000-0001-8700-0836
Kenneth King-Yip ChengDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.ORCID https://orcid.org/0000-0002-7274-0839
Gloria Hoi-Yee LiDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.ORCID https://orcid.org/0000-0003-0275-2356

Funding

Research Grants Council, University Grants Committee, Hong Kong C5044-23GResearch Grants Council, University Grants Committee, Hong Kong PF22-75980The Hong Kong Polytechnic University P0036848
6 · The paper itself

Abstract

backgroundElevated branched-chain amino acids (BCAAs; leucine, valine, isoleucine) are linked to type 2 diabetes (T2D) risk, characterised by defective insulin secretion in pancreatic β-cell and peripheral insulin resistance. Causative interaction between BCAA metabolism and these two diabetic pathogenesis remains unclear.

methodsUsing publicly available datasets from the European population, we conducted a meta-analysis of genome-wide association studies (GWAS), followed by multi-trait analysis of GWAS (MTAG), to identify genetic loci associated with BCAAs and their catabolites. Two-sample bidirectional Mendelian Randomisation (MR) examined putative causal associations of genetically determined BCAAs and their catabolites with 10 traits related to insulin and glucose metabolism. Sensitivity analyses evaluated robustness and specificity of observed associations.

resultsMTAG identified 57.14%, 59.09%, and 63.41% novel genetic loci for circulating leucine, valine and isoleucine, respectively. Genetically elevated valine had a significant association with increased insulin fold change during oral glucose challenge test (OGTT) (β [95% CI] = 0.135 [0.045, 0.225]), False discovery rate adjusted p-value (p

conclusionsOur genetic analysis indicates BCAA catabolism and insulin secretion/action interact with each other; their aberrance might form a vicious cycle promoting T2D progression.

Indexed as

Amino Acids, Branched-ChainDiabetes Mellitus, Type 2Insulin ResistanceInsulin SecretionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulinInsulin-Secreting CellsIsoleucineLeucineMendelian Randomization AnalysisPolymorphism, Single NucleotideValineAmino Acids, Branched-ChainInsulinIsoleucineLeucineValinebranched‐chain amino acids (BCAAs)genome‐wide association studyinsulin resistanceinsulin secretionMendelian randomisation analysistype 2 diabetes

Identifiers

PMID41705646
PMCPMC13071227

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

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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.