Evidence map›Paper›PMID 40346526›Full record

ArticleCardiovascular diabetology2025

Metabolic pathways mediating insulin resistance and gestational diabetes mellitus discovered by high-dimensional systematic Mendelian randomization.

Wei Chen, Mingjuan Luo, Jingyi Guo, Suna Wang, Dandan Yan, Xiaohui Feng, Yunting Huang, Tao Zeng, Li Shen, Rong Zhang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. 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

14 authors.

Wei Chen *Clinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mingjuan Luo *Department of Endocrinology and Metabolism, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Jingyi Guo *Clinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Suna WangClinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dandan YanDepartment of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
Xiaohui FengDepartment of Endocrinology and Metabolism, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Yunting HuangDepartment of Endocrinology and Metabolism, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Tao ZengGuangzhou National Laboratory, Guangzhou, China.
Li ShenClinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rong ZhangShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing YanShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cheng HuShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. alfredhc@sjtu.edu.cn.
Weituo ZhangSchool of Public Health, Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhangweituo@sjtu.edu.cn.
Xiangtian YuClinical Research Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. graceyu@sjtu.edu.cn.

Funding

Clinical Research Plan of SHDC SHDC2022CRS044Clinical Research Plan of SHDC SHDC2023CRS029Fundamental Research Funds for the Central Universities YG2023QNB20National Key Research and Development Program of China 2022YFA1004800National Key Research and Development Program of China 2022YFF1202100National Natural Science Foundation of China No.12371485Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Basic Scientific Research No. ynms202118
6 · The paper itself

Abstract

backgroundGestational diabetes mellitus (GDM), characterized by insulin resistance (IR) and β-cell dysfunction, is one of the most common complications of pregnancy with unmet needs of prevention methods.

objectiveTo investigate the causal role of insulin resistance and metabolic pathways in the pathogenesis of GDM with our proposed high-dimensional systematic Mendelian randomization (hdsMR) framework.

methodsCases with GDM and controls with normal glucose tolerance were recruited at the University of Hong Kong-Shenzhen Hospital from 2015 to 2018. A total of 566 participants (aged > 18 years), including 274 with GDM, were enrolled after excluding subjects with major chronic diseases or long-term use of medications affecting glycolipid metabolism. Clinical characteristics and serum samples were collected during the GDM screening stage, and the genome and metabolome were tested. A novel hdsMR framework was proposed to estimate the causal role of IR index (Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) and metabolic pathways in the pathogenesis of GDM.

resultsOur hdsMR method confirmed that HOMA-IR was causal to GDM (odds ratio, 1.17; 95% confidence interval, 1.04-1.32) and revealed that two metabolic pathways (glyoxylate and dicarboxylate metabolism pathway and lysine degradation pathway) mediated 14.6% and 8.4%, respectively, between HOMA-IR and GDM. In an independent validation cohort comprising 255 pre-diabetic individuals, we showed that both pathways could be intervened through diet (P < 0.05). Furthermore, glyoxylate and dicarboxylate metabolism pathway was significantly associated with adverse pregnancy outcomes in GDM.

conclusionsThese results indicated that targeting specific metabolic pathways through dietary intervention is worth exploring as a possible GDM prevention approach, and hdsMR is more efficient in finding causal mediating metabolic pathways than traditional MR methods.

Indexed as

Blood GlucoseDiabetes, GestationalEnergy MetabolismInsulinInsulin ResistanceMendelian Randomization AnalysisMetabolic Networks and PathwaysAdultBiomarkersCase-Control StudiesFemaleGenetic Predisposition to DiseaseHumansMetabolomicsPhenotypePregnancyBiomarkersBlood GlucoseInsulinAdverse pregnancy outcomeGestational diabetes mellitusInsulin resistanceMendelian randomizationMetabolic pathway

Identifiers

PMID40346526
PMCPMC12065323

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.