Trial reportThe Journal of clinical investigation2007
Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
Trial report in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 391 papers, 10 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
391 citing papers in PubMed, 10 syntheses or guidelines pooled it, 824 citations in OpenAlex.
- Associations Between TCF7L2, PPARγ, and KCNJ11 Genotypes and Insulin Response to an Oral Glucose Tolerance Test: A Systematic Review.Molecular nutrition & food research · 2025Pooled it
- Association of TCF7L2 genetic variants rs12255372 and rs7903146 with the polycystic ovary syndrome risk: systemic review and meta-analysis.Journal of ovarian research · 2025Pooled it
- Gene-lifestyle interaction on risk of type 2 diabetes: A systematic review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2019Pooled it
- Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus.BMC medical genetics · 2018Pooled it
- Pooled it
- Association between TCF7L2 polymorphisms and gestational diabetes mellitus: A meta-analysis.Journal of diabetes investigation · 2017Pooled it
- Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism as a Risk Factor for Gestational Diabetes Mellitus: A Meta-Analysis.PloS one · 2016Pooled it
- The association between the rs11196218A/G polymorphism of the TCF7L2 gene and type 2 diabetes in the Chinese Han population: a meta-analysis.Clinics (Sao Paulo, Brazil) · 2015Pooled it
- Pooled it
- The Protective Effect of Transcription Factor 7-Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta-Analysis.Journal of diabetes research · 2015Pooled it
- Home consumption of two fortified balanced energy protein supplements by pregnant women in Burkina Faso.Maternal & child nutrition · 2021Trial
- Diabetes-associated genetic variation in TCF7L2 alters pulsatile insulin secretion in humans.JCI insight · 2020Trial
- Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1-Mediated Mechanism.The Journal of clinical endocrinology and metabolism · 2019Trial
- Trial
- Influence of TCF7L2 gene variants on the therapeutic response to the dipeptidylpeptidase-4 inhibitor linagliptin.Diabetologia · 2014Trial
- Association of TCF7L2 and LEPR gene variants (rs7903146 and rs1137101) with primary knee osteoarthritis in a northern Mexican Mestizo population.Clinical rheumatology · 2026Article
- Genetic Variants Associated with Response to GLP-1 Receptor Agonists in Diabetes and Obesity.Life (Basel, Switzerland) · 2026Review
- Association of PPARγ (rs1801282) and TCF7L2 (rs7903146) gene polymorphisms and susceptibility of Type 1 diabetes mellitus in Egyptian children.Journal, genetic engineering & biotechnology · 2026Article
- Integrative Clinical and Functional Characterization of theDiagnostics (Basel, Switzerland) · 2026Article
- A modality-aware CRISPR actionability framework for functional prioritization of genome-wide significant type 2 diabetes loci.Molecular genetics and genomics : MGG · 2026Article
331 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic variants in the gene encoding for transcription factor-7-like 2 (TCF7L2) have been associated with type 2 diabetes (T2D) and impaired beta cell function, but the mechanisms have remained unknown. We therefore studied prospectively the ability of common variants in TCF7L2 to predict future T2D and explored the mechanisms by which they would do this. Scandinavian subjects followed for up to 22 years were genotyped for 3 SNPs (rs7903146, rs12255372, and rs10885406) in TCF7L2, and a subset of them underwent extensive metabolic studies. Expression of TCF7L2 was related to genotype and metabolic parameters in human islets. The CT/TT genotypes of SNP rs7903146 strongly predicted future T2D in 2 independent cohorts (Swedish and Finnish). The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. Overexpression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion.
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Registered trials
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.