ArticleDiabetes2010
Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 14 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.
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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.
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Who cites it
148 citing papers in PubMed, 14 syntheses or guidelines pooled it, 256 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
- GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.Nature genetics · 2023Pooled it
- Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.Diabetologia · 2021Pooled it
- Pooled it
- Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.The Journal of clinical investigation · 2015Pooled it
- Pleiotropic genes for metabolic syndrome and inflammation.Molecular genetics and metabolism · 2014Pooled it
- Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.Diabetes · 2014Pooled it
- A central role for GRB10 in regulation of islet function in man.PLoS genetics · 2014Pooled it
- Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals.Diabetologia · 2013Pooled it
- Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance.Diabetologia · 2013Pooled it
- Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses.Human molecular genetics · 2012Pooled it
- Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.Nature genetics · 2012Pooled it
- Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism.Diabetologia · 2012Pooled it
- Association of genetic Loci with glucose levels in childhood and adolescence: a meta-analysis of over 6,000 children.Diabetes · 2011Pooled it
- Statins Are Associated With Increased Insulin Resistance and Secretion.Arteriosclerosis, thrombosis, and vascular biology · 2021 · on this mapTrial
- Trial
- Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.The pharmacogenomics journal · 2015Trial
- Intake levels of dietary long-chain PUFAs modify the association between genetic variation in FADS and LDL-C.Journal of lipid research · 2012Trial
- Effects of genetic variants previously associated with fasting glucose and insulin in the Diabetes Prevention Program.PloS one · 2012Trial
- The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals.Diabetologia · 2011Trial
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
68 authors at 1 institution in 1 country.
Funding
Abstract
OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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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.