ArticleDiabetes2012
Diabetes-associated common genetic variation and its association with GLP-1 concentrations and response to exogenous GLP-1.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Multidimensional Predictors of Tirzepatide Efficacy: Clinical, Genetic, and Molecular Biomarkers for Glycemic, Weight, and Organ Protection.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Longitudinal Effect of Diabetes-Associated Variation in TCF7L2 on Islet Function in Humans.Diabetes · 2024Article
- The Effect of Diabetes-Associated Variation inMetabolic syndrome and related disorders · 2022Article
- Methylation status of vault RNA 2-1 promoter is a predictor of glycemic response to glucagon-like peptide-1 analog therapy in type 2 diabetes mellitus.BMJ open diabetes research & care · 2021Article
- No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect.Endocrine connections · 2020Article
- Pharmacogenetics of Type 2 Diabetes-Progress and Prospects.International journal of molecular sciences · 2020Review
- Fasting glucagon concentrations are associated with longitudinal decline of β-cell function in non-diabetic humans.Metabolism: clinical and experimental · 2020Article
- Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine.Diabetes/metabolism research and reviews · 2019Review
- Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes.Diabetology & metabolic syndrome · 2019Article
- What Can Diabetes-Associated Genetic Variation in TCF7L2 Teach Us About the Pathogenesis of Type 2 Diabetes?Metabolic syndrome and related disorders · 2018Review
- Walking a fine line between β-cell secretion and proliferation.The Journal of biological chemistry · 2018Review
- Diabetes-Associated Variation in TCF7L2 Is Not Associated With Hepatic or Extrahepatic Insulin Resistance.Diabetes · 2016Article
- Article
- Genetics of drug response in type 2 diabetes.Current diabetes reports · 2015Review
- Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass.Human molecular genetics · 2015Article
- Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.Journal of diabetes research · 2015Article
- Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?World journal of gastroenterology · 2014Review
- Untangling the interplay of genetic and metabolic influences on beta-cell function: Examples of potential therapeutic implications involving TCF7L2 and FFAR1.Molecular metabolism · 2014Review
- The sum of many parts: potential mechanisms for improvement in glucose homeostasis after bariatric surgery.Current diabetes reports · 2014Review
- Personalized management of hyperglycemia in type 2 diabetes: reflections from a Diabetes Care Editors' Expert Forum.Diabetes care · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanisms by which common genetic variation predisposes to type 2 diabetes remain unclear. The disease-associated variants in TCF7L2 (rs7903146) and WFS1 (rs10010131) have been shown to affect response to exogenous glucagon-like peptide 1 (GLP-1), while variants in KCNQ1 (rs151290, rs2237892, and rs2237895) alter endogenous GLP-1 secretion. We set out to validate these observations using a model of GLP-1-induced insulin secretion. We studied healthy individuals using a hyperglycemic clamp and GLP-1 infusion. In addition, we measured active and total GLP-1 in response to an oral challenge in nondiabetic subjects. After genotyping the relevant single nucleotide polymorphisms, generalized linear regression models and repeated-measures ANCOVA models incorporating potential confounders, such as age and BMI, were used to assess the associations, if any, of response with genotype. These variants did not alter GLP-1 concentrations in response to oral intake. No effects on β-cell responsiveness to hyperglycemia and GLP-1 infusion were apparent. Diabetes-associated variation (T allele at rs7903146) in TCF7L2 may impair the ability of hyperglycemia to suppress glucagon (45 ± 2 vs. 47 ± 2 vs. 60 ± 5 ng/L for CC, CT, and TT, respectively, P = 0.02). In nondiabetic subjects, diabetes-associated genetic variation does not alter GLP-1 concentrations after an oral challenge or its effect on insulin secretion.
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