Trial reportThe Journal of clinical endocrinology and metabolism2011
Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism.
Trial report in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled 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.
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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- 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
- Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.PloS one · 2013Pooled it
- Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in the Setting of Glucokinase Regulatory Protein Inhibition: Glucokinase Regulatory Protein-Leu446Pro Variant in Look AHEAD.Circulation. Cardiovascular genetics · 2016Trial
- Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant.Molecular metabolism · 2026Article
- Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant.bioRxiv : the preprint server for biology · 2026Article
- Plasma inflammatory proteome profiles identify MASLD among children with overweight or obesity.Cardiovascular diabetology · 2025Article
- Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.Journal of translational medicine · 2024Article
- GlycA and CRP Are Genetically Correlated: Insight into the Genetic Architecture of Inflammageing.Biomolecules · 2024Article
- En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH.Cell · 2022Article
- Polygenic Risk of Hypertriglyceridemia Is Modified by BMI.International journal of molecular sciences · 2022Article
- Distinguishing the lipid profile of GCK-MODY patients and its correlation with hsCRP levels.Frontiers in endocrinology · 2022Article
- Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations.Scientific reports · 2020Article
- The Continuing Evolution of Precision Health in Type 2 Diabetes: Achievements and Challenges.Current diabetes reports · 2019Review
- Article
- The GCKR Gene Polymorphism rs780094 is a Risk Factor for Gestational Diabetes in a Brazilian Population.Journal of clinical laboratory analysis · 2017Article
- Leveraging Genetics to Advance Type 2 Diabetes Prevention.PLoS medicine · 2016Article
- Polymorphisms in the GCKR are associated with serum lipid traits, the risk of coronary artery disease and ischemic stroke.International journal of clinical and experimental medicine · 2015Article
- Article
- Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women.Nutrition & diabetes · 2014Article
- Maternal genotype and gestational diabetes.American journal of perinatology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
contextGlucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels and, paradoxically, reductions in diabetes incidence, fasting glucose levels, and insulin resistance. OBJECTIVE, SETTING, AND PATIENTS: We sought to replicate these associations and evaluate interactions with lifestyle and metformin interventions in the multiethnic Diabetes Prevention Program (DPP). INTERVENTIONS AND
main outcome measuresWe genotyped the two GCKR SNP in 3346 DPP participants and evaluated association with progression to diabetes and both baseline levels and changes in triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), oral disposition index, and inflammatory markers along with their interactions with DPP interventions.
resultsGCKR variation did not predict development of type 2 diabetes. At baseline, the 446L allele was associated with higher triglyceride and C-reactive protein levels (both P < 0.0001) and lower fasting glucose (P = 0.001) and HOMA-IR (P = 0.06). The lifestyle intervention was associated with a decrease in magnitude of the effect of the 446L allele on triglyceride levels (interaction P = 0.04). Metformin was more effective in reducing HOMA-IR in carriers of the P446 allele (interaction P = 0.05).
conclusionsIntensive lifestyle intervention appears to partially mitigate the effect of the 446L allele on higher triglycerides, whereas the P446 allele appears to enhance responsiveness to the HOMA-IR-lowering effect of metformin.
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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.