Trial reportDiabetologia2007
The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program.
Trial report in Diabetologia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00004992. Cited by 31 papers, 4 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.
Diabetes Prevention Program
Open the trial in the graphWho cites it
31 citing papers in PubMed, 4 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Genetics of Exercise and Diet-Induced Fat Loss Efficiency: A Systematic Review.Journal of sports science & medicine · 2024Pooled it
- G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- Interaction between Pro12Ala polymorphism of PPARγ2 and diet on adiposity phenotypes.Current atherosclerosis reports · 2014Pooled it
- No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.Diabetes · 2012Pooled it
- Common Variants in Lipid Metabolism-Related Genes Associate with Fat Mass Changes in Response to Dietary Monounsaturated Fatty Acids in Adults with Abdominal Obesity.The Journal of nutrition · 2019Trial
- Habitual consumption of long-chain n-3 PUFAs and fish attenuates genetically associated long-term weight gain.The American journal of clinical nutrition · 2019Trial
- Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look AHEAD trial.Human heredity · 2013Trial
- Association of type 2 diabetes susceptibility loci with one-year weight loss in the look AHEAD clinical trial.Obesity (Silver Spring, Md.) · 2012Trial
- Obesity susceptibility loci and dietary intake in the Look AHEAD Trial.The American journal of clinical nutrition · 2012Trial
- Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.Diabetes care · 2012Trial
- Immunogenetic Aspects of Sarcopenic Obesity.Genes · 2024Review
- Association of gene polymorphisms with body weight changes in prediabetic patients.Molecular biology reports · 2022Article
- Pro12Ala Polymorphism on the PPARFrontiers in physiology · 2020Article
- Article
- Dietary Fatty Acid Composition Modulates Obesity and Interacts with Obesity-Related Genes.Lipids · 2017Review
- The importance of gene-environment interactions in human obesity.Clinical science (London, England : 1979) · 2016Review
- Variation in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2015Article
- Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors.Pharmacogenomics · 2014Review
- PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study.Journal of translational medicine · 2014Article
- Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program.Arteriosclerosis, thrombosis, and vascular biology · 2012Review
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
aims/hypothesisPeroxisome proliferator-activated receptor gamma (PPARgamma), encoded by the PPARG gene, regulates insulin sensitivity and adipogenesis, and may bind polyunsaturated fatty acids (PUFA) and thiazolidinediones in a ligand-dependent manner. The PPARG proline for alanine substitution at position 12 (Pro12Ala polymorphism) has been related with obesity directly and via interaction with PUFA.
methodsWe tested the effect-modifying role of Pro12Ala on the 1 year change in obesity-related traits in a randomised clinical trial of treatment with metformin (n = 989), troglitazone (n = 363) or lifestyle modification (n = 1,004) vs placebo (n = 1,000) for diabetes prevention in high-risk individuals.
resultsAt baseline, Ala12 carriers had larger waists (p < 0.001) and, in a subset, more subcutaneous adipose tissue (SAT; lumbar 2/3; p = 0.04) than Pro12 homozygotes. There was a genotype-by-intervention interaction on 1-year weight change (p = 0.01); in the placebo arm, Pro12 homozygotes gained weight and Ala12 carriers lost weight (p = 0.001). In the metformin and lifestyle arms, weight loss occurred across genotypes, but was greatest in Ala12 carriers (p < 0.05). Troglitazone treatment induced weight gain, which tended to be greater in Ala12 carriers (p = 0.08). In the placebo group, SAT (lumbar 2/3, lumbar 4/5) decreased in Ala12 allele carriers, but was unchanged in Pro12 homozygotes (p < or = 0.005). With metformin treatment, SAT decreased independently of genotype. In the lifestyle arm, SAT (lumbar 2/3) reductions occurred across genotypes, but were greater in Ala12 carriers (p = 0.03). A genotype-by-PUFA intake interaction on reduction in visceral fat (lumbar 4/5; p = 0.04) was also observed, which was most evident with metformin treatment (p < 0.001). CONCLUSIONS/
interpretationWithin the Diabetes Prevention Program, the Ala12 allele influences central obesity, an effect which may differ by treatment group and dietary PUFA intake (ClinicalTrials.gov ID no: NCT00004992).
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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.