Trial reportThe Journal of clinical endocrinology and metabolism2009
The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program.
Trial report in The Journal of clinical endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 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, 3 syntheses or guidelines pooled it, 51 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
- Pooled it
- The pharmacogenetics of type 2 diabetes: a systematic review.Diabetes care · 2014Pooled it
- Impact of individual and environmental factors on dietary or lifestyle interventions to prevent type 2 diabetes development: a systematic review.Communications medicine · 2023Article
- Pharmacogenomics and Personalized Medicine in Type 2 Diabetes Mellitus: Potential Implications for Clinical Practice.Pharmacogenomics and personalized medicine · 2021Review
- A review of clinical pharmacogenetics Studies in African populations.Personalized medicine · 2020Review
- Physical activity, sedentary behaviors and the incidence of type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis (MESA).BMJ open diabetes research & care · 2016Article
- Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.African health sciences · 2015Article
- The Challenges and Opportunities Associated with Reimbursement for Obesity Pharmacotherapy in the USA.PharmacoEconomics · 2015Review
- Impact of ENPP1 K121Q on change of insulin resistance after web-based intervention in Korean men with diabetes and impaired fasting glucose.Journal of Korean medical science · 2014Article
- Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.PLoS medicine · 2014Article
- Susceptibility to type 2 diabetes mellitus--from genes to prevention.Nature reviews. Endocrinology · 2014Review
- Inputs and outputs of insulin receptor.Protein & cell · 2014Review
- Connexin36 contributes to INS-1E cells survival through modulation of cytokine-induced oxidative stress, ER stress and AMPK activity.Cell death and differentiation · 2013Article
- Gene-environment and gene-treatment interactions in type 2 diabetes: progress, pitfalls, and prospects.Diabetes care · 2013Review
- Variants of insulin-signaling inhibitor genes in type 2 diabetes and related metabolic abnormalities.International journal of genomics · 2013Article
- Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program.Arteriosclerosis, thrombosis, and vascular biology · 2012Review
- The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview.Scientifica · 2012Review
- ENPP1/PC-1 K121Q and other predictors of posttransplant diabetes.Metabolic syndrome and related disorders · 2011Article
- The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention.Diabetologia · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 1 country.
Funding
Abstract
contextInsulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q (rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes. OBJECTIVE AND
interventionWe examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs. placebo in the Diabetes Prevention Program (DPP). DESIGN, SETTING, PARTICIPANTS, AND OUTCOME: We genotyped ENPP1 K121Q in 3548 DPP participants and performed Cox regression analyses using genotype, intervention, and interactions as predictors of diabetes incidence.
resultsFasting glucose and glycated hemoglobin were higher in QQ homozygotes at baseline (P < 0.001 for both). There was a significant interaction between genotype at rs1044498 and intervention under the dominant model (P = 0.03). In analyses stratified by treatment arm, a positive association with diabetes incidence was found in Q allele carriers compared to KK homozygotes [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.08-1.76; P = 0.009] in the placebo arm (n = 996). Lifestyle modification eliminated this increased risk. These findings persisted after adjustment for body mass index and race/ethnicity. Association of ENPP1 K121Q genotype with diabetes incidence under the additive and recessive genetic models showed consistent trends [HR, 1.10 (95% CI, 0.99-1.23), P = 0.08; and HR, 1.16 (95% CI, 0.92-1.45), P = 0.20, respectively] but did not reach statistical significance.
conclusionsENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk.
Indexed as
Identifiers
What OpenQuestion holds
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.