ArticleJournal of the Endocrine Society2019
A Polygenic Lipodystrophy Genetic Risk Score Characterizes Risk Independent of BMI in the Diabetes Prevention Program.
Article in Journal of the Endocrine Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population.Acta diabetologica · 2024Article
- Do gene-environment interactions have implications for the precision prevention of type 2 diabetes?Diabetologia · 2022Review
- Lipodystrophy for the Diabetologist-What to Look For.Current diabetes reports · 2022Review
- Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots.Nature communications · 2022Article
- Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract.Frontiers in pediatrics · 2022Article
- Genetic susceptibility, obesity and lifetime risk of type 2 diabetes: The ARIC study and Rotterdam Study.Diabetic medicine : a journal of the British Diabetic Association · 2021Article
- Genetics of Type 2 Diabetes: Opportunities for Precision Medicine: JACC Focus Seminar.Journal of the American College of Cardiology · 2021Review
- Identification and Potential Clinical Utility of theFrontiers in genetics · 2020Article
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Authors and funding
15 authors at 11 institutions in 1 country.
Funding
Abstract
contextThere is substantial heterogeneity in insulin sensitivity, and genetics may suggest possible mechanisms by which common variants influence this trait.
objectivesWe aimed to evaluate an 11-variant polygenic lipodystrophy genetic risk score (GRS) for association with anthropometric, glycemic and metabolic traits in the Diabetes Prevention Program (DPP). In secondary analyses, we tested the association of the GRS with cardiovascular risk factors in the DPP.
designIn 2713 DPP participants, we evaluated a validated GRS of 11 common variants associated with fasting insulin-based measures of insulin sensitivity discovered through genome-wide association studies that cluster with a metabolic profile of lipodystrophy, conferring high metabolic risk despite low body mass index (BMI).
resultsAt baseline, a higher polygenic lipodystrophy GRS was associated with lower weight, BMI, and waist circumference measurements, but with worse insulin sensitivity index (ISI) values. Despite starting at a lower weight and BMI, a higher GRS was associated with less weight and BMI reduction at one year and less improvement in ISI after adjusting for baseline values but was not associated with diabetes incidence. A higher GRS was also associated with more atherogenic low-density lipoprotein peak-particle-density at baseline but was not associated with coronary artery calcium scores in the Diabetes Prevention Program Outcomes Study.
conclusionsIn the DPP, a higher polygenic lipodystrophy GRS for insulin resistance with lower BMI was associated with diminished improvement in insulin sensitivity and potential higher cardiovascular disease risk. This GRS helps characterize insulin resistance in a cohort of individuals at high risk for diabetes, independent of adiposity.
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