{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:39:03Z","timestamp":1778546343877,"version":"3.51.4"},"reference-count":30,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01 DK048489"],"award-info":[{"award-number":["U01 DK048489"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK072041-12"],"award-info":[{"award-number":["R01 DK072041-12"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32GM007748-36"],"award-info":[{"award-number":["5T32GM007748-36"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2T32DK007028-41"],"award-info":[{"award-number":["2T32DK007028-41"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>There is substantial heterogeneity in insulin sensitivity, and genetics may suggest possible mechanisms by which common variants influence this trait.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>In 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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/js.2019-00069","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T16:58:54Z","timestamp":1561395534000},"page":"1663-1677","source":"Crossref","is-referenced-by-count":12,"title":["A Polygenic Lipodystrophy Genetic Risk Score Characterizes Risk Independent of BMI in the Diabetes Prevention Program"],"prefix":"10.1210","volume":"3","author":[{"given":"Shylaja","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of California at San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A","family":"Jablonski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C","family":"Knowler","sequence":"additional","affiliation":[{"name":"Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Dagogo-Jack","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"E. 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Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-France","family":"Hivert","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Health System, Miami, Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard & Massachusetts 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