{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:46:07Z","timestamp":1778672767487,"version":"3.51.4"},"reference-count":38,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>The metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>We used data from 356 youth (mean age 16.7 years; 50% female) in the Exploring Perinatal Outcomes Among Children (EPOCH) cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-h glucose, HOMA of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, BMI z score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z score, in utero exposure to maternal diabetes, and ethnicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Higher weighted GRS was associated with lower oral disposition index (\u03b2 = \u22120.11; 95% CI \u22120.19, \u22120.02) and insulinogenic index (\u03b2 = \u22120.08; 95% CI \u22120.17, \u22120.001), but not with fasting glucose (\u03b2 = 0.01; 95% CI \u22120.01, 0.02), 2-h glucose (\u03b2 = 0.03; 95% CI \u22120.0004, 0.06), or HOMA-IR (\u03b2 = 0.02; 95% CI \u22120.04, 0.07). BMI z score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Our results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk of T2D.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc21-0464","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T15:30:11Z","timestamp":1626190211000},"page":"2018-2024","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study"],"prefix":"10.2337","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-8868","authenticated-orcid":false,"given":"Maggie A.","family":"Stanislawski","sequence":"first","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Litkowski","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"},{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO"},{"name":"Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0643-4873","authenticated-orcid":false,"given":"Sridharan","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"},{"name":"Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO"},{"name":"Division of Hospital Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie K.","family":"Harrall","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO"},{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah H.","family":"Glueck","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO"},{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan M.","family":"Lange","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"},{"name":"Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9514-8929","authenticated-orcid":false,"given":"Dana","family":"Dabelea","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO"},{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, CO"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie A.","family":"Lange","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO"},{"name":"Department of Epidemiology, University of Colorado School of Public Health, Aurora, 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