Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP)
Author:
Yang Peter K.123ORCID, Jackson Sandra L.1, Charest Brian R.4, Cheng Yiling J.5, Sun Yan V.26, Raghavan Sridharan78, Litkowski Elizabeth M.78, Legvold Brian T.9, Rhee Mary K.29, Oram Richard A.10, Kuklina Elena V.1, Vujkovic Marijana11, Reaven Peter D.12, Cho Kelly413, Leong Aaron141516, Wilson Peter W.F.2610, Zhou Jin1217, Miller Donald R.18, Sharp Seth A.19, Staimez Lisa R.6, North Kari E.3, Highland Heather M.3, Phillips Lawrence S.29ORCID, , Muralidhar Sumitra, Moser Jennifer, Deen Jennifer E., Gaziano J. Michael, Beckham Jean, Chang Kyong-Mi, Tsao Philip S., Luoh Shiuh-Wen, Casas Juan P., Churby Lori, Whitbourne Stacey B., Brewer Jessica V., Brophy Mary T., Selva Luis E., Shayan Shahpoor (Alex), Cho Kelly, Pyarajan Saiju, DuVall Scott L., Connor Todd, Argyres Dean P., Stephens Brady, Wilson Peter, McArdle Rachel, Dellitalia Louis, Mattocks Kristin, Harley John, Whittle Jeffrey, Jacono Frank, Beckham Jean, Wells John, Gutierrez Salvador, Alexander Kathrina, Hammer Kimberly, Norton James, Villareal Gerardo, Kinlay Scott, Xu Junzhe, Hamner Mark, Mathew Roy, Bhushan Sujata, Iruvanti Pran, Godschalk Michael, Ballas Zuhair, Smith River, Mastorides Stephen, Moorman Jonathan, Gappy Saib, Klein Jon, Ratcliffe Nora, Palacio Ana, Okusaga Olaoluwa, Murdoch Maureen, Sriram Peruvemba, Yeh Shing Shing, Tandon Neeraj, Jhala Darshana, Aguayo Samuel, Cohen David, Sharma Satish, Liangpunsakul Suthat, Oursler Kris Ann, Whooley Mary, Ahuja Sunil, Constans Joseph, Meyer Paul, Greco Jennifer, Rauchman Michael, Servatius Richard, Gaddy Melinda, Wallbom Agnes, Morgan Timothy, Stapley Todd, Liang Peter, Fujii Daryl, Strollo Patrick, Boyko Edward, Walsh Jessica, Gupta Samir, Huq Mostaqul, Fayad Joseph, Hung Adriana, Lichy Jack, Hurley Robin, Robey Brooks, Balasubramanian Prakash
Affiliation:
1. 1Division for Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 2. 2Atlanta Veterans Administration Medical Center, Atlanta, GA 3. 3Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 4. 4Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA 5. 5Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 6. 6Rollins School of Public Health, Emory University, Atlanta, GA 7. 7Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO 8. 8University of Colorado School of Medicine, Denver, CO 9. 9Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, GA 10. 10College of Medicine and Health, University of Exeter Medical School, Devon, U.K 11. 11Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 12. 12Phoenix Veterans Affairs Health Care System, Phoenix, AZ 13. 13Brigham and Women’s Hospital, Boston, MA 14. 14Harvard Medical School, Boston, MA 15. 15Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA 16. 16Diabetes Unit, Endocrine Division, Massachusetts General Hospital, Boston, MA 17. 17UCLA Department of Medicine, University of California, Los Angeles, CA 18. 18Bedford Veterans Affairs Medical Center, Bedford, MA 19. 19Division of Endocrinology and Diabetes, Stanford University, Palo Alto, CA
Abstract
OBJECTIVE
To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates.
RESEARCH DESIGN AND METHODS
Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011–2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%).
RESULTS
T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001.
CONCLUSIONS
Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.
Funder
Diabetes UK U.S. Department of Veterans Affairs Oak Ridge Institute for Science and Education the Million Veteran Program, Office of Research and Development, Veterans Health Administration National Heart, Lung, and Blood Institute National Institutes of Health Doris Duke Charitable Foundation National Center for Advancing Translational Sciences Cystic Fibrosis Foundation Boettcher Foundation
Publisher
American Diabetes Association
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