Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP)
Peter K. Yang, Sandra L. Jackson, Brian R. Charest, Yiling J. Cheng, Yan V. Sun, Sridharan Raghavan, Elizabeth M. Litkowski, Brian T. Legvold, Mary K. Rhee, Richard A. Oram, Elena V. Kuklina, Marijana Vujkovic, Peter D. Reaven, Kelly Cho, Aaron Leong, Peter W.F. Wilson, Jin Zhou, Donald R. Miller, Seth A. Sharp, Lisa R. Staimez, Kari E. North, Heather M. Highland, Lawrence S. Phillips, Sumitra Muralidhar, Jennifer Moser, Jennifer E. Deen, J. Michael Gaziano, Jean Beckham, Kyong-Mi Chang, Philip S. Tsao, Shiuh-Wen Luoh, Juan P. Casas, Lori Churby, Stacey B. Whitbourne, Jessica V. Brewer, Mary T. Brophy, Luis E. Selva, Shahpoor (Alex) Shayan, Kelly Cho, Saiju Pyarajan, Scott L. DuVall, Todd Connor, Dean P. Argyres, Brady Stephens, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Jeffrey Whittle, Frank Jacono, Jean Beckham, John Wells, Salvador Gutierrez, Kathrina Alexander, Kimberly Hammer, James Norton, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, River Smith, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Ana Palacio, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Peter Liang, Daryl Fujii, Patrick Strollo, Edward Boyko, Jessica Walsh, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Prakash Balasubramanian,- Advanced and Specialized Nursing
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
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 they resembled 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 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 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.