Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes

The Million Veteran Program (MVP)

  • Yang, Peter K.
  • Jackson, Sandra L.
  • Charest, Brian R.
  • Cheng, Yiling J.
  • Sun, Yan V.
  • Raghavan, Sridharan
  • Litkowski, Elizabeth M.
  • Legvold, Brian T.
  • Rhee, Mary K.
  • Oram, Richard A.
  • Kuklina, Elena V.
  • Vujkovic, Marijana
  • Reaven, Peter D.
  • Cho, Kelly
  • Leong, Aaron
  • Wilson, Peter W.F.
  • Zhou, Jin
  • Miller, Donald R.
  • Sharp, Seth A.
  • Staimez, Lisa R.
  • North, Kari E.
  • Highland, Heather M.
  • Phillips, Lawrence S.
  • 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
Diabetes Care 47(6):p 1032-1041, June 2024. | DOI: 10.2337/dc23-1927

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.

Copyright © 2024 by the American Diabetes Association, Inc.
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