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Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP).

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Collaborators (85)

Author information

Affiliations

  • 1. Division for Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.
      Authors
    • Yang PK 1, 4, 14
    • Jackson SL 1
    • Kuklina EV 1
    (3 authors)
  • 2. Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA.
      Authors
    • Charest BR 2
    • Cho K 2
    (2 authors)
  • 3. Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.
      Authors
    • Cheng YJ 3
    (1 author)
  • 4. Atlanta Veterans Administration Medical Center, Atlanta, GA.
      Authors
    • Yang PK 1, 4, 14
    • Sun YV 4, 13
    • Rhee MK 4, 6
    • Wilson PWF 4, 7, 13
    • Phillips LS 4, 6
    (5 authors)
  • 5. Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO.
      Authors
    • Raghavan S 5
    • Litkowski EM 5
    (2 authors)
    • Show all (14)

ORCIDs linked to this article

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Diabetes Care, 01 Jun 2024, 47(6):1032-1041
https://doi.org/10.2337/dc23-1927 PMID: 38608262 

Free full text available after 01 Jun 2025

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.

Full text links 

Read article at publisher's site: https://doi.org/10.2337/dc23-1927

References 

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Funding 

Funders who supported this work.

BLRD VA (3)

Boettcher Foundation (1)

CSRD VA (3)

Cystic Fibrosis Foundation (1)

Diabetes UK (1)

Doris Duke Charitable Foundation (1)

NCATS NIH HHS (2)

NHGRI NIH HHS (1)

NHLBI NIH HHS (1)

NIAID NIH HHS (1)

NIDDK NIH HHS (4)

NIH HHS (1)

National Center for Advancing Translational Sciences (1)

National Heart, Lung, and Blood Institute (1)

National Institutes of Health (5)

Oak Ridge Institute for Science and Education

    U.S. Department of Veterans Affairs (5)

    the Million Veteran Program, Office of Research and Development, Veterans Health Administration