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

Yang PK, Jackson SL, Charest BR, Cheng YJ, Sun YV, Raghavan S, Litkowski EM, Legvold BT, Rhee MK, Oram RA, Kuklina EV, Vujkovic M, Reaven PD, Cho K, Leong A, Wilson PWF, Zhou J, Miller DR, Sharp SA, Staimez LR, North KE, Highland HM, Phillips LS, Million Veteran Program. Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP). Diabetes Care. 2024 Jun 1; 47(6):1032-1041.

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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.