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

Journal Article · · Diabetes Care
DOI: https://doi.org/10.2337/dc23-1927 · OSTI ID:2336852
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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.

Sponsoring Organization:
USDOE
OSTI ID:
2336852
Journal Information:
Diabetes Care, Journal Name: Diabetes Care Journal Issue: 6 Vol. 47; ISSN 0149-5992
Publisher:
American Diabetes AssociationCopyright Statement
Country of Publication:
United States
Language:
English

References (23)

Adult-Onset Type 1 Diabetes: Current Understanding and Challenges journal October 2021
Two Single Nucleotide Polymorphisms Identify the Highest-Risk Diabetes HLA Genotype journal November 2008
Million Veteran Program: A mega-biobank to study genetic influences on health and disease journal February 2016
Initiation of Continuous Glucose Monitoring Is Linked to Improved Glycemic Control and Fewer Clinical Events in Type 1 and Type 2 Diabetes in the Veterans Health Administration journal February 2023
Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes journal December 2019
Genetic Risk Scores journal November 2019
Levels of C-peptide, body mass index and age, and their usefulness in classification of diabetes in relation to autoimmunity, in adults with newly diagnosed diabetes in Kronoberg, Sweden journal June 2012
Age‐dependent decline of β‐cell function in type 1 diabetes after diagnosis: a multi‐centre longitudinal study journal October 2013
Next-generation genotype imputation service and methods journal August 2016
A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults journal November 2015
Random plasma glucose predicts the diagnosis of diabetes journal July 2019
Type 1 diabetes mellitus journal March 2017
Misdiagnosis and Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes: Patient and Caregiver Perspectives journal July 2019
Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes journal April 2019
Automated Detection and Classification of Type 1 Versus Type 2 Diabetes Using Electronic Health Record Data journal March 2013
A Type 1 Diabetes Genetic Risk Score Can Identify Patients With GAD65 Autoantibody–Positive Type 2 Diabetes Who Rapidly Progress to Insulin Therapy journal October 2018
7. Diabetes Technology: Standards of Medical Care in Diabetes—2022 journal December 2021
Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies journal October 2019
Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank journal February 2018
Weighing in on Type 2 Diabetes in the Military journal November 2001
Estimating GFR Using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation: More Accurate GFR Estimates, Lower CKD Prevalence Estimates, and Better Risk Predictions journal April 2010
Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score journal January 2019
Utility of Diabetes Type–Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth journal March 2022