Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes
Authors' conclusion
Autoantibody-positive individuals who lack both high-risk HLA haplotypes (DRX/DRX) or have HLA-DR3-DQ2 but lack HLA-DR4-DQ8 (DR3/non-DR4) have phenotypic differences compared with DR3/DR4 and DR4/non-DR3 individuals, suggesting that there is aetiological heterogeneity in type 1 diabetes.
Study context
- Population
- Islet autoantibody-positive relatives of individuals with T1D
- Participants
- 1,263 / 2,340 / 1,607 / 1,294
- Exposure
- Autoantibody-positive relatives grouped by HLA haplotype: DRX/DRX vs DR3/DR4, DR4/non-DR3 and DR3/non-DR4
- DR3/DR4n = 1,263
- DR4/non-DR3n = 2,340
- DR3/non-DR4n = 1,607
- DRX/DRXn = 1,294reference
- Outcome
- IA-2A prevalence at enrolment
- Follow-up
- Enrolment
Main finding
As reported in the abstract
DRX/DRX vs DR4/non-DR3: P < 0.001 · DRX/DRX vs DR3/DR4: P < 0.001
Observational data: associations, not effects.
Further findings
IAA prevalence at enrolment
- IAA prevalence at enrolment — IAA% similar in DRX/DRX, DR4/non-DR3 and DR3/DR4, lower in DR3/non-DR4
- p<0.001
Demographic and metabolic characteristics
- DRX/DRX vs DR3/DR4: older, fewer White, more overweight/obesity, higher preserved C-peptide (lower Index60)
- all p<0.005
- DRX/DRX vs DR3/non-DR4: younger, more Hispanic, lower Index60
- all p<0.005
- DRX/DRX vs DR4/non-DR3: fewer White or non-Hispanic, lower Index60
Progressors to clinical T1D
- Participants who progressed to clinical T1D
- 1292
- DR3/non-DR4: higher GADA%, lower IA-2A% and lower IAA% than other groups
- all p<0.01
- DR3/DR4: youngest age at diagnosis
- all p<0.001
Original publication
Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes. Diabetologia. Published 13 December 2024. doi:10.
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