The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult-onset type 1 diabetes
Authors' conclusion
The inclusion of non-autoimmune diabetes is the most likely explanation for the observed lower rate of autoantibody positivity in clinician-diagnosed adult-onset type 1 diabetes. Our data support the utility of islet autoantibody measurement in clinician-suspected adult-onset type 1 diabetes in routine clinical practice.
Study context
- Population
- Individuals with clinician-diagnosed T1D at diagnosis (1112 adult-onset, 702 childhood-onset); GADA, IA-2 and ZnT8 autoantibodies and 30 T1D-associated variants genotyped1,814 T1D + 1924 T2D
- Exposure
- Autoantibody-negative vs autoantibody-positive clinician-diagnosed T1D, adult-onset and childhood-onset; T2D as non-autoimmune controls
- Type 2 diabetesn = 1,924
- Outcome
- T1D genetic risk score (T1DGRS) by autoantibody status
- Follow-up
- At diagnosis
Main finding
As reported in the abstract
Autoantibody-negative childhood-onset
0.274
mean · SD 0.034
Autoantibody-positive childhood-onset
0.277
mean · SD 0.026
Autoantibody-negative adult-onset
0.243
mean · SD 0.036
Autoantibody-positive adult-onset
0.271
mean · SD 0.026
Type 2 diabetes
0.229
mean · SD 0.034
Autoantibody-negative childhood-onset vs Autoantibody-positive childhood-onset: P = 0.4 · Autoantibody-negative adult-onset vs Autoantibody-positive adult-onset: P < 0.0001 · Autoantibody-negative adult-onset vs Type 2 diabetes: P < 0.0001
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| HLA and non-HLA genetic risk, adultsAutoantibody-negative adult-onset vs Autoantibody-positive adult-onset · protective HLA DR15-DQ6: 15% vs 3% | P < 0.0001 |
| HLA and non-HLA genetic risk, adultsAutoantibody-negative adult-onset vs Autoantibody-positive adult-onset · high-risk HLA DR3-DQ2/DR4-DQ8: 6% vs 19% | P < 0.0001 |
| HLA and non-HLA genetic risk, adultsAutoantibody-negative adult-onset vs Autoantibody-positive adult-onset · lower non-HLA T1DGRS in autoantibody-negative adults | P < 0.0001 |
| Clinical features, adultsAutoantibody-negative adult-onset vs Autoantibody-positive adult-onset | P < 0.0001 |
| Autoantibody positivity after adjustment for estimated non-autoimmune diabetesAutoantibody-positive adult-onset vs Autoantibody-positive childhood-onset · prevalence 93% (adults) vs 91% (children); similar | P = 0.4 |
- Clinical features, adults: male 75% vs 59%; BMI 27 vs 24 kg/m²; other autoimmune conditions 2% vs 10% (all p<0.0001)
Number of autoantibodies and T1D genetic risk
- Genetic risk unaffected by number of autoantibodies in adults and children
- P > 0.3
Misclassified non-autoimmune diabetes among autoantibody-negative adults
- Misclassified adults with monogenic diabetes identified
- 7
- Estimated share of autoantibody-negative adults with non-autoimmune diabetes
- 67% (95% CI 61%, 73%)
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →