IA-2A positivity increases risk of progression within and across established stages of type 1 diabetes
Authors' conclusion
IA-2A positivity is consistently associated with increased progression risk throughout the natural history of type 1 diabetes development. Individuals with single-autoantibody positivity for IA-2A have a greater risk of disease progression than those who meet stage 1 criteria but who are IA-2A-. Approaches to incorporate IA-2A+ status into monitoring strategies for autoantibody-positive individuals should be considered.
Study context
- Population
- Adult and paediatric relatives of individuals with T1D, autoantibody-negative and autoantibody-positive, TrialNet Pathway to Prevention Studyautoantibody-negative 192 · autoantibody-positive 4,577
- Comparison
- IA-2A+ vs IA-2A- individuals within and across T1D stages
- Primary endpoint
- Cumulative incidence of clinical diabetes by autoantibody profiles and disease stages
- Follow-up
- 5 year
Methodological detailslongitudinal, Cox regression
- Longitudinal
- Cox regression
Primary result
As reported in the abstract
Single-autoantibody-positive: increased 5 year risk with IA-2A+
5.3-fold
Stage 1: increased 5 year risk with IA-2A+
2.2-fold
Stage 2: increased 5 year risk with IA-2A+
1.3-fold
Further findings
Progression risk within single-IA-2A+ category, by subgroup
| HR (95% CI) | P value | ||
|---|---|---|---|
| Children | 14.2 (1.9–103.1) | P = 0.009 | |
| IA-2A titres above the median | 3.5 (1.9–6.6) | P < 0.001 | |
| High genetic risk scores | 1.4 (1.2,1.6) | P < 0.001 | |
| HLA DR4-positive | 3.7 (1.6–8.3) | P = 0.002 | |
| 0.050.21520Hazard ratio (log scale) |
Single-IA-2A+ vs autoantibody negative, other single autoantibody, and IA-2A- stage 1
- Single-IA-2A+ showed increased metabolic dysfunction and diabetes progression
All autoantibody-positive: euglycaemic IA-2A+ vs dysglycaemic IA-2A-
- Progression risk was similar
Original publication
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