Prevention of diabetic ketoacidosis in relatives screened for islet autoantibodies and followed up in the TrialNet Pathway to Prevention study at a single institution in Italy
Authors' conclusion
The early identification of individuals at risk for type 1 diabetes through a single-centre approach, combining autoantibody screening and regular monitoring, completely prevented diabetes-associated ketoacidosis at disease onset in relatives of individuals with type 1 diabetes.
Study context
- Population
- First-degree (aged 1–45 years) and second-degree (aged 1–20 years) relatives of individuals with T1D screened for islet autoantibodies, San Raffaele Hospital, Milan, Italy, 2005–2020follow-up in 78.5%
- Participants
- 4,046 participants
- Exposure
- Autoantibody-negative vs single-positive vs multiple-positive relatives
- Outcome
- Progression to stage 3 T1D and incidence of DKA
Methodological detailssingle-centre, within the international multisite TrialNet Natural History Study-Pathway to Prevention
- Single-centre
- Within the international multisite TrialNet Natural History Study-Pathway to Prevention
Main finding
As reported in the abstract
median follow-up 9.9 (IQR 6.5-13.5) years
| Group | Value | Median time to onset (IQR), years | KM survival free of clinical diabetes at 15 years (95% CI) |
|---|---|---|---|
| Autoantibody-negative | 0.4% | 7.8 (5.4-10.4) | 99.5% (99.1, 99.7) |
| Single-positive | 6.5% | 7.9 (2.1-11.8) | 87.3% (74.4, 94.0) |
| Multiple-positive | 43.1% | 2.9 (0.9-6.5) | 45.9% (31.1, 59.6) |
Value
Autoantibody-negative0.4%
Single-positive6.5%
Multiple-positive43.1%
Median time to onset (IQR), years
Autoantibody-negative7.8 (5.4-10.4)
Single-positive7.9 (2.1-11.8)
Multiple-positive2.9 (0.9-6.5)
KM survival free of clinical diabetes at 15 years (95% CI)
Autoantibody-negative99.5% (99.1, 99.7)
Single-positive87.3% (74.4, 94.0)
Multiple-positive45.9% (31.1, 59.6)
- Between Autoantibody-negative and Multiple-positive: P = 0.012 — across the three groups
- Between Autoantibody-negative and Multiple-positive: P < 0.001 — across the three groups
- Progression to stage 3
- 51 (1.6%)
- DKA at disease onset
- 0
Observational data: associations, not effects.
Further findings
Autoantibody positivity at first screening
- Positive
- 4.9%
- Single autoantibody
- 3.1%
- Multiple autoantibodies
- 1.8%
Clinical status at onset · disease onset
- Median (IQR) HbA1c
- 64 (52-86) mmol/mol (8.0 [6.9-10.0]%)
- Median (IQR) venous pH
- 7.37 (7.35-7.39)
- Hospitalisation of paediatric participants (standard practice for education and insulin optimisation)
- 22
Original publication
Prevention of diabetic ketoacidosis in relatives screened for islet autoantibodies and followed up in the TrialNet Pathway to Prevention study at a single institution in Italy. Diabetologia. Published 29 May 2025. doi:10.
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