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Updated: May 2, 2026
Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Natural history of a pediatric cohort with islet autoantibody positivity: a single-center retrospective cohort study
Emilio Casalini1, Donella Puliti2, Barbara Piccini1
1Diabetology Unit, Meyer Children's Hospital IRCCS, Florence 50139, Italy.
Insights
Persistent anti-β-cell antibodies (AABs) predict type 1 diabetes (T1D) progression. Early identification via AAB monitoring in children can prevent diabetic ketoacidosis (DKA) at diagnosis.
Area of Science:
- Endocrinology
- Immunology
- Metabolic Diseases
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells.
- Anti-beta-cell antibodies (AABs) are key biomarkers for identifying individuals at risk of T1D.
- Understanding the natural history of AAB-positive individuals is crucial for early intervention and prevention strategies.
Purpose of the Study:
- To describe the natural history of patients with at least one positive AAB.
- To analyze the progression to stage 3 T1D and the clinical severity at diagnosis in this cohort.
- To identify risk factors associated with T1D progression.
Main Methods:
- A single-center retrospective cohort study was conducted from February 2012 to April 2025.
- One hundred and six patients with at least one positive AAB were enrolled in a structured follow-up program.
- Progression to stage 3 T1D and the occurrence of diabetic ketoacidosis (DKA) at diagnosis were the main outcome measures.
Main Results:
- During a median follow-up of 4 years, 19 out of 106 AAB-positive patients progressed to stage 3 T1D; none presented with DKA at diagnosis.
- The 5-year cumulative risk of progression was 16.6%.
- Multiple AAB positivity (40.4% vs 8.3%) and glutamic acid decarboxylase (GAD) autoantibody positivity (25.7% vs 2.8%) were significantly associated with a higher 5-year risk of T1D progression.
Conclusions:
- Persistent AAB positivity, especially for GAD autoantibodies, strongly predicts progression to stage 3 T1D.
- Children identified through AAB monitoring exhibit a milder clinical presentation at diagnosis, with no DKA cases.
- These findings support AAB screening and structured follow-up programs to prevent DKA and identify candidates for disease-modifying interventions.
Context:
Type 1 diabetes (T1D) progresses from genetic risk to metabolic disease. Anti-β-cell antibodies (AABs), alongside clinical features, define the stages of T1D and enable identification of presymptomatic individuals.
Objective:
To describe the natural history of patients with ≥1 positive AAB, analyzing progression to stage 3 T1D and clinical severity at diagnosis.
Design:
Single-center retrospective cohort study (February 2012-April 2025).
Patients:
One-hundred and six patients with ≥1 AAB-positive enrolled in a structured follow-up program.
Main Outcome Measure:
progression to stage 3 T1D and occurrence of diabetic ketoacidosis (DKA) at diagnosis.
Results:
During a median follow-up of 4 years, 19 of 106 AAB-positive patients progressed to stage 3 T1D, none of whom presented with DKA at diagnosis. The 5-year cumulative risk of progression was 16.6% (95% CI: 10.0%-26.9%). Patients with multiple AAB positivity at baseline had a significantly higher 5-year risk than those with a single positive AAB (40.4% vs 8.3%; P = .0002). Glutamic acid decarboxylase (GAD) autoantibody positivity was associated with an increased 5-year risk of progression (25.7% vs 2.8% in GAD-negative children; P = .0063) and remained independently associated with T1D onset in multivariable analysis.
Conclusion:
Persistent autoantibody positivity, particularly for GAD, is strongly associated with progression to stage 3 T1D. Children identified through AAB monitoring show a milder clinical presentation at diagnosis, with no cases of DKA. These data support screening and structured follow-up of at-risk children, which may help prevent DKA and facilitate identification of candidates for disease-modifying interventions.
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