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Evidence for different clinical subtypes of type 1 diabetes mellitus: a prospective study
A Schiffrin1, A Ciampi, L Hendricks
1Division of Endocrinology and Metabolism, Montreal Children's Hospital, Quebec, Canada.
Insights
In newly-diagnosed diabetic children, age, sex, and autoantibodies predict remaining beta-cell function. These factors also identify distinct disease subtypes with different rates of beta-cell loss.
Area of Science:
- Pediatric Endocrinology
- Immunology of Diabetes
- Clinical Prediction Modeling
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing beta cells.
- Predicting the rate of beta-cell loss is crucial for managing T1D and developing personalized treatment strategies.
- Understanding factors influencing disease progression in children is essential for long-term outcomes.
Purpose of the Study:
- To identify predictors of residual beta-cell function duration in newly-diagnosed diabetic children.
- To determine if these predictors can stratify patients into distinct disease subtypes.
- To analyze the impact of clinical and immunological factors on T1D progression.
Main Methods:
- A prospective cohort study of 170 newly-diagnosed diabetic children followed for 60 months.
- Assessment of clinical parameters including age, sex, and diabetic ketoacidosis (DKA) at diagnosis.
- Measurement of autoantibodies (ICAs) and C-peptide response to a Sustacal meal to evaluate beta-cell function.
Main Results:
- Age, sex, ICA presence, DKA at diagnosis, and C-peptide peak at diagnosis significantly predicted the duration of residual beta-cell function.
- C-peptide secretion at diagnosis, ICA presence, age, and sex were used to identify three prognostic groups.
- These groups exhibited varying rates of beta-cell loss over the 60-month follow-up period.
Conclusions:
- Clinical and immunological factors at diagnosis are significant predictors of beta-cell function duration in pediatric T1D.
- These predictors enable the identification of distinct prognostic subgroups, aiding in personalized disease management.
- Early identification of these subtypes can inform therapeutic interventions and improve long-term T1D outcomes in children.
Abstract:
The purpose of this study was to determine whether the sex, age, severity of clinical presentation, presence of ICAs, IAs, and HLA-DR and DQ types could predict, in a cohort of newly-diagnosed diabetic children: (1) the duration of beta-cell function as measured by C-peptide response to a Sustacal meal; and (2) determine if those predictors could identify disease subtypes. A cohort of 170 consecutive patients was followed for 60 months after diagnosis. We found that age (0.0029), sex (0.0136), ICA (0.0001), presence of DKA (0.0070) and C-peptide peak at diagnosis (0.0000) significantly predicted the duration of residual beta-cell function over time. Furthermore, C-peptide secretion at diagnosis, presence of ICA, age and sex allowed the identification of three different prognostic groups with varying acceleration of beta-cell loss.