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Partial remission definition: validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish children
Marie Louise C Max Andersen1, Philip Hougaard, Sven Pörksen
1Department of Pediatrics, Herlev Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Insights
The insulin dose-adjusted HbA1c (IDAA1c) definition effectively identifies partial remission (PR) in type 1 diabetes (T1D). While IDAA1c maintains diagnostic and prognostic value, specificity may vary with cohort-specific C-peptide stimulation levels.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Diabetes Research
Background:
- Partial remission (PR) is crucial for managing type 1 diabetes (T1D) in children, preserving residual beta-cell function.
- The insulin dose-adjusted HbA1c (IDAA1c) metric offers a potential tool for defining PR, simplifying clinical assessment.
- Validating IDAA1c against established markers like stimulated C-peptide (SCP) is essential for its clinical utility.
Purpose of the Study:
- To validate the diagnostic and prognostic accuracy of the IDAA1c definition for partial remission in pediatric type 1 diabetes.
- To assess the predictive value of IDAA1c, in conjunction with patient age, for maintaining C-peptide secretion.
Main Methods:
- The IDAA1c metric was developed using data from the European Hvidoere cohort (n=251).
- Validation was performed in a separate Danish cohort (n=129) followed from T1D onset.
- Receiver operating characteristic (ROC) curve analysis evaluated the predictive performance of IDAA1c and age for partial C-peptide remission (SCP > 300 pmol/L).
Main Results:
- PR rates defined by IDAA1c ≤ 9 were comparable between the Danish and Hvidoere cohorts at 3, 6, 9, and 12 months.
- IDAA1c combined with age significantly improved predictive accuracy (AUC 0.94 at 6 months, 0.90 at 12 months) compared to age alone.
- The sensitivity and specificity of IDAA1c for PR varied, with higher specificity observed in the Hvidoere cohort.
Conclusions:
- The IDAA1c measure retains significant diagnostic and prognostic power for partial remission in pediatric T1D.
- Cohort-specific differences in C-peptide stimulation levels can influence the specificity of IDAA1c when using fixed thresholds.
- Further refinement of IDAA1c criteria may be necessary to account for inter-cohort variability in beta-cell response.
Objective:
To validate the partial remission (PR) definition based on insulin dose-adjusted HbA1c (IDAA1c).
Subjects And Methods:
The IDAA1c was developed using data in 251 children from the European Hvidoere cohort. For validation, 129 children from a Danish cohort were followed from the onset of type 1 diabetes (T1D). Receiver operating characteristic curve (ROC) analysis was used to evaluate the predictive value of IDAA1c and age on partial C-peptide remission (stimulated C-peptide, SCP > 300 pmol/L).
Results:
PR (IDAA1c ≤ 9) in the Danish and Hvidoere cohorts occurred in 62 vs. 61% (3 months, p = 0.80), 47 vs. 44% (6 months, p = 0.57), 26 vs. 32% (9 months, p = 0.32) and 19 vs. 18% (12 months, p = 0.69). The effect of age on SCP was significantly higher in the Danish cohort compared with the Hvidoere cohort (p < 0.0001), likely due to higher attained Boost SCP, so the sensitivity and specificity of those in PR by IDAA1c ≤ 9, SCP > 300 pmol/L was 0.85 and 0.62 at 6 months and 0.62 vs. 0.38 at 12 months, respectively. IDAA1c with age significantly improved the ROC analyses and the AUC reached 0.89 ± 0.04 (age) vs. 0.94 ± 0.02 (age + IDAA1c) at 6 months (p < 0.0004) and 0.76 ± 0.04 (age) vs. 0.90 ± 0.03 (age + IDAA1c) at 12 months (p < 0.0001).
Conclusions:
The diagnostic and prognostic power of the IDAA1c measure is kept but due to the higher Boost stimulation in the Danish cohort, the specificity of the formula is lower with the chosen limits for SCP (300 pmol/L) and IDAA1c ≤9, respectively.
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