2026-10-11T22:37:10Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33570751 2026-09-29T14:42:45Z category_27241 portal_785 item_type_1 month_year_09_2026

Insulin Dose-Adjusted Hemoglobin A1c has Suboptimal Performance for Identifying C-peptide-defined Partial Remission: The SEARCH for Diabetes in Youth Study Michael L Ferm (24764780) Xiaofan Huang (657238) Charles G Minard (23840281) Daniel J DeSalvo (24764783) Amy S Shah (17691909) Catherine Pihoker (8981865) Anna C Bellatorre (24764788) Maria J Redondo (24129603) Other health sciences not elsewhere classified Honeymoon Period Remission Type 1 Diabetes Children Beta Cell Function C-Peptide Obesity <p dir="ltr">Objective: Insulin Dose-Adjusted Hemoglobin A1c (IDAA1c = HbA1c (%) + (4 * Total Daily Dose in units/kg/day) ≤9 is widely used to define partial remission in pediatric type 1 diabetes and as an eligibility criterion or outcome in disease modifying therapy trials. However, it has not been validated in U.S. youth. Because higher BMI increases insulin resistance and insulin requirements, we hypothesized that IDAA1c would perform suboptimally in participants with overweight/obesity. Research Design and Methods: We analyzed data from 422 SEARCH for Diabetes in Youth study participants with mixed-meal tolerance test (MMTT)-stimulated C-peptide within 12 months of diagnosis. Partial remission was defined using MMTT-stimulated area under the curve (AUC) mean C-peptide. Participant characteristics were compared by BMI category (<85th percentile [normal/underweight] and ≥85th percentile [overweight/obese]) using Wilcoxon rank-sum and Fisher’s exact tests. Sensitivity, specificity and receiver operating characteristic (ROC) AUC of IDAA1c ≤9 for identifying partial remission were evaluated. Results: Normal/underweight participants, versus overweight/obese participants, had lower IDAA1c (8.95 vs 9.28, p=0.043) despite lower stimulated C-peptide (1.25 vs 1.88 ng/mL, p<0.001). Overall, IDAA1c ≤9 had 61% sensitivity and 79% specificity for predicting C-peptide ≥0.91 ng/mL with ROC AUC=0.77. Among overweight/obese participants, sensitivity was 45% and specificity 81%. A Youden index-derived cutoff of IDAA1c ≤11.6 improved sensitivity to 93%, with specificity of 54% in overweight/obese participants. Conclusions: IDAA1c ≤9 demonstrated suboptimal accuracy as a screening test for partial remission, especially underestimating β-cell function in youth with overweight/obesity. BMI-specific cutoffs improved sensitivity but reduced specificity.</p> 2026-09-29T14:42:45Z Image Figure 10.2337/figshare.33570751.v1 https://figshare.com/articles/figure/Insulin_Dose-Adjusted_Hemoglobin_A1c_has_Suboptimal_Performance_for_Identifying_C-peptide-defined_Partial_Remission_The_SEARCH_for_Diabetes_in_Youth_Study/33570751 CC BY-NC-SA 4.0