IDAA1c cutoff of 9 or less had 45% sensitivity for T1D remission in youth with overweight or obesity

Researchers analyzing data from the SEARCH for Diabetes in Youth study reported that an insulin dose-adjusted hemoglobin A1c (IDAA1c) cutoff of 9 or less had suboptimal accuracy for identifying partial remission of type 1 diabetes (T1D) in US youth, with the weakest results in those with overweight or obesity, according to thecardiologyadvisor.com, which summarized the Diabetes Care publication endocrinologyadvisor.comthecardiologyadvisor.comendocrinologyadvisor.comOpen source ↗. The analysis included 422 patients: 299 with underweight or normal weight and 121 with overweight or obesity.

The cutoff is widely used as an accessible surrogate for stimulated C-peptide in the mixed-meal tolerance test (MMTT) to define partial remission and to assess eligibility for disease-modifying therapy trials. It was derived and validated in European cohorts, not in a US population. In this study, the reference was an MMTT-stimulated C-peptide level of 0.91 ng/mL or higher, and all participants underwent testing within 12 months of diagnosis.

IDAA1c accuracy by weight group

Median age was 12 years in both groups, and HbA1c was 6.9% and 7.0%, respectively. Median IDAA1c was higher in the overweight and obesity group than in the underweight or normal-weight group (9.28 vs 8.95), despite higher stimulated C-peptide (1.88 vs 1.25 ng/mL).

In the ROC analysis, the optimal overall cutoff was 9.2 (sensitivity 67%, specificity 77%), while the conventional cutoff of 9 or less gave a sensitivity of 61% and a specificity of 79% endocrinologyadvisor.comthecardiologyadvisor.comendocrinologyadvisor.comOpen source ↗. By group, the optimal cutoff was 9.2 in the normal-weight group (sensitivity 73%, specificity 77%) and 11.6 in the overweight and obesity group (sensitivity 93%, specificity 58%). The standard cutoff of 9 was more sensitive in the normal-weight group than in the overweight and obesity group (69% vs 45%).

Using the cutoff of 9 or less, fewer participants with overweight or obesity were classified as in remission (40% vs 52%). By stimulated C-peptide, more of them were in remission: 79% vs 64% at 0.91 ng/mL or higher, and 91% vs 81% at 0.60 ng/mL or higher.

BMI z-score and study limits

In a sensitivity analysis, combining IDAA1c with BMI z-score improved accuracy (AUC 0.85), while adding age, sex or Tanner stage did not.

The authors noted several limitations. The MMTT in SEARCH was truncated to 60–90 minutes instead of the standard 120 minutes, the design was post hoc and exploratory, the timing of the MMTT within the first year was not standardized, and there was no validation against long-term microvascular outcomes endocrinologyadvisor.comthecardiologyadvisor.comendocrinologyadvisor.comOpen source ↗. The authors concluded that IDAA1c should be used with caution as a screening test for partial remission in individuals.