Laura M Jacobsen, Brian N Bundy, Heba M Ismail, Mark Clements, Megan Warnock, Susan Geyer, Desmond A Schatz, Jay M Sosenko
The Journal of Clinical Endocrinology & Metabolism, First published online July 26, 2022, dgac440
https://doi.org/10.1210/clinem/dgac440
HbA1c from ≥ 5.7% to < 6.5% (39-46 mmol/mol) indicates prediabetes according to American Diabetes Association guidelines, yet its identification of prediabetes specific for type 1 diabetes has not been assessed. A composite glucose and C-peptide measure, Index60, identifies individuals at high risk for type 1 diabetes.
We compared Index60 and HbA1c thresholds as markers for type 1 diabetes risk.
TrialNet Pathway to Prevention study participants with ≥ 2 autoantibodies (GADA, IAA, IA-2A, or ZnT8A) who had oral glucose tolerance tests and HbA1c measurements underwent 1) predictive time-dependent modeling of type 1 diabetes risk (n = 2776); and 2) baseline comparisons between high-risk mutually exclusive groups: Index60 ≥ 2.04 (n = 268) vs HbA1c ≥ 5.7% (n = 268). The Index60 ≥ 2.04 threshold was commensurate in ordinal ranking with the standard prediabetes threshold of HbA1c ≥ 5.7%.
In mutually exclusive groups, individuals exceeding Index60 ≥ 2.04 had a higher cumulative incidence of type 1 diabetes than those exceeding HbA1c ≥ 5.7% (P < 0.0001). Appreciably more individuals with Index60 ≥ 2.04 were at stage 2, and among those at stage 2, the cumulative incidence was higher for those with Index60 ≥ 2.04 (P = 0.02). Those with Index60 ≥ 2.04 were younger, with lower BMI, greater autoantibody number, and lower C-peptide than those with HbA1c ≥ 5.7% (P < 0.0001 for all comparisons).
Individuals with Index60 ≥ 2.04 are at greater risk for type 1 diabetes with features more characteristic of the disorder than those with HbA1c ≥ 5.7%. Index60 ≥ 2.04 is superior to the standard HbA1c ≥ 5.7% threshold for identifying prediabetes in autoantibody-positive individuals. These findings appear to justify using Index60 ≥ 2.04 as a prediabetes criterion in this population.
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