Index60 Is Superior to HbA1c for Identifying Individuals at High Risk for Type 1 Diabetes

Context 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. Objective We compared Index60 and HbA1c thresholds as markers for type 1 diabetes risk. Methods 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%. Results 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). Conclusion 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.

Automated summary

Individuals with an Index60 ≥ 2.04 have a greater risk for type 1 diabetes with more characteristic features of the disorder compared to those with an HbA1c ≥ 5.7%. Therefore, using an Index60 ≥ 2.04 as a criterion for prediabetes in autoantibody-positive individuals appears to be justified.