Resumen de Performance of HbA^sub 1c^ as an Early Diagnostic Indicator of Type 1 Diabetes in Children and Youth

Rendra Vehik, David Cuthbertson, David Boulware, Craig Beam, Henry Rodriguez, Laurent Legault, Mila Hyytinen, Marian J. Rewers, Desmond Schatz, Jeffrey Krischer

• The aim of this study was to evaluate HbA^sub 1c^ as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age. Subjects <21 years of age who participated in the prospective DPT-1, TEDDY, TRIGR, and Type 1 Diabetes TrialNet Natural History (TrialNet) studies and had an HbA^sub 1c^ within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140-199 mg/dL defined IGT, and an OGTT with 2-hPG ?200 mg/dL or fasting plasma glucose ?126 mg/dL defined diabetes. HbA^sub 1c^ ?5.7% defined IGT, and HbA^sub 1c^ ? 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA^sub 1c^ compared with OGTT. There were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA^sub 1c^ sensitivity was very low across the studies (8-42%), and specificity was variable (64-95%). With HbA^sub 1c^ ?6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA^sub 1c^ ?6.5% for the development of T1D was variable (50-94%) across the four studies. HbA^sub 1c^ ?6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA^sub 1c^ threshold is recommended if used as an alternative criterion in diagnosing T1D.