Current ADA standards include HbA1c values 5.7%-6.4% as an indicator of prediabetes. However, there is little information with regard to HbA1c as a specific predictor of T1D. We thus compared HbA1c with Index 60, a T1D marker, for identifying individuals at high risk for T1D. Index 60 was derived from a proportional hazards regression model for T1D that included log fasting C-peptide, 60-minute glucose, and 60-minute C-peptide. Diabetes Prevention Trial-type 1 participants with Index 60<2.00 at baseline were followed for the first (incident) OGTT exceeding an Index 60≥2.00 threshold (n=85). Similarly, those with HbA1c values <6.0% at baseline were followed for the first (incident) HbA1c ≥6.0% (n=77). Those with both incident Index 60≥2.00 and incident HbA1c ≥6.0 were excluded. At the incident OGTTs, those with HbA1c ≥6.0 were older (19.2±12.2 years vs. 12.7±7.2 years; p<0.001). The cumulative incidence for T1D was higher (log rank p<0.001) after Index 60≥2.00 than after HbA1c ≥6.0 (3- and 4-year risks for HbA1c ≥6.0: 0.41 and 0.45; 28/77 diagnosed vs. 3- and 4-year risks for Index 60≥2.00: 0.78 and 0.92; 60/85 diagnosed). The hazard ratio for Index 60≥2.00 vs. HbA1c ≥6.0 (with age adjustment) was significant [HR: 1.96 (1.20, 3.16); p=0.006]. Intervals from incident Index 60≥2.00 and HbA1c ≥6.0 to diagnosis were 1.2±0.9 (0.1-3.8) years and 1.0±1.0 (0-4.7) years, respectively (p=0.50). The 59 individuals who had OGTTs on the date of incident HbA1c ≥6.0 had higher 30-0 minute C-peptide (with age adjustment) than those with incident Index 60≥2.00 (2.8±1.9 ng/ml vs. 1.6±1.0 ng/ml; p<0.001).

In conclusion, Index 60≥2.00 was superior to HbA1c ≥6.0 at identifying individuals at high risk for T1D. Moreover, those with incident HbA1c ≥6.0 were much older with higher C-peptide levels, suggesting heterogeneity. These findings add support for including C-peptide together with glucose in developing predictors and pre-diagnostic endpoints that are specific for T1D.


L.M. Jacobsen: None. H.M. Ismail: None. M.A. Clements: Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Glooko, Inc.. D. Schatz: None. J. Sosenko: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at