Standard HbA1c thresholds used to define dysglycemia in autoantibody-positive individuals may overestimate progression risk in adults undergoing surveillance for type 1 diabetes mellitus (T1DM). Findings from a cohort analysis published in Diabetes Care showed that age-adjusted HbA1c values or a higher HbA1c threshold of ≥6.0% produced progression-risk estimates in adults that were more comparable to those observed in children.

The analysis included 5,024 autoantibody-positive relatives enrolled in the TrialNet Pathway to Prevention study, including 3,720 children and 1,304 adults. Age-related HbA1c effects were modeled separately using data from 6,273 adults in the Exeter 10000 population cohort.

Using the standard dysglycemia threshold of HbA1c ≥5.7% (39 mmol/mol), 1-year progression risk among single autoantibody–positive participants was substantially higher in children than adults at 38% (95% CI, 28-47) versus 13% (95% CI, 7.2-19), respectively (P<.001). Among multiple autoantibody–positive participants, progression risk was 55% (95% CI, 49-60) in children and 38% (95% CI, 27-47) in adults (P<.001).

After age adjustment, progression-risk differences between adult and pediatric participants narrowed. In single autoantibody–positive participants, progression risk was 38% (95% CI, 28-47) in children and 27% (95% CI, 13-39) in adults (P=.32). Differences among multiple autoantibody-positive participants were also attenuated.

An HbA1c threshold of ≥6.0% (42 mmol/mol) produced comparable progression risk between adults and children across autoantibody subgroups. In post hoc analyses, adults younger than 30 years had progression risk similar to children (P=.1).

The findings showed that age-related variation in HbA1c influences dysglycemia classification in adults at risk for T1DM. Age-adjusted HbA1c or a higher HbA1c threshold may improve age-specific risk stratification in prevention settings.