HbA1c trajectories and risk of albuminuria in children and adolescents with type 1 diabetes followed into adulthood - a joint modeling approach of Danish nationwide register data

We examined the association between HbA1c (current value and cumulative exposure) and albuminuria in individuals with childhood-onset type 1 diabetes (T1D). Individuals diagnosed with T1D (0–19 years) were followed in nationwide Danish registers during 1996–2019. Albuminuria was defined as a minimum of two measurements of overnight urine sample > 20 μg/min or urine albumin-creatinine ratio > 30 mg/g within a year. Joint modeling was used to simultaneously analyze HbA1c trajectories and albuminuria as a time-to-event outcome. We compared models including current HbA1c value and area under the HbA1c trajectory (representing cumulative exposure over time) as explanatory variables separately and together. Of 5936 individuals, 795 (13.4%) developed albuminuria during a median (Q1-Q3) follow-up of 10.2 years (6.4–15.8). Current HbA1c value was associated with albuminuria (HR: 1.47 95% CI: 1.37; 1.57 for males and 1.32 95% CI: 1.24; 1.40 for females per 1% (DCCT unit) or 11 mmol/mol (IFCC unit) higher HbA1c). Moreover, a one-unit higher HbA1c area, corresponding to an average 1% higher HbA1c over one year (at any point of follow-up), was associated with 1.05 times the hazard (1.04; 1.06) for males. This is equivalent to a HR of 1.58 (1.45; 1.73) for the same level of exposure sustained over 10 years. Associations between cumulative exposure and albuminuria remained of similar magnitude, when both HbA1c current value and area were included in the model. Cumulative HbA1c exposure was associated with albuminuria independently of current HbA1c, demonstrating the role of long-term glycemic control. Early intervention during childhood and adolescence may have lasting benefits. • Joint modeling linked HbA1c trajectories with long-term albuminuria risk. • Cumulative HbA1c exposure was independently associated with albuminuria risk. • Similar current HbA1c can mask different albuminuria risks due to past exposure. • Interactive tool visualizes hypothetical HbA1c trajectories for clinical interpretation. • Findings support early, sustained HbA1c control to reduce kidney complication risk.