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.

AIMS: We examined the association between HbA1c (current value and cumulative exposure) and albuminuria in individuals with childhood-onset type 1 diabetes (T1D).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.