30-Year Trends in Microvascular Complications and Treatment in Adolescents With Type 1 Diabetes

To examine trends in microvascular complications in adolescents from 1990 to 2019.

Retinopathy, albuminuria, and peripheral and autonomic nerve function (pupil size and heart rate variability [HRV]) were assessed in 2,761 adolescents aged 12-20 years (duration ≥5 years) over 5,487 visits. Generalized estimating equations were used to examine the association between decades T1 (1990-1999), T2 (2000-2009), and T3 (2010-2019), and modifiable risk factors, including HbA1c variability, were assessed by coefficient of variation (CV).

Retinopathy (T1 40%, T2 21%, T3 20%; P < 0.001) and early elevation of mean albumin-to-creatinine ratio (ACR) (T1 35%, T2 29%, T3 28%; P = 0.009) plateaued and peripheral nerve abnormality rates decreased (T2 35%, T3 28%; P = 0.007), while HRV abnormality (T2 37%, T3 38%; P = 0.884) and albuminuria (T1 6%, T2 4%, T3 4%; P = 0.164) were unchanged. Over time, multiple daily injection (MDI)/continuous subcutaneous insulin infusion (CSII) use increased, with a decrease in the proportion of adolescents achieving HbA1c <7.0% (T1 7.4%, T2 9.6%, T3 14.1%). In a multivariable model including HbA1c, HbA1c CV, diabetes duration, diastolic blood pressure, and insulin dose per kilogram body weight, retinopathy and early elevation of albumin excretion rate (AER) were associated with twice-daily insulin versus MDI/CSII (odds ratio 1.59 [95% CI 1.23-2.06; P < 0.001], 1.26 [1.06-1.48]; P = 0.007]). After adjusting for mean intrapersonal HbA1c, higher HbA1c CV was associated with early elevation of AER/ACR (1.27 [1.05-1.53; P = 0.015]), albuminuria (1.26 [1.04-1.52; P = 0.018]), and HRV abnormality (1.49 [1.08-2.05; P = 0.015]).

Diabetes complications decreased then plateaued over time. These findings support lower glycemic targets, CSII use, and targeting of modifiable risk factors and HbA1c CV to reduce complications risk in youth with type 1 diabetes. The role of hybrid closed-loop therapy should be evaluated in the future.