Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes

Context: There is a paucity of data regarding the association between glycosylated hemoglobin (HbA(1c)) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D). Objective: To investigate the association between HbA(1c) variability and risk of microvascular complications in adolescents with T1D. Design: Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y). Setting: Tertiary pediatric hospital. Participants: A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8). Main Outcome Measures: Glycemic variability was computed as the SD of all HbA(1c) measurements (SD-HbA(1c)) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time-and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA(1c) variability, after adjusting for known risk factors, including HbA(1c), diabetes duration, blood pressure, and lipids. Results: In multivariable analysis, SD-HbA(1c) was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00-1.73), albuminuria (OR 1.81; 1.04-3.14), increased log(10) albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy. Conclusions: Greater HbA(1c) variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications.