Do All Prepubertal Years of Diabetes Duration Contribute Equally to Diabetes Complications?

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Abstract
OBJECTIVE—This study was designed to explore the timeline of protection against complications in prepubertal children with diabetes, in particular the effects of diabetes duration before age 5 years. RESEARCH DESIGN AND METHODS—In this study, 193 adolescents with prepubertal diabetes onset were followed longitudinally for retinopathy (early background and clinical) and microalbuminuria (albumin excretion rate >7.5 μg/min and >20 μg/min). Multiple logistic regression analysis was used to compare the effect of pre- and postpubertal diabetes duration on the risk of each complication in 90 subjects reassessed as young adults. For the entire cohort, Kaplan-Meier estimates were used to determine time free of each complication, and survival was compared in those diagnosed before and after age 5 years. Accelerated failure time modeling was used to estimate the effect of covariates, including diabetes duration before puberty, on the risk of complications. RESULTS—Prepubertal duration improved the prediction for retinopathy over postpubertal duration alone in the young adults. The survival-free period of retinopathy and microalbuminuria was significantly longer (2–4 years) for those diagnosed before age 5 years compared with those diagnosed after age 5 years. Time to onset of all complications increased progressively with longer diabetes duration before gonadarche. Higher HbA1c during adolescence had an independent effect on the risk of retinopathy and microalbuminuria. CONCLUSIONS—Prepubertal diabetes duration remains a significant predictor of retinopathy in young adults. The effect of time on the risk of retinopathy and microalbuminuria is nonuniform, with an increasing delay in the onset of complications in those with longer prepubertal duration. These findings are of major clinical importance when setting targets of glycemic control in young children who are at greatest risk of hypoglycemia.