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

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 Ͼ7.5 g/min and Ͼ20 g/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 HbA 1c 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. Diabetes Care 26:1224 -1229, 2003P arents and health professionals caring for very young children with diabetes must balance the opposing risks of hypoglycemia and future microvascular complications. Although the importance of avoiding severe hypoglycemia in children age Ͻ5 years is well documented (1-3), the relative contribution of these prepubertal years to the development of complications remains less certain (4).In an earlier study using logistic regression, researchers demonstrated that longer prepubertal diabetes duration increased the risk of retinopathy, but not microalbuminuria, in adolescents (5). Studies using survival analysis have also demonstrated that the duration during prepubertal years contributes to retinopathy (6 -8), and one study has demonstrated the contribution of prepubertal duration to microalbuminuria (9). Total duration as a continuous variable was not a significant predictor of microalbuminuria in a Norwegian study, but onset of diabetes before age 13 years conferred an increased risk compared to onset after age 13 years (10). In contrast, a recent study assessing urinary albumin concentration in chil...

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