Elsevier

The Journal of Pediatrics

Volume 153, Issue 3, September 2008, Pages 385-390
The Journal of Pediatrics

Original article
Prevalence of Structural Central Nervous System Abnormalities in Early-Onset Type 1 Diabetes Mellitus

https://doi.org/10.1016/j.jpeds.2008.03.005Get rights and content

Objective

To characterize the effects of severe hypoglycemia on the developing brain in children with early-onset type 1 diabetes mellitus (T1DM).

Study design

Children diagnosed with T1DM before age 6 years were studied. Those with prospectively monitored severe hypoglycemia (coma/seizure; n = 32) were compared with age-matched peers (n = 30) with no history of such events using magnetic resonance imaging. Glycemic control (evaluated based on glycated hemoglobin [HbAlc] level), episodes of diabetic ketoacidosis (DKA), and clinical variables were monitored continuously since diagnosis in all subjects.

Results

Mean HbAlc from diagnosis and the duration of T1DM were similar in those with and without a history of severe hypoglycemia (9.0% ± 0.9% vs 8.8% ± 0.9%; 7.2 ± 2.7 years vs 6.7 ± 2.3 years). A high prevalence of central nervous system (CNS) structural abnormalities was detected (29%), and mesial temporal sclerosis (MTS) was detected in 16% of the total sample (n = 62). The presence of MTS was not associated with a history of severe hypoglycemia or DKA. Analysis of brain matter volumes suggested relatively less gray matter density in those subjects with a history of severe hypoglycemia.

Conclusions

Early age of onset of T1DM per se is associated with a high incidence of CNS abnormalities, particularly MTS, suggesting hippocampal damage. Early-onset severe hypoglycemia may have an effect on gray matter volume.

Section snippets

Methods

Subjects were drawn from the Western Australian Children's diabetes database, which was established in 1987 at Princess Margaret Hospital. Because this hospital is the only pediatric diabetes referral center in Western Australia, where almost all (99.8%) diagnosed children in the state are registered and treated,29 a representative sample of children with T1DM was potentially available for inclusion. Subjects were considered eligible for the study if they had been diagnosed with T1DM by age 6

Results

Subjects in the no seizure group were well matched with subjects from the combined seizure group on all clinical characteristics, including sex (Table I). The early first seizure subgroup was younger than the rest of the seizure group at diagnosis (2.1 ± 0.9 years vs 3.8 ± 1.4 years; P < .05) and also at the time of the first severe hypoglycemic episode (4.2 ± 1.2 years vs 7.3 ± 1.6 years; P < .05). This was expected, because the division of the experimental group was based on age at the first

Discussion

In this study, we aimed to determine whether documented severe hypoglycemia in subjects with early-onset T1DM is associated with structural abnormalities in the brain as detected by MRI. By using a comparison group of early-onset TIDM children with no history of severe hypoglycemia, we sought to control for other effects related to T1DM per se.

The main findings from this study are the high prevalence of MTS in the total study cohort and the comparable MRI results in those with and those without

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    Supported by a Juvenile Diabetes Foundation International grant (1-1999-597).

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