Frequency and Timing of Severe Hypoglycemia Affects Spatial Memory in Children With Type 1 Diabetes

Abstract

OBJECTIVE -Repeated severe hypoglycemia has been reported to reduce long-term spatial memory in children with type 1 diabetes. Early exposure to hypoglycemia may be more damaging to cognitive function than later exposure. Our goal was to determine whether the age at which severe hypoglycemia occurs modulates the impact of severe hypoglycemia frequency on long-term spatial memory.RESEARCH DESIGN AND METHODS -We combined data from three independent studies to obtain a sample of children aged 6 -18 years with type 1 diabetes (n ϭ 103) and nondiabetic control subjects (n ϭ 60). Each study evaluated previous severe hypoglycemia and tested short (5 s)-and long (60 s)-delay spatial memory with the spatial delayed response task. Type 1 diabetic participants were categorized as having zero, one to two, or three or more severe hypoglycemic episodes and as having their first severe hypoglycemic episode before or after 5 years of age. Information on chronic hyperglycemia (HbA 1c values) was also collected.RESULTS -We found that repeated severe hypoglycemia (more than three episodes) reduced long-delay spatial delayed response performance, particularly when severe hypoglycemic episodes began before the age of 5 years. Age of type 1 diabetes onset and estimates of chronic hyperglycemia did not influence performance.CONCLUSIONS -High frequency of and early exposure to severe hypoglycemia during development negatively affects spatial long-term memory performance. Diabetes Care 28:2372-2377, 2005S evere hypoglycemia is a significant and relatively common complication of insulin treatment in children with type 1 diabetes (1). The long-term cognitive effects of such episodes have been debated. One hypothesis is that severe hypoglycemia occurring early in development is more harmful to cognitive function than severe hypoglycemia later in development, but few data address this issue directly. If this hypothesis was correct, it could explain the consistent finding that early onset of type 1 diabetes predicts poorer cognitive function (2-5). Since only individuals with early onset of diabetes would be expected to experience early severe hypoglycemia, age of onset can be confounded with the age of first severe hypoglycemia. Although previous studies (6,7) have examined the impact of age of onset and of severe hypoglycemia history on cognitive function in children, none have established whether the age at which severe hypoglycemia occurs is important in determining cognitive outcome. It is possible that severe hypoglycemia frequency and timing are both important contributors to cognitive dysfunction in children with type 1 diabetes.We combined data from three studies, all of which found that severe hypoglycemia preferentially decreased spatial long-term memory in children with type 1 diabetes (8,9). We used these data to determine how the effects of severe hypoglycemia on spatial memory were modulated by the age at which severe hypoglycemia occurred. Further, we wanted to determine whether exposure to chronic hyperglycemia contributed t...

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