Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus

Objective: Despite the general consensus that youth with type 1 diabetes mellitus (T1DM) can experience modest cognitive impairment, debate continues over the role of severe hypoglycemia (Hypo) and/or hyperglycemia (Hyper) in producing such impairment. Our aim was to determine how Hypo and Hyper experienced during brain development predict patterns of subsequent cognitive performance in youth with T1DM. Methods: We tested youth aged 5-16 yr (T1DM, n = 117; non-diabetic sibling controls, n = 58) on cognitive tasks (verbal and spatial intelligence, verbal and spatial memory, and processing speed). T1DM participants were categorized as having experienced 0, 1-2, or 3 or more (3+) Hypo episodes, as having their first Hypo episode before or after 5 yr of age and as having early (before age 5) or late (after age 5) diabetes onset. Hyper exposure was estimated with median hemoglobin A1c, adjusted for diabetes duration for each subject. Results: The group with T1DM had lower estimated verbal intelligence than sibling controls. Within the T1DM group, verbal intelligence was reduced with increased exposure to Hyper, not to Hypo. In contrast, spatial intelligence and delayed recall were reduced only with repeated Hypo, particularly when Hypo episodes occurred before the age of 5 yr. Age of onset did not explain these results. Conclusions: Hypo and Hyper have qualitatively different effects on cognitive function in T1DM that depend in part on the timing of exposure during development, independent of onset age. This information extends the known benefits of avoiding both Hypo and chronic Hyper during childhood to include preservation of specific cognitive skills.