Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned. (JINS, 2016, 21, 293–302)

The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4–10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. (JINS, 2014, 20, 238–247)

Performance on long delays of delayed response tasks is associated with medial temporal function, a region of the brain affected by severe hypoglycemia. A previous study showed that children with type 1 diabetes mellitus (T1DM) with higher risk for severe hypoglycemia performed worse than controls on long delays of a spatial delayed response (SDR) task. We tested the more specific hypothesis that frequency of severe hypoglycemia would relate to long delay SDR performance. Children with T1DM (n = 51) and controls (n = 32) performed the SDR task with short and long delays. Information was collected on children's past severe hypoglycemia. In children with T1DM, number of past severe hypoglycemic episodes accounted for a significant portion of the variance in long delay SDR after controlling for age and age of onset. This relationship was not seen with short delay SDR or with other tasks (verbal or object memory, attention, motor speed). These results support the hypothesis that severe hypoglycemia has specific, negative effects on memory skills in children. If this relationship is extrapolated to children with higher frequency of severe hypoglycemia, due to longer duration of disease or poorer glucose control, it may affect daily functioning and thus need to be considered in treatment decisions. (JINS, 2003, 9, 740–750.)

Previous studies of the neuropsychological consequences of insulin dependent diabetes mellitus (IDDM) have had mixed and often contradictory results, possibly due to the heterogeneity of the samples and neuropsychological measures, and a lack of specific hypotheses. In order to address this problem, we focused on the effect of severe hypoglycemia on memory functioning in a relatively homogeneous sample of childhood-onset IDDM patients. Given the deleterious effects of hypoglycemia on medial temporal lobe structures (e.g., hippocampus) and the relationship between medial temporal damage and declarative memory functioning, we hypothesized that those patients who had experienced severe hypoglycemia would demonstrate impaired declarative memory and spared nondeclarative memory functioning. Results of the study were generally consistent with this hypothesis, although some impact of hypoglycemia was observed on perceptual priming ability. (JINS, 1997, 3, 509–520.)