Clinical presentation and memory function in youth with type 1 diabetes

Abstract

Objective While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer-term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. Methods Cognitive testing was performed on children 7–17 years old with T1DM (n=66) within 3.5 months of diagnosis and siblings without T1DM (n=33). Overall intelligence, processing speed and memory (including a sensitive long-delay spatial memory test; Spatial Delayed Response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. Results Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p=0.006). In addition, within the group with T1DM higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p=0.027). Performance on the other cognitive tasks was not different across groups or subgroups. Conclusions DKA and degree of hyperglycemia exposure at diagnosis have implications for long delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function.

Severity of clinical presentation in youth with type 1 diabetes is associated with differences in brain structure

“…Despite the high prevalence of these complications at diagnosis in childhood, few studies have investigated their longer-lasting impact on the brain. In a previous paper, we found an association between DKA and hyperglycemia at diagnosis and memory performance approximately 3 months post-diagnosis in children with type 1 diabetes (21). Moreover, a recent study found that DKA at diagnosis was associated with differences in white matter diffusivity and volume days afterwards, most of which resolved by 6 months.…”

“…Animal studies have shown that hyperglycemia and DKA can lead to varying degrees of dysfunction in the hippocampus (44–46) and human studies have linked severity of clinical presentation in youth with type 1 diabetes to decreased delayed memory performance, a critical function of the hippocampus (5, 21, 22). Unfortunately, in our dataset, we had few subjects with both valid imaging and cognitive data to perform correlations between these two outcomes with adequate power.…”

Cognition and Type 1 Diabetes in Children and Adolescents

“…These differences in memory function were present even when there was no clinically apparent cerebral edema. We previously found that, after adjusting for age, sex, and socioeconomic status, youth with type 1 diabetes and a DKA event at diagnosis performed worse on a long-delay memory task 4 months after diagnosis compared to sibling control subjects (42). Another study found that youth presenting with DKA at diagnosis had poorer performance on a verbal delayed memory task and a mental state task within 48 hours of diagnosis compared to those presenting without such an event at diagnosis (43).…”

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis

“…1–3 Among patients without obvious neurologic decline during treatment for diabetic ketoacidosis, subtle neurologic alterations are often present after recovery, including deficits in memory, attention, and IQ 4–7 and changes in cerebral microstructure. 4,8,9 …”