Glycemic Extremes Impact Brain Function in Teens With Type 1 Diabetes

Activity in certain brain regions of teenagers with type 1 diabetes was increased or decreased with hyperglycemia and hypoglycemia.

BOSTON — In adolescents with type 1 diabetes, hyperglycemia and hypoglycemia were associated with changes in neuronal activity in certain brain regions, with abnormalities persisting even after recovery to euglycemia, according to a new study presented at the American Diabetes Association (ADA) 75th Scientific Sessions.

The adverse effects of hyperglycemia and hypoglycemia on cognition, including subtle effects on overall IQ, attention information processing and higher order executive functions, as well as reductions in the brain’s grey and white matter in the brain, have been well documented in various studies.

“Despite these advances, however, the specific neurobiological mechanisms that may underlie these changes are not well understood,” Michele A. O’Connell, MD, FRACP, of The Royal Children’s Hospital and Murdoch Children’s Research Institute in Melbourne, Australia, said during a presentation.

In particular, O’Connell noted that the longitudinal studies documenting these effects show that these changes are acquired over time, and the effects are cumulative, making it difficult to disentangle the potential causative neural insults. Further, although studies have illustrated significant differences in brain function during abnormal glycemia in adults, limited data exist in the pediatric population.

Using functional MRI (fMRI), which allows for noninvasive assessments of brain function, O’Connell and colleagues were able to examine in greater detail what occurs in the brains of young patients with type 1 diabetes during glycemic extremes.

They conducted a prospective study of 20 adolescents with type 1 diabetes (median age, 16.4 years). Median duration of diabetes was 7.7 years, and median HbA1c was 6.9%. Standard insulin clamp techniques were used to manipulate glycemia. Ten patients were studied during hypoglycemia and 10 during hyperglycemia, and recovery to euglycemia was evaluated in all patients.

The researchers performed fMRI at rest and during a working memory task in each state. As part of this study, they also assessed neuronal activity and perfusion using blood oxygen level dependent (BOLD) signaling and arterial spin labeling (ASL).

Results revealed that hypoglycemia was associated with significantly decreased neuronal activity (BOLD) in the temporoparietal cortex, which is a major working memory hub. However, hyperglycemia was linked to both significantly increased BOLD signaling in the basal ganglia and left frontal cortex.

Hyperglycemia was also associated with significantly increased brain perfusion (ASL), according to the data. This was most pronounced in the basal ganglia and subcortical regions.

Additionally, the investigators noted that in each instance, neuronal activity at recovery differed from baseline.

“Cerebral blood flow and brain activity were significantly increased in areas known to be involved in working memory … The multiple areas of significant change seen indicate that during glycemic extremes, the brain needs to adapt and appears to preference certain regions over others,” O’Connell said.

“In conclusion, acute hypoglycemia and hyperglycemia have profound impacts on brain function in adolescents with type 1 diabetes. The combination of ASL and fMRI provides a novel multimodal approach to extend this work and examine further important questions relating to the effects of diabetes on the brain.”


  1. O’Connell MA et al. Abstract 379-OR: Mechanisms of Acute Dysglycemic Brain Function in T1D. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.