Functional MRI in adolescents with type 1 diabetes revealed diminished or increased activity in different brain regions during periods of hypoglycemia and hyperglycemia, - and recovery to euglycemia did not return neuronal activity to baseline levels, according to research presented at the American Diabetes Association’s 75th Scientific Sessions.

“Functional MRI techniques allow for noninvasive assessment of brain function, and studies now looking at healthy adults and diabetic adults have shown significant differences in brain function during abnormal glycemia, mostly hypoglycemia to date; however, there are limited data from pediatric cohorts and differences may exist as a function of ongoing neurodevelopment or age,” Michele A. O’Connell, MB, BAO, MRCPI, FRACP, of The Royal Children’s Hospital in Melbourne, Australia, said during a presentation.

In a prospective study, O’Connell and colleagues enrolled 20 patients aged 12 to 18 years with type 1 diabetes to undergo functional MRI while at rest and while performing a working memory task during baseline euglycemia (5 ± 0.5 mmol/L), hypoglycemia (2.6 ± 0.5 mmol/L; n = 10) or hyperglycemia (18-20 ± 0.5 mmol/L; n = 10) using standard insulin clamp techniques.

Researchers used group-level t tests to identify areas of brain activation. Significantly decreased neuronal activity indicated by blood oxygen level dependent (BOLD) signaling was observed in the temporoparietal cortex, which is a major working memory hub, in participants experiencing hypoglycemia. The brains of participants experiencing hyperglycemia exhibited both significantly increased BOLD signal in the basal ganglia and left frontal cortex and significantly increased brain perfusion indicated by arterial spin labeling in the basal ganglia and subcortical regions. Brain activity during the recovery period differed from baseline in the hypoglycemia and hyperglycemia groups.

“This study is one of the first to describe mechanisms of acute brain dysfunction in [type 1 diabetic] youths during glycemic extremes. We have shown differential mechanistic and regional effects of hypo- and hyperglycemia with persistent abnormalities in neuronal activity at recovery despite euglycemia. This experimental paradigm will allow neuroprotective therapeutic options to be explored,” the researchers wrote.

“By design, we chose to place particular emphasis on working memory, and therefore these regions were important to us,” O’Connell said. “The multiple areas of significant change indicate that during glycemic extremes, the brain needs to adapt and appears to preference certain regions over others.” – by Jill Rollet


O’Connell MA, et al. Abstract 379-OR. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.

Disclosure: O’Connell reports research support from Juvenile Diabetes Research Foundation and Pfizer.





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