Keywords:

One common effect of recurrent hypoglycemia is diminished release of stress hormones during hypoglycemia: increased amygdala responsiveness caused by recurrent hypoglycemia could, perhaps, be a beneficial adaptation that would oppose and attenuate reduced awareness of hypoglycemia. Stress hormones including epinephrine and glucocorticoids are key modulators of cognitive function, and especially of improved performance at times of moderate stress, effects that are transduced via the amygdala; it is hence possible that an increase in amygdala responsiveness may be adaptive in acting to positively modulate other brain regions [in particular, the hippocampus] even when systemic hormone release is attenuated. Importantly, though, one study that examined amygdala metabolism in humans, during hypoglycemia, found that in contrast to the present findings fluorodeoxyglucose uptake was better maintained in the amygdala of aware vs unaware patients; this is in contrast to our data that suggest increased amygdala activity in the recurrent hypoglycemia animals which would be expected to correspond to hypoglycemia-unaware patients. Although there are significant methodological differences as well as a species difference between the studies, this finding does constrain the ability to generalize from the small dataset presented here. It is also true that stress-related hormones, particularly epinephrine, are released when hypoglycemic but such release diminishes after recurrent hypoglycemia: thus, the enhanced anxiety in the recurrent hypoglycemia-hypo group observed here is somewhat paradoxical and the amygdala’s response to stress hormones under such conditions may repay further study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653740/