Brain Regulation of Cardiac Function during Hypoglycemia

Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this fall in glucose. The autonomic nervous system innervates the heart, and during hypoglycemia, can cause many changes. Clinical and animal studies have revealed changes in electrocardiograms during hypoglycemia. Cardiac repolarization defects (QTc prolongation) occur during moderate levels of hypoglycemia. When hypoglycemia is severe, it can be fatal. Cardiac arrhythmias are thought to be the major mediator of sudden death due to severe hypoglycemia. Both the sympathetic and parasympathetic nervous systems of the brain have been implicated in regulating these arrhythmias. Besides cardiac arrhythmias, hypoglycemia can have profound changes in the heart and most of these changes are exacerbated in the setting of diabetes. A better understanding of how the brain regulates cardiac changes during hypoglycemia will allow for better therapeutic intervention to prevent cardiovascular death associated with hypoglycemia in people with diabetes. The aim of this paper is to provide a narrative review of what is known in the field regarding how the brain regulates the heart during hypoglycemia.