Hypoglycemia as a cause of cardiovascular injury

While insulin resistance and pre-diabetic but elevated glucose levels are widely recognized as  contributors to cardiovascular disease, it is less well-known that hypoglycemia also damages the cardiovascular system. A study just published in the journal Diabetic Medicine reports on one of the mechanisms:

"Intensive glycaemic control increases the incidence of hypoglycaemia. We sought to define the effects of hypoglycaemia on aldosterone, a hormone involved in cardiovascular injury and baroreflex impairment."

The authors examined the effects of hypoglycaemia and normal blood sugar (euglycemia) on aldosterone and plasma renin activity through the use of the hypoglycaemic hyperinsulinaemic clamp protocol in which the glucose is dropped in a controlled fashion with insulin. What did the data show?

"In Study 1, aldosterone increased approximately 2.5-fold during hypoglycaemic hyperinsulinaemia but did not rise with euglycaemic hyperinsulinaemia. In Study 2, aldosterone increased significantly at glucose levels of 2.8 mmol/l; this increase was amplified with glucose of 2.2 mmol/l. Aldosterone increases paralleled those of ACTH."

Parallel increases of ACTH (adrenacorticotropic hormone) show that the aldosterone increase is part of the hypothalamus-pituitary-adrenal  axis reaction to hypoglycemia. Regarding the signficance for cardiovascular disease, the authors state in conclusion:"Hypoglycaemia increases aldosterone in a dose-dependent fashion...Because aldosterone activation of the mineralocorticoid receptor is implicated in the pathophysiology of cardiovascular injury, including vascular dysfunction, inflammation, baroreflex impairment and cardiac arrhythmias, these findings may be of relevance in individuals who experience hypoglycaemia."