Exercise-Related Hypoglycemia-Associated Autonomic Failure in Diabetes

Iatrogenic hypoglycemia is the limiting factor in the glycemic management of diabetes (1,2). It causes recurrent morbidity in most people with type 1 diabetes as well as many with advanced type 2 diabetes and is sometimes fatal. It precludes maintenance of euglycemia over a lifetime of diabetes and, therefore, full realization of the benefits of glycemic control. It compromises physiological and behavioral defenses against subsequent falling plasma glucose concentrations and thus causes a vicious cycle of recurrent hypoglycemia. Insight into the pathophysiology of glucose counterregulation will continue to lead to understanding of the frequency and impact of, risk factors for, and prevention of iatrogenic hypoglycemia (1,2).

Marked absolute therapeutic hyperinsulinemia can cause isolated episodes of hypoglycemia in people with diabetes. However, episodes of hypoglycemia are more typically the result of the interplay of relative or mild-moderate absolute therapeutic hyperinsulinemia and compromised physiological and behavioral defenses against falling plasma glucose concentrations (1,2) (Fig. 1). The compromised physiological defenses include loss of decrements in β-cell insulin, loss of increments in α-cell glucagon, and, given the latter, attenuation of increments in adrenomedullary epinephrine. The compromised behavioral defense is the failure of carbohydrate ingestion resulting from loss of symptoms, which is largely the result of an attenuated sympathetic neural response. The concept of …