Title:The Science of Hypoglycemia in Patients with Diabetes
Volume: 9
Issue: 3
Author(s): David S. Oyer
Affiliation:
Keywords:
Defective glucose counterregulation, glucose, hypoglycemia, hypoglycemia-associated autonomic failure, type 1
diabetes mellitus, type 2 diabetes mellitus
Abstract: The risk of hypoglycemia with anti-hyperglycemic agents is an important limiting factor in the management of
type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. While hypoglycemia is more common in T1DM, the incidence is
high in T2DM patients who use insulin or secretagogues, particularly patients with longer duration of diabetes. The underlying
cause of hypoglycemia in diabetes is a complex interaction between hyperinsulinemia and compromised physiologic
and behavioral responses to falling glucose levels. Pancreatic dysfunction also causes loss of normal therapeutic response
to hypoglycemia—a reduction in circulating insulin (in T2DM only) and an increase in glucagon secretion. In T1DM and
advanced T2DM, the third defense against hypoglycemia is increase in adrenomedullary sympathoadrenal epinephrine secretion,
which is also compromised, causing the syndrome of defective glucose counterregulation. Diminished increase in
epinephrine, also called hypoglycemia-associated autonomic failure (HAAF), is largely responsible for defective glucose
counterregulation. HAAF can result in recurrent hypoglycemia and lowering of glycemic threshold that typically triggers
sympathoadrenal response to hypoglycemia. This results in hypoglycemia without warning symptoms, or “hypoglycemia
unawareness,” which increases the risk of severe hypoglycemia associated with substantial morbidity and mortality.
Long-term effects of severe hypoglycemia, aside from causing accidents, may include adverse cardiovascular outcomes
and cognitive impairment. To reduce the impact of hypoglycemia, it is important to identify patients at risk and use careful
consideration when choosing antidiabetes medications. Newer insulin analogs that more accurately replicate endogenous
insulin secretion and incretin therapies that cause glucose-sensitive insulin secretion may ultimately reduce the risk
of hypoglycemia.