Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes

Abstract

Type 2 diabetes carries a risk for hypoglycemia, particularly in patients on an intensive glucose control plan as a glucose-lowering strategy, where hypoglycemia may be a limitation for the therapy and also a factor underlying clinical inertia. Glucose-lowering medications that increase circulating insulin in a glucose-independent manner, such as insulin and sulfonylurea therapy, are the most common cause of hypoglycemia. However, other factors such as a delayed or missed meal, physical exercise, or drug or alcohol consumption may also contribute. Specific risk factors for development of hypoglycemia are old age, long duration of diabetes, some concomitant medication, renal dysfunction, hypoglycemia unawareness, and cognitive dysfunction. Hypoglycemia is associated with acute short-term symptoms related to either counterregulation, such as tachycardia and sweating, or to neuroglycopenia, such as irritability, confusion, and in severe cases stupor, coma, and even death. However, there are also long-term consequences of hypoglycemia such as reduced working capacity, weight gain, loss of self-confidence with reduced quality of life, and increased risk for cardiovascular diseases. For both the patients, the health care system, and the society at large, hypoglycemia carries a high cost. Strategies to mitigate the risk of hypoglycemia include awareness of the condition; education of patients, relatives, and health care providers; and selecting appropriate glucose-lowering medication that also judges the risk for hypoglycemia to prevent this complication. This article summarizes the current knowledge of hypoglycemia and its consequences with a special emphasis on its consequences for the choice of glucose-lowering therapy.

Keywords: hypoglycemia; incretin therapy; insulin; sulfonylurea; treatment; type 2 diabetes.

Figure 1

Symptoms and defence mechanisms in relation to glucose levels in the subnormal range.

Figure 2

Mechanisms of glucose counterregulation. Note: Glicagon is secreted from the islet alpha cells in response to hypoglycemia to stimulate glucose production from the liver which raises circulating glucose. Glucagon secretion is stimulated during hypoglycemia by reduced insulin secretion from beta cells, direct action of low glucose on alpha cells, activation of the autonomic nerves and by adrenaline released from the adrenals.