Hypoglycemia

Hypoglycemia rarely exists in humans outside diabetes mellitus treated with insulin and/or sulfonylureas. Because hypoglycemia produces marked discomfort, lasting for hours, and may progress to severe neuroglycopenia with cognitive dysfunction, unconsciousness, sometimes even epilepsy, hypoglycemia is highly feared by patients. Hypoglycemia may increase the cardiovascular risk of affected and/or elderly patients and is long-term associated with risk of dementia. In type 1 diabetes and also in those type 2 patients who lose β-cell function nearly totally, there is impaired response of glucagon to hypoglycemia which predisposes to a higher risk for hypoglycemia. In turn, recurrent hypoglycemia results in brain adaptation with loss of other counterregulatory hormones, primarily adrenaline, and symptom responses (hypoglycemia unawareness). This creates a vicious circle which predisposes to severe hypoglycemia. However, prevention of hypoglycemia in patients with hypoglycemia unawareness may recover both hormonal and symptoms responses to hypoglycemia thus reducing the risk for severe hypoglycemia. Prevention of hypoglycemia is therefore a key issue in insulin treatment. Education of patients, use of modern SMPG and CGM systems, harmonization of rapid-acting and long-acting analogues of insulin (in place of human insulin) reduce the risk for hypoglycemia. To reduce the risk for hypoglycemia in type 2 diabetes, basal should be preferred to prandial insulin. If postprandial hyperglycemia requires treatment, GLP-1RAs should be added in place of prandial insulin whenever possible. In addition, sulfonylureas should not be initiated and withdrawn if in use, and DPP-IV started instead. The optimal treatment of diabetes is the combination of an A1C level individualized for the personal characteristics of the patient and minimal risk for hypoglycemia.