A 62-year-old woman is brought to the emergency department after a fall and is found to have a left femoral neck fracture. The patient is admitted to the hospital, and a hip arthroplasty is planned. Medical history is significant for long-standing type 2 diabetes mellitus, hypertension, hyperlipidemia, and migraines. While hospitalized, the patient receives a combination of long- and short-acting insulin for diabetes management. On the morning of surgery, fasting blood glucose level is 42 mg/dL. The patient is awake and alert and says she feels hungry but has no other symptoms of hypoglycemia. Concurrent use of which of the following medications best explains this finding?
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Prolonged hypoglycemia can lead to irreversible neurologic deficits and death. To prevent injury, counterregulatory systems raise blood glucose in response to hypoglycemia via sympathetic nervous system activation (ie, norepinephrine/epinephrine release) and increase secretion of glucagon, cortisol, and growth hormone.
Symptoms of hypoglycemia fall into 2 general categories: neurogenic (autonomic) and neuroglycopenic.
This patient has reduced awareness of hypoglycemia, likely due to the use of a nonselective beta blocker (eg, propranolol) for chronic treatment of migraines and/or hypertension. Nonselective beta blockers attenuate the norepinephrine/epinephrine-mediated symptoms of hypoglycemia, but cholinergic symptoms (eg, hunger) are unaffected. In addition, nonselective beta blockers can contribute to the severity of hypoglycemia; epinephrine stimulates hepatic gluconeogenesis and peripheral glycogenolysis, but this effect is diminished by nonselective beta blockers.
(Choices A and C) Statins (eg, atorvastatin) and hydrochlorothiazide can increase blood glucose levels but would not mask symptoms of hypoglycemia.
(Choice B) Insulin-secreting pancreatic beta cells have alpha-2 and beta-2 receptors; stimulation of alpha-2 receptors inhibits insulin secretion, whereas stimulation of beta-2 receptors increases insulin secretion. Doxazosin is a selective alpha-1 blocker and has no effect on glucose levels.
(Choices D and F) Angiotensin II receptor blockers (eg, losartan) and nondihydropyridine calcium channel blockers (eg, verapamil) do not mask the symptoms of hypoglycemia and have virtually no effect on glucose levels.
Educational objective:
Nonselective beta blockers exacerbate hypoglycemia and mask hypoglycemic symptoms mediated by norepinephrine/epinephrine.