A 40-year-old man with type 1 diabetes mellitus comes to the office due to recurrent hypoglycemia. A month ago, the patient was seen in the emergency department due to unconsciousness associated with a blood glucose level of 34 mg/dL. Since then, he has had several blood glucose readings <50 mg/dL that he corrected by drinking fruit juice; however, he had no tremor, sweating, or palpitations during the episodes. Medications include insulin glargine, insulin lispro, lisinopril, hydrochlorothiazide, and simvastatin. Vital signs and physical examination are normal. Hemoglobin A1c is 8.1% and serum creatinine is 1.1 mg/dL. Which of the following is the most likely cause of hypoglycemia unawareness in this patient?
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Patients with type 1 diabetes mellitus can develop hypoglycemia because exogenous insulin continues to be absorbed from the injection site despite falling glucose levels; those with long-standing diabetes (ie, >5 yr) often also have alpha cell failure, which can lead to decreased glucagon secretion and exacerbate hypoglycemia. Normally, hypoglycemia prompts a catecholamine (eg, epinephrine) surge, which increases hepatic glucose production and triggers many of the characteristic neurogenic hypoglycemic symptoms (eg, arousal, tremor). However, patients with long-standing diabetes often have a blunted autonomic response to hypoglycemia, with reduced hypoglycemia awareness.
This blunted autonomic response is worse in patients who frequently have low circulating glucose levels. Such recurrent or severe hypoglycemia reduces the glucose-raising effects of epinephrine and suppresses the symptoms related to the catecholamine surge; in turn, this increases the risk for progressively worse hypoglycemic episodes (ie, hypoglycemia-associated autonomic failure).
Management requires strict avoidance of hypoglycemia to restore awareness. Judicious timing of insulin administration and carbohydrate ingestion (eg, in relation to physical activity) is necessary.
(Choices A, B, and D) Thiazide diuretics (eg, hydrochlorothiazide) and statins (eg, simvastatin) can raise blood glucose levels, making glycemic control somewhat more difficult. In contrast, ACE inhibitors (eg, lisinopril) increase insulin sensitivity and can occasionally induce hypoglycemia. However, these agents do not significantly affect hypoglycemia awareness.
Educational objective:
Hypoglycemia normally prompts a catecholamine (eg, epinephrine) surge, which increases hepatic glucose production and triggers hypoglycemic symptoms. Recurrent or severe hypoglycemia in patients with long-standing diabetes reduces the glucose-raising effects of epinephrine and suppresses the symptoms related to the catecholamine surge, increasing the risk for progressively worsening hypoglycemic episodes.