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Glucose is an obligate metabolic fuel for the brain. Hypoglycemia should be considered in any pt with confusion, altered level of consciousness, or seizures. Counterregulatory responses to hypoglycemia include insulin suppression and the release of catecholamines, glucagon, growth hormone, and cortisol.

The laboratory diagnosis of hypoglycemia is usually defined as a plasma glucose level <2.5–2.8 mmol/L (<45–50 mg/dL), although the absolute glucose level at which symptoms occur varies among individuals. For this reason, Whipple’s triad should be present: (1) symptoms consistent with hypoglycemia, (2) a low plasma glucose concentration measured by a method capable of accurately measuring low glucose levels (not a glucose monitor), and (3) relief of symptoms after the plasma glucose level is raised.


Hypoglycemia occurs most commonly as a result of treating pts with diabetes mellitus (Table 26-1). Additional factors to be considered in any pt with hypoglycemia are as follows:

  1. Drugs: insulin, insulin secretagogues (especially chlorpropamide, repaglinide, nateglinide), alcohol, high doses of salicylates, sulfonamides, pentamidine, quinine, quinolones

  2. Critical illness: hepatic, renal, or cardiac failure; sepsis; prolonged starvation

  3. Hormone deficiencies: adrenal insufficiency, hypopituitarism (particularly in young children)

  4. Insulinoma (pancreatic β cell tumor), β cell hyperplasia (nesidioblastosis; congenital or after gastric or bariatric surgery)

  5. Other rare etiologies: non–β cell tumors (large mesenchymal or epithelial tumors producing an incompletely processed IGF-II, other nonpancreatic tumors), antibodies to insulin or the insulin receptor, inherited enzymatic defects such as hereditary fructose intolerance and galactosemia.

TABLE 26-1Causes of Hypoglycemia in Adults


Symptoms of hypoglycemia can be divided into autonomic (adrenergic: palpitations, tremor, and anxiety; cholinergic: sweating, hunger, and paresthesia) and neuroglycopenic (behavioral changes, confusion, fatigue, seizure, loss of consciousness, and, if hypoglycemia is severe and prolonged, death). Signs of autonomic discharge, such as tachycardia, cardiac arrhythmia, elevated systolic blood pressure, pallor, and diaphoresis, are typically present in a pt with hypoglycemia awareness but may be absent in a pt with pure neuroglycopenia.

Recurrent hypoglycemia shifts thresholds for the autonomic symptoms and counterregulatory responses to lower glucose levels, leading to hypoglycemic unawareness. Under these circumstances, the ...

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