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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. Additional factors to be considered in any pt with hypoglycemia are listed below.

  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


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, 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 first manifestation of hypoglycemia is neuroglycopenia, placing pts at risk of being unable to treat themselves.


Diagnosis of the hypoglycemic mechanism is critical for choosing a treatment that prevents recurrent hypoglycemia (Fig. 24-1). Urgent treatment is often necessary in pts with suspected hypoglycemia. Nevertheless, blood should be drawn at the time of symptoms, whenever possible before the administration of glucose, to allow documentation of hypoglycemia as the cause of symptoms. If the glucose level is low and the cause of hypoglycemia is unknown, additional assays should be performed on blood obtained at the time of a low plasma glucose. These should include insulin, proinsulin, C-peptide, sulfonylurea levels, cortisol, and ethanol. In the absence of documented spontaneous hypoglycemia, overnight fasting or food deprivation during observation in the outpatient setting will sometimes ...

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