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Hypoglycemia is most commonly caused by drugs used to treat diabetes mellitus or by exposure to other drugs, including alcohol. However, a number of other disorders, including critical organ failure, sepsis and inanition, hormone deficiencies, non-β-cell tumors, insulinoma, and prior gastric surgery, can cause hypoglycemia (Table 26-1). Hypoglycemia is most convincingly documented by Whipple’s triad: (1) symptoms consistent with hypoglycemia, (2) a low plasma glucose concentration measured with a precise method (not a glucose monitor), and (3) relief of symptoms after the plasma glucose level is raised. The lower limit of the fasting plasma glucose concentration is normally ∼70 mg/dL (∼3.9 mmol/L), but lower venous glucose levels occur normally, late after a meal, during pregnancy, and during prolonged fasting (>24 h). Hypoglycemia can cause serious morbidity; if severe and prolonged, it can be fatal. It should be considered in any patient with episodes of confusion, an altered level of consciousness, or a seizure.
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SYSTEMIC GLUCOSE BALANCE AND GLUCOSE COUNTERREGULATION
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Glucose is an obligate metabolic fuel for the brain under physiologic conditions. The brain cannot synthesize glucose or store more than a few minutes’ supply as glycogen and therefore requires a continuous supply of glucose from the arterial circulation. As the arterial plasma glucose concentration falls below the physiologic range, blood-to-brain glucose transport becomes insufficient to support brain energy metabolism and function. However, redundant glucose counterregulatory mechanisms normally prevent or rapidly correct hypoglycemia.
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Plasma glucose concentrations are normally maintained within a relatively narrow range—roughly 70–110 mg/dL (3.9–6.1 mmol/L) in the fasting state, with transient higher excursions after a meal—despite wide variations in exogenous glucose delivery from meals and in endogenous glucose utilization by, for example, exercising muscle. Between meals and during fasting, plasma glucose levels are maintained by endogenous glucose production, hepatic glycogenolysis, and hepatic (and renal) gluconeogenesis (Fig. 26-1). Although hepatic glycogen stores are usually sufficient to maintain plasma glucose levels for ∼8 h, this period can be shorter if glucose demand is increased by exercise or if glycogen stores are depleted by illness or starvation.
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