Abstract

Plasma glucose concentration is usually maintained in a narrow range due to a balance between glucose influx and glucose efflux. Hypoglycemia results from an imbalance between glucose influx and efflux due to either excessive glucose removal from circulation, deficient glucose delivery into circulation, or both. Hypoglycemia in diabetes is usually the result of the interplay of therapeutic hyperinsulinemia and compromised defenses against falling glucose levels resulting in hypoglycemia-associated autonomic failure, including defective glucose counterregulation and impaired awareness of hypoglycemia. An attenuated sympathoadrenal response to falling glucose levels is induced by recent antecedent hypoglycemia, sleep, or prior exercise, and reversible by short-term avoidance of hypoglycemia. Iatrogenic hypoglycemia is associated with morbidity and fatality in type 1 and type 2 diabetes mellitus. Hypoglycemic risk reduction in those with diabetes at risk of hypoglycemia includes addressing the issue, aggressive glycemic therapy, and considering conventional risk factors and those indicative of hypoglycemia-associated autonomic failure. In the absence of diabetes, hypoglycemia in ill or medicated people can be caused by drugs, critical illnesses, endocrine deficiencies, or non–islet cell tumors; in seemingly well people, it may be caused by endogenous hyperinsulinism or various accidental, surreptitious, or malicious mechanisms. In children, it may also be the result of abnormalities in enzyme deficiencies that are key for the metabolism of fuel substrates that will contribute to abnormalities in glucose production and utilization. The decision to evaluate a nondiabetic person systematically is recommended only for those in whom Whipple triad can be documented. Short-term treatment of hypoglycemia includes oral carbohydrates or parenteral glucagon or glucose; long-term treatment requires correction of the hypoglycemic mechanism.

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