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Hypoglycemia in adults without diabetes mellitus: Diagnostic approach

F John Service, MD, PhD
Section Editor
Irl B Hirsch, MD
Deputy Editor
Jean E Mulder, MD


Hypoglycemia is an uncommon clinical problem in patients not being treated for diabetes mellitus. It can occur in the fasting or postprandial state. In any case of hypoglycemia, regardless of the cause, the diagnosis can usually be established by appropriate blood tests at the time of the spontaneous occurrence of hypoglycemia, if such an event occurs in the presence of medical personnel (table 1).

If the patient is not symptomatic when seen, the diagnostic strategy is to replicate conditions in which hypoglycemia would be expected if a hypoglycemic disorder exists. A prolonged supervised fast, which can last as long as 72 hours, has been the best established and probably most reliable test for the evaluation of hypoglycemia occurring in the food-deprived state. For patients with postprandial hypoglycemia, however, a mixed meal test is the preferred provocative procedure.

This topic will review the approach to the nondiabetic patient with hypoglycemia. The clinical manifestations, diagnosis, and causes of hypoglycemia, in general, are discussed separately (table 2 and table 3). The evaluation and management of hypoglycemia in patients with drug-treated diabetes mellitus is also reviewed separately. (See "Hypoglycemia in adults: Clinical manifestations, definition, and causes" and "Diagnostic dilemmas in hypoglycemia: Illustrative cases" and "Management of hypoglycemia during treatment of diabetes mellitus".)


The presence of a hypoglycemic disorder in a person without diabetes should not be suspected solely on the basis of a low plasma glucose concentration [1,2], as this observation is necessary but insufficient for a diagnosis and in some cases may be misleading. Only those patients in whom Whipple's triad is documented require evaluation and management of hypoglycemia. Given documentation of Whipple's triad, detailed laboratory evaluation is usually required in a healthy-appearing patient, whereas hypoglycemia may be readily recognized as part of the underlying illness or its treatment in an ill or medicated patient (table 2). (See "Hypoglycemia in adults: Clinical manifestations, definition, and causes", section on 'Clinical manifestations'.)

Whipple's triad includes the following:


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Literature review current through: Sep 2016. | This topic last updated: Aug 4, 2015.
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