Hypoglycemia Clinical and Laboratory Diagnosis

Confirmation of Hypoglycemia

The presence of hypoglycemia is often suspected on the basis of a history compatible with neurogenic or neuroglycopenic symptoms. Although sometimes compelling, the history is more often only suggestive, since such symptoms are common in a variety of other disorders. Thus the diagnosis of hypoglycemia is suspected much more often than it is confirmed. Symptoms of hypoglycemia usually occur more than several hours after meals, often after exercise. However, as noted above, patients with disorders that cause fasting hypoglycemia, may also develop hypoglycemia within several hours of a meal. Occasionally, a hypoglycemic disorder is first suspected because of a low glucose level in a plasma sample obtained for other reasons.

Once suspected, the diagnosis of hypoglycemia is most convincingly established when it is based on Whipple's triad: symptoms consistent with hypoglycemia, a concomitant low plasma glucose concentration, and relief of symptoms after the glucose level is raised to normal. The diagnosis of a hypoglycemic disorder is seldom tenable in the absence of consistent symptoms.

Patients with fasting hypoglycemia may have plasma glucose levels below 45 mg/dl (2.5 mmol/L) after a 10- to 12-hour overnight fast, especially with repeated measurements. Thus the first diagnostic step in suspected fasting hypoglycemia is to measure the plasma glucose concentration after an overnight fast, on several days if necessary. A value less than 45 mg/dl documents the presence of fasting hypoglycemia. If plasma glucose level is greater than 45 mg/dl after an overnight fast, the fast should be prolonged until symptomatic hypoglycemia with a plasma glucose level less than 45 mg/dl occurs, or for a maximum of 72 hours. Plasma glucose should be measured at least every 4 hours (more frequently as plasma glucose level falls) and when symptoms occur. Bedside glucose monitoring devices may be used for rapid estimation but are not accurate enough for definitive diagnosis; laboratory measurements should be performed. Symptomatic hypoglycemia usually occurs within the first 24 hours of a diagnostic fast in affected patients. A period of exercise at the end of a prolonged fast may precipitate hypoglycemia in an affected patient, in contrast to the normal stability of plasma glucose during exercise.

When symptomatic hypoglycemia with a plasma glucose level less than 45 mg/dl occurs, certain tests should be performed to distinguish among possible causes. Plasma insulin and C-peptide should be measured, preferably on several samples, before the fast is ended, and a plasma or urine assay for sulfonylureas should be performed.

Failure of the plasma glucose concentration to fall below 50 mg/dl during a prolonged fast, particularly if a period of exercise is included, excludes the diagnosis of fasting hypoglycemia. In men, fasting plasma glucose values below 50 mg/dl document the presence of fasting hypoglycemia. The same statement cannot be made for women or children, in whom plasma glucose concentrations commonly fall below 50 mg/dl in the absence of symptoms during a prolonged fast. If values below 50 mg/dl are associated with unequivocal symptoms in a woman or a child, fasting hypoglycemia has been documented. If not, convincing biochemical evidence is required for diagnosis of a fasting hypoglycemic disorder (see later discussion).