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Hypoglycemia

Hypoglycemia is defined by the presence of Whipple’s triad: plasma glucose concentration less than 50 mg/dL, symptoms of nervousness, anxiety and sweating, and relief of symptoms with administration of glucose. It occurs infrequently in hospitalized patients. The most common causes of hypoglycemia in inpatients are diabetes mellitus, renal failure, liver disease, infection, pregnancy, metastatic cancer, and burns.

Hypoglycemia is also rare in outpatients. The best way to diagnose this condition is to instruct the patient to eat a meal similar to the one that produces symptoms and then have their blood drawn for a plasma glucose level when they become symptomatic. If plasma glucose is not <50 mg/dL, then the person does not have hypoglycemia.

If a person has an abnormal screening test, they should be further evaluated with a 72 hour fast unless an obvious cause is indicated in the medical history, physical exam or laboratory tests. The 72 hour fast attempts to document Whipple’s triad under controlled conditions. This test is difficult to perform correctly. Criteria for discontinuing the fast are strict: blood glucose level must be lower than 45 mg/dL and the patient must be symptomatic. All nonessential medications must be discontinued and only water, black decaffeinated coffee, and diet sugar-free sodas can be consumed.

The 72 hour fast is a sensitive test for insulinoma. Most patients with insulinoma become hypoglycemic within 48 hours. Patients who are abusing oral antihypergycemic agents (OAA) will not become hypoglycemic during the test.

The majority of otherwise healthy hypoglycemic individuals will be found to have insulin mediated hypoglycemia, either due to inappropriate insulin production, insulin injection, or ingestion of OAA. At the time of true hypoglycemia, they should be tested for insulin, C-peptide, proinsulin and OAA. Insulin mediated hypoglycemia is recognized if insulin is detectable (>3 mU/mL with chemiluminescent methods) at the time of hypoglycemia. Interpretation of test results is shown in the table below.

Disorder

Insulin

C-pep

Pro

OAA

Insulinoma

Inc

Inc

Inc

ND

Insulin injection

Inc

Dec

Dec

ND

OAA

Inc

Inc

Inc

Pos

Non-insulin mediated

Dec

Dec

Dec

ND

The normal response to hypoglycemia is suppression of insulin secretion. Insulin is synthesized in the pancreas as proinsulin and this protein is cleaved to form insulin and C peptide. Both are secreted into the circulation simultaneously.

  • If endogenous insulin is being hypersecreted, both insulin and C peptide will be inappropriately high in the presence of a low blood glucose level.
  • If exogenous insulin is being administered in quantities sufficient to cause hypoglycemia, islet cell secretion of endogenous insulin and C peptide will be suppressed.
  • OAA ingestion gives the same biochemical picture as an insulinoma, causing endogenous hyperinsulinemia by releasing insulin from the pancreas. An OAA screen should be performed to rule out this etiology.

Cases of factitious hypoglycemia have several common clinical characteristics:

1.The patient is usually female

2.The patient or their spouse is a health professional

3.The patient has a close relative with diabetes treated with OAA

4.The patient has an unusual affect or psychiatric history

5.The patient has an abrupt onset of severe symptoms without previous milder symptoms

6.The 72 hour fasting test does not produce hypoglycemia

Reference value is 65 - 110 mg/dL. Values <50 or >500 mg/dL are considered critical values. Low values detected with a glucose meter should be confirmed in the central laboratory.

Specimen requirement is one grey top (potassium oxalate, sodium fluoride) tube of blood.

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