Hypoglycemia laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

Laboratory investigations of hypoglycemia depend on many tests: plasma glucose should be <55 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, 24-hour fasting glucose level and identifying the cause after that.

Laboratory Findings

Defining Hypoglycemia

Hypoglycemia can't be diagnosed only by measuring blood glucose level because it is misleading maneuver with high false positive results. The measurement should be repeated using a collection tube that contains an inhibitor of glycolysis and processing should not be delayed.

So, the following 3 characteristics should be present to diagnose hypoglycemia, which is called Whipple's triad and includes:

• Symptoms of hypoglycemia
• A low plasma glucose concentration correlated with symptoms
• Correction of glucose level relieves symptoms

The strategy is to seek Whipple's triad under conditions in which hypoglycemia would be expected:

• If the symptoms occur in the fasting state, that evaluation should be performed during fasting.
• If there is a compelling history of postprandial symptoms, it is reasonable to seek Whipple's triad with frequent, timed plasma glucose measurements and recording of any symptoms after a mixed meal.
• All of the following should be measured:
  • Glucose: plasma glucose should be <55 mg/dL.
  • Insulin
  • C-peptide
  • Proinsulin
  • Sulfonylurea and meglitinide screen
  • Beta-hydroxybutyrate

Fasting evaluation	Mixed-meal evaluation
If prolonged fasting may result in an episode of symptomatic hypoglycemia, plasma glucose should be measured repeatedly during fasting. If symptoms occur and hypoglycemia is documented, the other tests mentioned above should be performed. If the results are equivocal so the patient needs another confirmatory test such as the 72-hour fast.	If symptoms appear within 5 hours after meals, we should suspect postprandial hypoglycemia. Recurrent sampling before and after meals for the following 5 hours will help diagnosis; If severe symptoms occur, the samples for glucose should be analyzed. If Whipple's triad is demonstrated, sulfonylureas, meglitinides, and antibodies to insulin should also be measured.

24-hour fasting

• Increased release of glucagon, epinephrine, and cortisol is the most important factors that keep blood glucose concentrations from falling during fasting.
• Gluconeogenesis is the most important factor of glucose production after a prolonged fast.
• If there is a high level of insulin, gluconeogenesis will be inhibited causing hypoglycemia during fasting.

• The fasting is ended when:
  • Seventy-two hours have passed
  • Plasma glucose concentration is ≤45 mg/dL
  • Patient has symptoms or signs of hypoglycemia
• The precise level of glucose considered low enough to define hypoglycemia is dependent on:
  • Measurement method
  • Age of the person
  • Presence or absence of effects
  • The purpose of the definition

Identifying the cause

After confirmation of hypoglycemia. Physicians should have history, signs and laboratory results sufficient to help them to identify the cause of hypoglycemia:

	Plasma insulin	C-peptide	proinsulin	Sulfonylurea in plasma	insulin or insulin receptor antibodies	Postprandial symptoms	Fating symptoms
Insulinoma	high	high	high	-	-	-	+
Oral hypoglycemics	high	high	high	+	-	-	-
Autoimmune hypoglycemia	high	high	high	-	+	-	-
NIPHS*	high	high	high	-	-	+	-
Exogenous insulin	high	low	low	-	-	-	-
Non-islet cell tumors	low	low	low	-	-	-	-

*(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome

Neonatal hypoglycemia:

Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases:

• Hypoglycemia that requires prolonged high rates of dextrose infusion
• Persistent hypoglycemia
• Neurologic symptoms
• History or physical findings suggestive of metabolic disease

What to measure?

• Measure plasma insulin, plasma C-peptide and beta-hydroxybutyrate
• Blood pH, bicarbonate, and lactate
• Free fatty acids, acylcarnitine profile, plasma free and total carnitine levels

• Growth hormone and Cortisol.
• Urine organic acids and serum amino acids.

Surveys of healthy children and adults show that plasma glucose below 60 mg/dL or above 100 mg/dL are found in less than 5% of samples after an overnight fast.

In infants and young children, up to 10% have been found to be below 60 mg/dL after an overnight fast. As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people.

In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease.