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 is usually <55-70 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, and 24-hour fasting glucose level are another tests that are required to establish the etiology.

Laboratory Findings

Defining Hypoglycemia

The following three characteristics should be present to diagnose hypoglycemia, which is called Whipple's triad and include:

• 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 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 is usually <55-70 mg/dL.
  • Insulin
  • C-peptide
  • Proinsulin
  • Sulfonylurea and meglitinide screen
  • Beta-hydroxybutyrate

Fasting evaluation	Mixed-meal evaluation
If prolonged fasting results in an episode of symptomatic hypoglycemia, plasma glucose should be measured repeatedly during fasting. If symptoms occur and hypoglycemia is documented, other tests mentioned above should be performed. If results are equivocal, patient needs another confirmatory test, such as 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, blood glucose must be measured. 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 are 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 insulin level is high, gluconeogenesis will be inhibited causing hypoglycemia during fasting.

• The fasting should be stopped in any of the following conditions:
  • 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

Identifying the cause

The following table describes the possible causes of hypoglycemia.

	Plasma insulin	C-peptide	proinsulin	Sulfonylurea in plasma	insulin or insulin receptor antibodies	Postprandial symptoms	Fasting 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