From the Guidelines
Laboratory workup for hypoglycemic episodes should include immediate tests during the hypoglycemic event, such as serum glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and sulfonylurea screen, as well as subsequent investigations like comprehensive metabolic panel, complete blood count, hemoglobin A1C, cortisol level, and thyroid function tests to determine the underlying cause 1. When evaluating hypoglycemic episodes, it is crucial to consider the classification of hypoglycemia, which includes level 1, level 2, and level 3 hypoglycemia, as outlined in the 2023 standards of care in diabetes 1. Key points to consider in the laboratory workup include:
- Serum glucose levels to confirm hypoglycemia, typically <70 mg/dL
- Insulin, C-peptide, and proinsulin levels to distinguish between endogenous hyperinsulinism and exogenous insulin administration
- Beta-hydroxybutyrate and sulfonylurea screen to evaluate for non-insulin mediated causes
- Comprehensive metabolic panel, complete blood count, hemoglobin A1C, cortisol level, and thyroid function tests to assess for organ dysfunction, endocrine disorders, or other metabolic causes In patients with suspected reactive hypoglycemia or insulinoma, additional tests like a 5-hour oral glucose tolerance test or a 72-hour supervised fast with serial glucose and insulin measurements may be necessary 1. It is essential to prioritize the most recent and highest quality study, which in this case is the 2023 standards of care in diabetes 1, to guide the laboratory workup for hypoglycemic episodes.
From the Research
Laboratory Workup for Hypoglycemic Episodes
The laboratory workup for hypoglycemic episodes involves several tests to determine the cause of hypoglycemia. According to 2, the Whipple triad should be used to confirm hypoglycemia before pursuing further diagnostic workup. The Whipple criteria include:
- Low levels of plasma glucose
- Signs or symptoms that would be expected with low levels of plasma glucose
- Improvement in those signs or symptoms when the level of plasma glucose increases
Diagnostic Approach
The initial diagnostic approach should begin by obtaining a detailed history of the nature and timing of the patient's symptoms, medications, underlying comorbid conditions, and any acute illness 2. A laboratory evaluation should be conducted at the time of the spontaneous symptomatic episode. Supervised tests such as a 72-hour fast or mixed-meal test may be needed to recreate the situation under which the patient is likely to experience symptoms.
Specific Tests
The following tests may be indicated in the laboratory workup for hypoglycemic episodes:
- Plasma insulin, C-peptide, and proinsulin levels to evaluate for inappropriate insulin secretion 3
- Plasma beta-hydroxybutyrate levels to evaluate for ketosis 3
- Continuous glucose monitoring (CGM) to evaluate for hypoglycemia and impaired hypoglycemia awareness 4
Special Considerations
In patients with diabetes, the laboratory workup for hypoglycemic episodes should also include an evaluation of the patient's diabetes management plan, including their medication regimen and glucose monitoring results 5, 4, 6. In nondiabetic patients, the laboratory workup should focus on identifying the underlying cause of hypoglycemia, such as endogenous hyperinsulinism or critical illness 2, 3.