From the Guidelines
The laboratory workup for hypoglycemia should include a comprehensive panel of tests performed during a hypoglycemic episode, ideally when blood glucose is below 70 mg/dL, as recommended by the most recent guidelines 1. This workup, often called Whipple's triad, should include measurement of:
- Plasma glucose
- Insulin
- C-peptide
- Proinsulin
- Beta-hydroxybutyrate
- Sulfonylurea levels Additionally, testing should include measurement of:
- Insulin antibodies
- Cortisol
- Growth hormone levels A 72-hour supervised fast may be necessary to provoke hypoglycemia in patients with suspected insulinoma or other causes of fasting hypoglycemia, as suggested by recent studies 1. During the fast, blood samples should be collected every 4-6 hours and when symptoms occur. A high insulin level with low C-peptide suggests exogenous insulin administration, while elevated levels of both suggest endogenous hyperinsulinism, as indicated by recent research 1. Elevated proinsulin levels may indicate insulinoma, while elevated beta-hydroxybutyrate suggests ketotic hypoglycemia. Cortisol and growth hormone measurements help rule out adrenal insufficiency and growth hormone deficiency as causes. For reactive hypoglycemia, a 5-hour oral glucose tolerance test may be more appropriate, as recommended by recent guidelines 1. These tests help differentiate between various causes of hypoglycemia, including insulinoma, factitious hypoglycemia, adrenal insufficiency, and reactive hypoglycemia, allowing for targeted treatment approaches.
From the FDA Drug Label
Hypoglycemia (Low Blood Sugar) Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:
- sweating
- drowsiness
- dizziness
- sleep disturbances
- palpitation
- anxiety
- tremor
- blurred vision
- hunger
- slurred speech
- restlessness
- depressed mood
- tingling in the hands, feet, lips, or tongue
- irritability
- lightheadedness
- abnormal behavior
- inability to concentrate
- unsteady movement
- headache
- personality changes Signs of severe hypoglycemia can include:
- disorientation
- seizures
- unconsciousness
- death
The lab work up for hypoglycemia may include blood glucose testing to determine the level of glucose in the blood.
- Frequent blood glucose monitoring is recommended, especially prior to activities such as driving, to help recognize the symptoms of hypoglycemia.
- Urine testing for glucose and ketones may also be considered in some cases. It is essential to consult a doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help avoid hypoglycemia 2.
From the Research
Lab Workup of Hypoglycemia
The lab workup of hypoglycemia typically involves measuring blood glucose levels, as well as other parameters such as insulin and C-peptide levels.
- Blood glucose levels: Measuring blood glucose levels is crucial in diagnosing hypoglycemia 3.
- Insulin and C-peptide levels: Insulin and C-peptide levels can help differentiate between different causes of hypoglycemia, such as sulfonylurea-induced hypoglycemia or insulinoma 4, 5, 6.
Diagnostic Criteria
The Whipple triad is used to confirm hypoglycemia, which includes:
- 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 3
Laboratory Evaluation
A laboratory evaluation should be conducted at the time of the spontaneous symptomatic episode, and may include:
- Blood glucose measurement
- Insulin and C-peptide levels
- 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 3
Causes of Hypoglycemia
Spontaneous hypoglycemia can be caused by conditions that cause endogenous hyperinsulinism, including:
- Insulinoma
- Postbariatric hypoglycemia
- Noninsulinoma pancreatogenous hypoglycemia
- Critical illness
- Hepatic or renal dysfunction
- Hormonal deficiency
- Non-diabetes-related medications
- Non-islet cell tumors 3