What is the appropriate work-up for hypoglycemia (low blood sugar)?

From the Guidelines

The workup for hypoglycemia should begin with confirming true hypoglycemia and documenting Whipple's triad, followed by a comprehensive history and laboratory tests to identify the underlying cause, as recommended by the American Diabetes Association 1. The initial evaluation should focus on confirming hypoglycemia, defined as a blood glucose level <70 mg/dL, and documenting Whipple's triad: low blood glucose, symptoms of hypoglycemia, and resolution of symptoms with glucose administration.

• A comprehensive history should be taken, focusing on medication use, especially insulin and sulfonylureas, as well as alcohol consumption, liver or kidney disease, and timing of symptoms relative to meals.
• Laboratory tests should include a basic metabolic panel, liver function tests, and measurement of insulin, C-peptide, and proinsulin levels during a hypoglycemic episode, as these tests can help identify the underlying cause of hypoglycemia, such as excess insulin production or decreased glucose production 1.
• For suspected reactive hypoglycemia, a 5-hour oral glucose tolerance test may be performed, while for fasting hypoglycemia, a supervised 72-hour fast is the gold standard diagnostic test, with blood samples collected for glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and sulfonylurea screen when glucose drops below 60 mg/dL.
• Imaging studies such as CT or MRI of the abdomen may be necessary if insulinoma is suspected, as it can help identify any underlying tumors or abnormalities that may be causing the hypoglycemia 1. Management of hypoglycemia should include immediate treatment with 15-20g of fast-acting carbohydrates, followed by a complex carbohydrate snack, and reevaluation of the treatment regimen if hypoglycemia unawareness or severe hypoglycemia occurs, as recommended by the American Diabetes Association 1.

From the FDA Drug Label

Hypoglycemia (Low Blood Sugar) is one of the most frequent adverse events experienced by insulin users. It can be brought about by: Missing or delaying meals. Taking too much insulin. Exercising or working more than usual. An infection or illness associated with diarrhea or vomiting. A change in the body's need for insulin Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease. Interactions with certain drugs, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, certain antidepressants and some kidney and blood pressure medicines. Consumption of alcoholic beverages

Hypoglycemia work-up should include checking for the above causes and monitoring blood glucose frequently, especially prior to activities such as driving.

• 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
• Treatment of mild to moderate hypoglycemia may be done by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as hard candy or glucose tablets 2. More severe hypoglycemia may require the assistance of another person or an injection of glucagon or intravenous administration of glucose at a medical facility 2.

From the Research

Hypoglycemia Work-up

• Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide 3
• Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia 3
• Episodes of hypoglycemia are associated with physical and psychological morbidity 3
• The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control 3

Diagnosis and Treatment

• Continuous glucose monitoring (CGM) is useful in detecting hypoglycemia, and hypoglycemia unawareness, monitoring response to medical therapy and for confirming cure postoperatively in patients with insulinoma 4
• Octreotide is an effective treatment of hypoglycemia in more than 50% of patients with insulinoma 5
• Detection of responsive patients was better based on a positive short test with subcutaneous octreotide than on the results of Octreoscan scintigraphy 5
• Positive anti-sst2 receptor immunostaining is associated with efficacy of octreotide treatment, but does not account for all cases of responsiveness to octreotide 5

Emergency Treatment

• Guidelines and studies recommend 15-20 g of oral glucose or sucrose, repeated after 10-15 min for treatment of the responsive adult, and 10% intravenous dextrose or 1 mg intramuscular glucagon for treatment of the unresponsive adult 6
• High-quality evidence for the management of hypoglycemia was lacking, limiting treatment recommendations 6
• Further high-quality studies are required to inform the optimum management of this frequently occurring emergency condition 6

Prevention

• Patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control, can help prevent hypoglycemia 3
• Awareness of the potential dangers of hypoglycemia is fundamental to the optimal management of diabetes 7
• Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention and treatment 7