What is the appropriate workup for hypoglycemia?

Appropriate Workup for Hypoglycemia

The appropriate workup for hypoglycemia should begin with documenting Whipple's triad (symptoms consistent with hypoglycemia, low plasma glucose concentration, and resolution of symptoms after glucose is raised) before proceeding with further evaluation to determine the underlying cause. 1

Classification of Hypoglycemia

• Hypoglycemia alert value: blood glucose ≤3.9 mmol/L (70 mg/dL) 2
• Clinically significant hypoglycemia: blood glucose <3.0 mmol/L (54 mg/dL) 2
• Severe hypoglycemia: no specific glucose threshold but defined as severe cognitive impairment requiring external assistance for recovery 2

Initial Assessment

• Confirm hypoglycemia with blood glucose measurement immediately when symptoms are suspected 2
• If glucose testing is not immediately available, proceed with treatment and confirm retrospectively 2
• Document symptoms (shakiness, irritability, confusion, tachycardia, hunger) and their resolution with treatment 2
• Evaluate for precipitating factors:
  • Medications (insulin, sulfonylureas, other glucose-lowering drugs) 2, 3
  • Missed or delayed meals 2
  • Exercise (recent or ongoing) 2
  • Alcohol consumption 3
  • Critical illness 1, 4

Laboratory Evaluation During Hypoglycemic Episode

For non-diabetic patients or when the cause is unclear, obtain the following during a hypoglycemic episode:

• Plasma glucose 1, 5
• Insulin 1, 5
• C-peptide 1, 5
• Proinsulin 1
• Beta-hydroxybutyrate 1
• Screening for oral hypoglycemic agents 1
• Insulin antibodies 1

Diagnostic Testing Based on Clinical Presentation

• For fasting hypoglycemia: Consider 72-hour supervised fast 5
• For postprandial hypoglycemia: Consider mixed meal test 5
• For suspected insulinoma or endogenous hyperinsulinism: Measure insulin, C-peptide, and proinsulin during hypoglycemic episode 1, 5
• For suspected factitious hypoglycemia: Test for presence of oral hypoglycemic agents and insulin antibodies 1, 4

Evaluation of Specific Etiologies

• In patients with diabetes:

  • Review medication regimen (insulin doses, timing, type) 3
  • Assess patterns of food intake and exercise 3
  • Evaluate for impaired counterregulatory responses 3
  • Consider continuous glucose monitoring for patients with recurrent hypoglycemia 6

• In patients without diabetes:

  • Evaluate for critical illness (hepatic, renal, cardiac failure) 1, 4
  • Screen for hormone deficiencies (adrenal insufficiency, growth hormone deficiency) 1, 5
  • Consider non-islet cell tumors 1, 5
  • Evaluate for post-bariatric surgery hypoglycemia 5
  • Consider autoimmune hypoglycemia (insulin antibodies) 5, 4

Management Protocol

• Immediate treatment for conscious patients: 15-20g oral glucose (preferred) or any carbohydrate containing glucose 2, 7
• For cognitive impairment: 20-40 ml of 50% glucose solution IV or glucagon 0.5-1.0 mg IM 2
• Recheck blood glucose 15 minutes after treatment 2, 7
• If hypoglycemia persists, repeat treatment 2, 7
• Once blood glucose normalizes (>3.9 mmol/L), provide starchy or protein-rich foods if next meal is more than one hour away 2

Follow-up and Prevention

• Investigate the cause of hypoglycemia and adjust medications as needed 2
• For patients with hypoglycemia unawareness, raise glycemic targets for at least several weeks to reverse unawareness 2
• Consider relaxing glucose control targets in patients with cognitive impairment 2
• Monitor for hypoglycemia-associated cardiovascular and cerebrovascular diseases 2
• Advise regular self-monitoring of glucose, with continuous monitoring if possible 2, 6
• Provide diabetes education and instruct patients to carry emergency diabetes identification 2

Special Considerations

• For hospitalized patients, implement a standardized hypoglycemia treatment protocol 2
• Review treatment regimens when blood glucose <70 mg/dL (3.9 mmol/L) is documented 2
• Consider predictive algorithms to identify patients at high risk for inpatient hypoglycemia 2
• For patients with recurrent hypoglycemia, evaluate for hypoglycemia unawareness 2, 3