What labs can assess if the pancreas is producing insulin?

Laboratory Tests to Assess Pancreatic Insulin Production

C-peptide measurement is the most reliable laboratory test to assess if the pancreas is producing insulin, as it is secreted in equimolar amounts to endogenous insulin but has a more constant excretion rate and longer half-life. 1

Primary Assessment Methods

C-peptide Testing

• Fasting C-peptide: Most commonly used baseline measurement

  • Normal range: Typically 0.5-2.0 nmol/L (varies by laboratory)
  • Values <0.2 nmol/L suggest significant insulin deficiency consistent with type 1 diabetes 1, 2
  • Values >0.6 ng/mL with hypoglycemia may indicate insulinoma 1

• Stimulated C-peptide: More sensitive than fasting measurements

  • Glucagon stimulation test: Preferred method due to balance of sensitivity and practicality 2
    • Administer 1mg glucagon IV/IM and measure C-peptide at 0 and 6 minutes
  • Mixed meal tolerance test: Alternative stimulation method
  • C-peptide/glucose ratio (CGR): Useful for estimating insulin secretory capacity 3
    • Helps discriminate between insulin deficiency and hypersecretion

Additional Insulin Production Tests

• Insulin levels: Less reliable than C-peptide due to:

  • Shorter half-life
  • Variable hepatic extraction
  • Greater fluctuations in peripheral levels 1, 2
  • For suspected insulinoma: Insulin >3 mcIU/mL (usually >6 mcIU/mL) when fasting glucose <55 mg/dL 1

• Proinsulin levels: Useful in specific scenarios

  • Values >5 pmol/L with blood glucose <2.5 mmol/L are diagnostic for endogenous hyperinsulinism 4
  • Values >22 pmol/L with blood glucose 2.5-3.3 mmol/L suggest hyperinsulinism 4

Clinical Applications

Differentiating Diabetes Types

• C-peptide helps distinguish between type 1 and type 2 diabetes in ambiguous cases 1
  • Type 1: Typically low or undetectable C-peptide (<0.2 nmol/L)
  • Type 2: Usually normal or elevated C-peptide
  • Important when patients present with atypical features or in ketoacidosis with type 2 phenotype

Diagnosing Insulinoma

• Diagnostic triad for insulinoma includes: 1
  1. Insulin level >3 mcIU/mL (usually >6 mcIU/mL)
  2. C-peptide concentrations ≥0.6 ng/mL
  3. Proinsulin levels ≥5 pmol/L
  • All measured when fasting blood glucose is <55 mg/dL

Assessing Pancreatic Function in Chronic Pancreatitis

• Patients with chronic pancreatitis often show: 5
  • Lower C-peptide levels despite normal fasting glucose
  • Altered insulin/C-peptide ratio due to reduced insulin metabolism

Important Considerations

Testing Conditions

• Ensure proper fasting status (8-12 hours) for accurate interpretation
• Document concurrent glucose level when measuring C-peptide
• For fasting C-peptide measurement for insulin pump coverage, ensure fasting plasma glucose is ≤220 mg/dL (12.5 mmol/L) 1

Potential Pitfalls

• C-peptide levels can be falsely low in renal failure (reduced clearance)
• Insulin autoantibodies may interfere with insulin assays but not C-peptide
• Surreptitious insulin administration will show low C-peptide with high insulin
• Proinsulin cross-reactivity may affect some older insulin assays

Clinical Value in Specific Populations

• C-peptide testing is most valuable in patients with: 6
  • Low BMI
  • High blood glucose levels
  • Long-standing diabetes

When to Order These Tests

• When differentiating between type 1 and type 2 diabetes is clinically important
• When evaluating suspected insulinoma or other causes of hypoglycemia
• When assessing residual beta-cell function in long-standing diabetes
• When required by payers for coverage of insulin pump therapy 1

For routine diabetes management and diagnosis, these specialized tests are not generally recommended unless clinically indicated for specific diagnostic dilemmas 1.