What is C-peptide (Connecting peptide) lab used for?

Clinical Uses of C-Peptide Laboratory Testing

C-peptide testing is primarily used to differentiate between type 1 and type 2 diabetes, assess residual beta-cell function, and guide appropriate diabetes management strategies. 1

What is C-peptide?

C-peptide (Connecting peptide) is a polypeptide that:

• Is produced in equimolar amounts to insulin during the cleavage of proinsulin in pancreatic beta cells
• Reflects endogenous insulin secretion more accurately than insulin itself because it is not extracted by the liver and has a longer half-life 2
• Serves as a reliable marker of beta-cell function 1

Primary Clinical Applications

1. Differentiating Diabetes Types

C-peptide measurement is particularly valuable in:

• Patients already on insulin therapy 1
• Cases where clinical presentation is ambiguous
• Situations where accurate classification impacts treatment decisions

C-peptide levels should be interpreted as follows:

• <0.6 ng/mL (<200 pmol/L): Type 1 diabetes pattern - requires insulin therapy
• 0.6-1.8 ng/mL (200-600 pmol/L): Indeterminate - may need additional testing
• >1.8 ng/mL (>600 pmol/L): Type 2 diabetes pattern - consider non-insulin therapies 1

2. Assessing Residual Beta-Cell Function

C-peptide testing helps:

• Determine the degree of insulin deficiency in diabetes
• Monitor disease progression over time
• Identify patients who may benefit from specific therapeutic approaches 3
• Evaluate the need for insulin therapy in patients initially diagnosed with type 2 diabetes 4

3. Identifying Special Forms of Diabetes

C-peptide is useful in diagnosing:

• LADA (Latent Autoimmune Diabetes in Adults): Clinically resembles type 2 diabetes but shows positive pancreatic autoantibodies and lower C-peptide levels 4
• MODY (Maturity Onset Diabetes of the Young): Persistence of C-peptide is an important clinical feature 4
• Factitious hypoglycemia: Differentiating between endogenous and exogenous hyperinsulinism 5

Optimal Testing Methods

The most informative C-peptide measurements include:

• Random C-peptide with concurrent glucose measurement: Collected within 5 hours of eating 1
• Stimulated C-peptide testing: Glucagon stimulation test provides good balance of sensitivity and practicality 6
• Timing considerations: Most informative after 3-5 years from diagnosis when persistence of substantial insulin secretion suggests type 2 or monogenic diabetes 1, 3

Clinical Implications of C-peptide Results

For Treatment Selection:

• Very low C-peptide (<0.6 ng/mL) indicates need for basal-bolus insulin therapy 1
• Borderline low C-peptide (0.6-1.8 ng/mL) may warrant basal insulin plus oral agents 1
• Higher C-peptide levels suggest potential benefit from non-insulin therapies 1

For Prognosis:

• Low C-peptide levels are associated with:
  • Increased risk of microvascular and macrovascular complications
  • Poorer glycemic control
  • Higher risk of severe hypoglycemia 1

Common Pitfalls and Considerations

• C-peptide results should be interpreted in conjunction with clinical presentation and other laboratory findings (especially autoantibodies)
• Renal impairment can elevate C-peptide levels due to reduced clearance
• C-peptide testing is most valuable when performed at appropriate times in the disease course:
  • Autoantibody testing is most valuable at or near diagnosis
  • C-peptide testing is most informative after several years of disease 1
• Fasting C-peptide may underestimate residual beta-cell function; postprandial or stimulated measurements may be more informative 2

By providing objective evidence of endogenous insulin secretion, C-peptide testing offers valuable insights that can guide diabetes classification, treatment selection, and long-term management strategies.