What is the significance of C (connecting) peptide levels in insulin-dependent diabetes mellitus?

Significance of C-peptide Levels in Insulin-Dependent Diabetes Mellitus

C-peptide levels in insulin-dependent diabetes mellitus (type 1 diabetes) serve as a critical marker of residual beta-cell function, with low or undetectable levels indicating advanced disease requiring insulin for survival. 1, 2

What is C-peptide?

• C-peptide (connecting peptide) is a polypeptide produced during insulin biosynthesis
• It is cleaved from proinsulin in pancreatic beta cells and secreted in equimolar amounts with insulin
• Unlike insulin, C-peptide experiences minimal hepatic extraction, making it a more reliable marker of endogenous insulin production 3

Clinical Significance in Type 1 Diabetes

Diagnostic Value

• Low or undetectable C-peptide levels indicate little to no endogenous insulin secretion in advanced type 1 diabetes 1
• C-peptide levels help differentiate between types of diabetes:
  • <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 2

Disease Progression Marker

• C-peptide levels decline progressively in type 1 diabetes as autoimmune destruction of beta cells continues
• The rate of beta-cell destruction varies:
  • Rapid in children and infants
  • Slower in adults, who may retain sufficient beta-cell function to prevent ketoacidosis for years 1
• At later stages of disease, little or no insulin secretion is manifested by low or undetectable plasma C-peptide 1

Treatment Implications

• Patients with very low C-peptide (<0.6 ng/mL) require basal-bolus insulin therapy for survival 2
• Preservation of even small amounts of C-peptide is associated with:
  • Better glycemic control
  • Reduced risk of hypoglycemia
  • Lower risk of microvascular complications 2, 4
• C-peptide measurement helps determine absolute insulin requirement regardless of apparent diabetes etiology 5

Clinical Applications

1. Diabetes Classification:

   • Helps distinguish between type 1 and type 2 diabetes, especially in ambiguous cases
   • Most valuable 3-5 years after diagnosis when persistence of substantial insulin secretion suggests type 2 or monogenic diabetes 5

2. Treatment Decisions:

   • Absent C-peptide confirms absolute insulin requirement
   • Guides insulin regimen intensity and appropriateness of type 1 diabetes management strategies 2, 5

3. Monitoring Disease Progression:

   • Tracks remaining beta-cell function over time
   • Helps predict future insulin requirements 6

4. Research Applications:

   • Primary outcome measure in clinical trials aiming to preserve beta-cell function
   • More sensitive than HbA1c for assessing interventions targeting the disease process 7

Measurement Considerations

• C-peptide should be measured under standardized conditions
• Not recommended within 2 weeks after a hyperglycemic emergency
• Should be interpreted in context of simultaneous glucose levels 2
• Modern assays can detect very low levels relevant to clinical decision-making 6

Clinical Implications

• Even modest preservation of C-peptide secretion is associated with clinical benefits
• Early intervention with insulin may help preserve remaining beta-cell function
• Patients with undetectable C-peptide require more vigilant monitoring for hypoglycemia 2
• C-peptide deficiency may contribute to development of diabetic complications beyond insulin deficiency 4

C-peptide measurement provides valuable information about residual beta-cell function in insulin-dependent diabetes, guiding treatment decisions and helping predict long-term outcomes related to glycemic control and complications.