Is C-peptide (connecting peptide) elevated in type 2 diabetes?

C-Peptide Levels in Type 2 Diabetes

In type 2 diabetes, C-peptide levels are typically normal or elevated, especially in early disease stages, but become disproportionately low relative to the degree of insulin resistance. 1

Understanding C-Peptide in Type 2 Diabetes

C-peptide is secreted from pancreatic β cells at an equimolar ratio to insulin, making it an excellent marker of endogenous insulin secretion. Unlike insulin, C-peptide is not extracted by the liver, allowing it to more accurately reflect insulin production 2.

The pattern of C-peptide levels in type 2 diabetes follows a distinct progression:

• Early disease stages: Insulin production (and thus C-peptide) is normal or increased in absolute terms 1
• Key characteristic: Despite normal or elevated levels, C-peptide is disproportionately low for the degree of insulin resistance 1
• Progression: Beta cell function deteriorates over time, leading to declining C-peptide levels 1

C-Peptide Measurement and Interpretation

C-peptide levels can be categorized as follows 3:

• <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

In clinical practice, C-peptide measurement is particularly valuable in:

1. Differentiating between diabetes types
2. Assessing residual beta cell function
3. Guiding treatment decisions

Clinical Implications and Treatment Considerations

Research indicates that patients with type 2 diabetes with C-peptide levels between 1.71-2.51 ng/mL show the best glycemic control and lowest incidence of diabetic kidney disease and retinopathy 4. This suggests an optimal range of beta cell function for disease management.

When C-peptide levels are:

• Very high (>2.70 ng/mL): Indicates significant insulin resistance; biguanides (metformin) are often more effective 5
• Moderate (0.58-2.70 ng/mL): Typical range for most type 2 diabetes patients 5
• Low (<0.58 ng/mL): May indicate latent autoimmune diabetes in adults (LADA) or late-stage type 2 diabetes; insulin therapy is often required 5

Important Clinical Considerations

• C-peptide levels follow a U-shaped relationship with diabetic complications - both very low and very high levels are associated with increased risk 4
• Postprandial C-peptide to glucose ratio may better reflect maximum β cell secretory capacity compared to fasting measurements 2
• C-peptide levels directly correlate with body weight in type 2 diabetes 5
• The presence of pancreatic autoantibodies is associated with lower C-peptide levels and may indicate LADA rather than typical type 2 diabetes 5

Monitoring and Follow-up

For optimal management of type 2 diabetes:

• Consider periodic reassessment of C-peptide levels to track beta cell function decline
• Adjust treatment strategies based on C-peptide trends
• Monitor more closely for complications in patients with very high or very low C-peptide levels

Remember that islet dysfunction in type 2 diabetes is not necessarily irreversible - interventions that improve glycemia can ameliorate β-cell dysfunction to some extent 1.