What does a low C-peptide result indicate?

Understanding Low C-peptide Results

A low C-peptide result indicates insufficient insulin production by the pancreatic beta cells, most commonly seen in type 1 diabetes where there is absolute insulin deficiency. 1, 2

Clinical Significance of Low C-peptide Levels

• C-peptide is produced in equal amounts to insulin and serves as the best measure of endogenous insulin secretion in patients with diabetes 2, 3
• Very low C-peptide levels (<80 pmol/L or <0.24 ng/mL) strongly suggest type 1 diabetes and indicate absolute insulin deficiency 1
• C-peptide values <200 pmol/L are diagnostic of type 1 diabetes according to American Diabetes Association guidelines 4, 1
• C-peptide values between 200-600 pmol/L (0.6-1.8 ng/mL) may indicate type 1 diabetes, MODY (Maturity Onset Diabetes of the Young), or insulin-treated type 2 diabetes with long duration 1
• Low C-peptide levels (<10 pmol/L) are associated with increased risk of diabetes complications including nephropathy, neuropathy, foot ulcers, and retinopathy 5

Diagnostic Algorithm for Interpreting Low C-peptide

1. Very low C-peptide (<80 pmol/L or <0.24 ng/mL)

   • Indicates absolute insulin deficiency 1
   • Diagnostic of type 1 diabetes 1
   • Requires insulin therapy for survival 1
   • No need to repeat the test at this level 1

2. Low C-peptide (80-200 pmol/L)

   • Strongly suggests type 1 diabetes 4
   • May indicate late-stage type 3c diabetes (pancreatic diabetes) 1
   • Indicates need for insulin therapy 3

3. Intermediate C-peptide (200-600 pmol/L)

   • May indicate type 1 diabetes, MODY, or insulin-treated type 2 diabetes 1
   • Further testing (autoantibodies, genetic testing) may be needed for definitive diagnosis 1

Clinical Applications of C-peptide Testing

• Differentiating between type 1 and type 2 diabetes in ambiguous cases 6, 7
• Identifying patients with LADA (Latent Autoimmune Diabetes in Adults), who initially present like type 2 but have declining C-peptide levels over time 6
• Confirming absolute insulin requirement in insulin-treated patients 3
• Identifying candidates for islet cell transplantation 6
• Predicting risk of complications and hypoglycemia 5

Important Testing Considerations

• C-peptide should only be measured in people receiving insulin treatment 1
• A random C-peptide sample within 5 hours of eating can replace formal stimulation tests 1, 4
• Do not test C-peptide within 2 weeks of a hyperglycemic emergency 1, 4
• For insulin-treated patients, C-peptide must be measured prior to insulin discontinuation 1, 4
• When interpreting results, consider concurrent glucose levels - if glucose is <4 mmol/L (<70 mg/dL), consider repeating the test 1

Clinical Implications of Low C-peptide

• Patients with low C-peptide (<200 pmol/L) require insulin therapy and should be managed as type 1 diabetes regardless of apparent etiology 3
• Low C-peptide levels are associated with poorer glycemic control (higher HbA1c) 5
• Patients with very low C-peptide are at higher risk for severe hypoglycemia 5
• Low C-peptide levels are predictive of faster progression of diabetic complications 5

Understanding C-peptide results is crucial for proper diabetes classification, treatment selection, and risk assessment, particularly in cases where the clinical presentation is ambiguous.