What does a C-peptide (Connecting peptide) level of 9.9 ng/mL indicate?

Interpretation of C-peptide Level of 9.9 ng/mL

A C-peptide level of 9.9 ng/mL indicates significant hyperinsulinemia, which is substantially above the normal range (>1.8 ng/mL) and strongly suggests insulin resistance typical of type 2 diabetes or possibly an insulinoma. 1

Understanding C-peptide

C-peptide is produced in equal amounts to insulin and serves as the best measure of endogenous insulin secretion. Unlike insulin, C-peptide is not extracted by the liver, making it a more reliable indicator of beta cell function 2.

Normal C-peptide reference ranges:

• <0.6 ng/mL (<200 pmol/L): Type 1 diabetes pattern
• 0.6-1.8 ng/mL (200-600 pmol/L): Indeterminate status

• 1.8 ng/mL (>600 pmol/L): Type 2 diabetes pattern 1

Clinical Significance of Elevated C-peptide (9.9 ng/mL)

Primary Considerations

1. Severe Insulin Resistance

   • The markedly elevated level (9.9 ng/mL) indicates the pancreas is producing excessive insulin to overcome significant insulin resistance
   • This is consistent with advanced type 2 diabetes where beta cells are still functional but insulin effectiveness is severely compromised 3

2. Potential for Insulinoma

   • When elevated C-peptide occurs with hypoglycemia, insulinoma should be considered
   • An insulin level >3 mcIU/mL (usually >6 mcIU/mL) when blood glucose is <40-45 mg/dL, with an insulin-to-glucose ratio ≥0.3 suggests inappropriate insulin secretion 1

3. Other Conditions to Consider

   • Obesity (which increases insulin resistance)
   • Early stages of type 2 diabetes with compensatory hyperinsulinemia
   • Cushing's syndrome
   • Acromegaly

Diagnostic Algorithm

1. Check concurrent glucose level:

   • If glucose is elevated: Confirms insulin resistance pattern typical of type 2 diabetes
   • If glucose is normal or low: Consider insulinoma or other causes of inappropriate insulin secretion

2. Evaluate for metabolic syndrome markers:

   • Hypertension
   • Dyslipidemia
   • Central obesity
   • These would support the insulin resistance hypothesis

3. Consider C-peptide to glucose ratio:

   • This provides better assessment of beta cell function than C-peptide alone 4
   • Particularly useful in postprandial measurements

Management Implications

For a patient with C-peptide of 9.9 ng/mL:

1. If type 2 diabetes is confirmed:

   • Initial therapy should focus on non-insulin approaches:
     • Lifestyle modifications (diet, exercise, weight loss)
     • Insulin sensitizers (metformin as first-line)
     • Consider GLP-1 receptor agonists or SGLT2 inhibitors 1

2. If insulinoma is suspected:

   • Further diagnostic workup including:
     • 72-hour fast with serial glucose and insulin/C-peptide measurements
     • Imaging studies (CT, MRI, endoscopic ultrasound)
     • Note that proton pump inhibitors can cause spuriously elevated chromogranin A levels often measured alongside C-peptide in suspected insulinoma 1

Pitfalls and Caveats

• C-peptide testing should not be performed within 2 weeks of a hyperglycemic emergency 1
• C-peptide is not recommended for routine screening for diabetes or cardiovascular disease risk 1
• Interpretation should always include concurrent glucose levels
• Some medications may affect C-peptide levels, so a complete medication history is essential
• Kidney disease can elevate C-peptide levels due to decreased clearance 5

Regular monitoring of glycemic control with HbA1c every 3 months and periodic reassessment of C-peptide levels is recommended to track disease progression in patients with diabetes 1.