In a patient who developed diabetes after an episode of acute pancreatitis and has a C‑peptide level of 10.7 ng/mL, what does this level indicate and what is the appropriate initial management?

C-Peptide 10.7 ng/mL in Post-Pancreatitis Diabetes

A C-peptide level of 10.7 ng/mL (>3,200 pmol/L) is markedly elevated and indicates substantial preserved beta-cell function, strongly suggesting Type 2 diabetes rather than Type 1 or Type 3c diabetes, and initial management should focus on non-insulin therapies such as metformin with lifestyle modification. 1

Interpretation of the C-Peptide Level

Classification Based on C-Peptide Thresholds

• Your patient's C-peptide of 10.7 ng/mL (approximately 3,240 pmol/L) far exceeds the >600 pmol/L (>1.8 ng/mL) threshold that the American Diabetes Association uses to classify Type 2 diabetes. 1

• According to the 2025 ADA Standards of Care, C-peptide >600 pmol/L indicates Type 2 diabetes regardless of testing circumstances, and values this high definitively rule out Type 1 diabetes or severe insulin deficiency. 1

• C-peptide <200 pmol/L (<0.6 ng/mL) would indicate Type 1 diabetes or checkpoint inhibitor-related autoimmune diabetes with absolute beta-cell failure. 1

• The intermediate range of 200-600 pmol/L (0.6-1.8 ng/mL) is typically consistent with Type 1 diabetes, MODY, or long-standing insulin-treated Type 2 diabetes. 1

Post-Pancreatitis Context

• While Type 3c diabetes (diabetes of the exocrine pancreas) can occur after acute pancreatitis, it is characterized by reduced insulin and C-peptide secretion, not elevated levels. 2

• Research demonstrates that patients with diabetes following severe acute pancreatitis have lower C-peptide AUC compared to Type 2 diabetes controls, particularly at 90 and 120-minute timepoints during oral glucose tolerance testing. 2

• Paradoxically, some patients after acute pancreatitis with normal glucose tolerance actually show elevated insulin and C-peptide responses compared to controls, maintained at the cost of increased insulin secretion to compensate for insulin resistance. 3

• Your patient's markedly elevated C-peptide suggests insulin resistance with compensatory hyperinsulinemia, the hallmark of Type 2 diabetes, rather than the beta-cell destruction seen in Type 3c diabetes. 2

Initial Management Approach

Non-Insulin Therapy as First-Line

• The ADA flowchart explicitly states that with C-peptide >600 pmol/L and features of Type 2 diabetes (which includes post-pancreatitis presentation without ketoacidosis), a trial of non-insulin therapy is appropriate. 1

• Features supporting Type 2 diabetes classification include: BMI ≥25 kg/m², absence of weight loss, absence of ketoacidosis, less marked hyperglycemia, and longer duration of milder symptoms prior to presentation. 1

Specific Treatment Recommendations

• Initiate metformin as first-line therapy unless contraindicated, combined with lifestyle modification including dietary counseling and physical activity. 1

• Target glucose range of 5-10 mmol/L (90-180 mg/dL) is reasonable for most patients, with more flexible targets if elderly or experiencing frequent hypoglycemia. 1

• If blood glucose persistently ≥15 mmol/L or HbA1c ≥9%, seek endocrinology consultation as insulin may be required despite preserved C-peptide. 1

Monitoring Strategy

• Provide glucometer for daily self-monitoring given the recent diagnosis and need to assess glycemic response to therapy. 1

• Recheck HbA1c in 3 months to assess treatment response and guide therapy intensification if needed. 1

• Monitor for development of exocrine pancreatic insufficiency with fecal elastase testing if symptoms of malabsorption develop (steatorrhea, weight loss), as this can coexist with post-pancreatitis diabetes. 1

Critical Pitfalls to Avoid

• Do not assume all post-pancreatitis diabetes is Type 3c requiring insulin—C-peptide levels guide classification and treatment. 1, 2

• Do not test C-peptide within 2 weeks of a hyperglycemic emergency or diabetic ketoacidosis, as results will be unreliable. 1

• Misclassification occurs in 40% of adults with new diabetes, so objective C-peptide measurement prevents inappropriate insulin initiation in patients with preserved beta-cell function. 1

• Most new diabetes cases following severe acute pancreatitis are only identified at the 120-minute timepoint of oral glucose tolerance testing, so fasting glucose alone may miss the diagnosis. 2

• The prevalence of diabetes/prediabetes following severe acute pancreatitis is 54%, with 38.5% newly diagnosed, emphasizing the importance of screening all post-pancreatitis patients. 2