Management of Decreased C-Peptide Levels in Insulin-Treated Patients
For patients with diabetes on insulin therapy who have decreased C-peptide levels, continue intensive insulin therapy regardless of C-peptide status, as the presence or absence of measurable C-peptide does not correlate with response to intensive insulin treatment. 1
Understanding C-Peptide in Clinical Context
C-peptide is secreted equimolarly with insulin from pancreatic beta cells and serves as the most reliable measure of endogenous insulin secretion. 2, 3 Unlike insulin, C-peptide experiences minimal hepatic first-pass clearance, making it an accurate marker of beta-cell function. 2, 4
Low or undetectable C-peptide (<0.4 nmol/L or <0.6 nmol/L depending on assay) indicates absolute insulin deficiency and confirms the need for lifelong insulin therapy. 1, 5
Clinical Implications for Insulin Therapy
Key Guideline Principle
The 2023 American Diabetes Association Standards of Care explicitly states that for people with diabetes judged to be clinically insulin deficient who are treated with intensive insulin therapy, the presence or absence of measurable C-peptide levels does not correlate with response to therapy. 1 This is a critical point that directly addresses your question.
Insulin Delivery Options Regardless of C-Peptide Status
For patients with low C-peptide on insulin, multiple evidence-based options exist:
Automated insulin delivery systems should be offered to all adults with insulin deficiency (low C-peptide), as they improve glycemic control and quality of life while minimizing hypoglycemia risk. 1
Insulin pumps (continuous subcutaneous insulin infusion) can be used safely and effectively regardless of C-peptide levels, with no data suggesting that C-peptide measurement predicts success with pump therapy. 1
Multiple daily injections with basal and prandial insulin analogs remain the standard alternative, with analogs preferred over human insulins to minimize hypoglycemia. 1
Risk Factors and Monitoring Considerations
Hypoglycemia Risk Profile
Patients with low C-peptide face distinct challenges:
Residual C-peptide secretion reduces glycemic variability and risk of severe hypoglycemia by 6-20 fold; absence of C-peptide increases vulnerability to hypoglycemia and requires more intensive monitoring. 1
Loss of all measurable C-peptide typically occurs within 10-15 years after type 1 diabetes diagnosis, making hypoglycemia avoidance more challenging in long-standing disease. 1
Patients with absent C-peptide experience higher glycemic variability and more difficult glycemic control, particularly when burdened with comorbidities. 1
Enhanced Monitoring Requirements
Early use of continuous glucose monitoring is recommended for all patients with insulin deficiency (low C-peptide) to improve glycemic outcomes, quality of life, and minimize hypoglycemia. 1
Sensor-augmented pump therapy with automatic low glucose suspend should be considered to prevent/mitigate hypoglycemia episodes in patients with absent endogenous insulin secretion. 1
Treatment Optimization Strategy
Insulin Regimen Components
For patients with low/absent C-peptide requiring intensive insulin:
Treat with continuous subcutaneous insulin infusion or multiple daily doses of prandial and basal insulin, using analog insulins preferentially. 1
Provide education on matching mealtime insulin doses to carbohydrate, fat, and protein intake, plus correction dosing based on concurrent glycemia and glycemic trends. 1
Reevaluate insulin treatment plan and insulin-taking behavior at regular intervals (every 3-6 months) to ensure achievement of individualized glycemic goals. 1
Technology Integration
Insulin pump therapy should be considered an option for any patient with insulin deficiency who is capable of safely using the device, as it may improve patient satisfaction and simplify therapy. 1
Access to insulin pump therapy should be allowed/continued in older adults with low C-peptide just as in younger patients, with no age-based restrictions. 1
Common Pitfalls to Avoid
Critical Errors in Management
Do not attempt to discontinue or reduce insulin based solely on C-peptide levels in patients already on intensive insulin therapy—C-peptide status does not predict treatment response. 1
Avoid assuming that low C-peptide automatically means poor glycemic control is inevitable; with appropriate technology (automated insulin delivery, CGM), excellent outcomes are achievable. 1
Do not withhold advanced insulin delivery technologies (pumps, automated systems) from patients with absent C-peptide, as these patients may benefit most from such interventions. 1
Hypoglycemia Prevention
Recognize that patients with absent C-peptide have lost the protective glucagon response to hypoglycemia and require more aggressive prevention strategies. 1
Implement blood glucose awareness training and educational interventions specifically designed for patients with impaired awareness of hypoglycemia, which is more common with absent C-peptide. 1
Increase frequency of blood glucose monitoring in patients at higher risk for hypoglycemia due to absent endogenous insulin secretion. 6, 7
Special Populations
Checkpoint Inhibitor-Associated Diabetes
Patients who develop checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) have absolute and fulminant beta-cell failure with persistently low C-peptide and require lifelong insulin therapy. 1
All patients with CIADM should be considered eligible for supportive technologies including insulin pumps and CGM, with starting insulin doses of 0.2-0.3 units/kg/day basal plus 0.05-0.1 units/kg/meal prandial insulin. 1
Type 2 Diabetes with Insulin Deficiency
For patients with long-standing type 2 diabetes whose C-peptide levels mimic type 1 diabetes (very low), automated insulin delivery systems may prove optimal for attaining glycemic targets while avoiding hypoglycemia. 1
Traditional insulin pumps can be considered for treatment of people with type 2 diabetes on multiple daily injections who have developed insulin deficiency, as use may improve patient satisfaction and simplify therapy. 1