Urine C-peptide to Creatinine Ratio: Clinical Application and Utility
Urine C-peptide to creatinine ratio (UCPCR) is a reliable, non-invasive alternative to serum C-peptide measurement that accurately reflects endogenous insulin secretion and can be used to distinguish between different types of diabetes and guide treatment decisions. 1, 2
What is Urine C-peptide to Creatinine Ratio?
UCPCR is a measurement that:
- Quantifies C-peptide (a byproduct of insulin production) in urine, normalized to creatinine to account for urine concentration 1
- Provides a stable and practical alternative to serum C-peptide measurement 2
- Reflects endogenous insulin production capacity 1
How to Perform UCPCR Testing
The test involves these key steps:
- Collect a spot urine sample (first morning void or post-meal sample is preferred) 2, 3
- Measure both C-peptide and creatinine in the same sample 3
- Calculate the ratio of C-peptide to creatinine (expressed as nmol/mmol) 2
- For optimal results, collect urine 2 hours after meal stimulation 4
Collection Advantages:
- Urine C-peptide is stable for at least 3 days at room temperature when collected in boric acid preservative 3
- Can be performed in outpatient or community settings 2
- Avoids the need for venipuncture and specialized handling required for serum C-peptide 1, 4
Clinical Utility of UCPCR
1. Diabetes Classification
UCPCR effectively distinguishes between different types of diabetes:
- A UCPCR cut-off of ≥0.20 nmol/mmol has 82% sensitivity and 93% specificity for distinguishing between Type 2 diabetes and Type 1 diabetes 5
- A UCPCR cut-off of ≥0.21 nmol/mmol distinguishes between monogenic diabetes and Type 1 diabetes with 87% sensitivity and 93% specificity 5
- UCPCR is less reliable for distinguishing between monogenic diabetes and Type 2 diabetes 5
2. Assessment of Beta Cell Function
UCPCR provides valuable information about residual insulin secretion:
- UCPCR correlates strongly with stimulated serum C-peptide measurements (r = 0.82 for mixed-meal tolerance test) 2
- A 120-minute post-meal UCPCR ≥0.53 nmol/mmol has 94% sensitivity and 100% specificity for significant endogenous insulin secretion (serum C-peptide ≥0.2 nmol/L) 4
- UCPCR remains reliable even in patients with moderate renal impairment (eGFR >60 ml/min/1.73m²) 3
3. Guiding Treatment Decisions
UCPCR can inform therapeutic choices in diabetes management:
- In Type 2 diabetes, patients with UCPCR ≤0.20 nmol/mmol typically have:
- Lower BMI (22.8 kg/m² vs. 25.2 kg/m²)
- Lower serum C-peptide levels
- Higher likelihood of requiring insulin or secretagogue therapy (92% vs. 59.5%) 5
- Helps identify absolute insulin deficiency, confirming the appropriateness of Type 1 diabetes management strategies 1
Practical Considerations
Timing of Collection:
- Post-stimulation samples (2 hours after a meal) provide better discrimination than fasting samples 2, 4
- Home collection after standard meals correlates well with formal mixed-meal tolerance test results 2
Interpretation Guidelines:
- UCPCR <0.2 nmol/mmol suggests severe insulin deficiency consistent with Type 1 diabetes 5
- UCPCR >0.2 nmol/mmol suggests preserved beta cell function consistent with Type 2 or monogenic diabetes 5
- UCPCR measurements are at least as reproducible as serum C-peptide measurements (coefficient of variation: 26-28% vs. 27-38%) 3
Limitations and Caveats:
- Results may be affected by significant renal impairment (eGFR <60 ml/min/1.73m²) 2, 3
- Like albumin-to-creatinine ratio, UCPCR should be expressed as a ratio to account for urine concentration variability 6
- For optimal accuracy, confirm abnormal results with repeat testing 3
Conclusion
UCPCR represents a practical, non-invasive alternative to serum C-peptide measurement that can be easily implemented in routine clinical practice. Its stability and correlation with serum measures make it particularly valuable for diabetes classification and treatment decisions, especially when distinguishing between Type 1 and non-Type 1 diabetes.