Interpretation of Urine C-peptide Creatinine ratio
UCPCR is mainly to be used in patients on insulin treatment to assess endogenous insulin secretion. Its role in patients not on insulin treatment is limited.
If the result of UCPCR is out of keeping with other clinical finding then we would recommend repeating the test especially if it is unexpectedly low. Patients tipping out boric acid preservative from urine collection tube, in a sample taking more than 3 days to reach the laboratory can result in artificially low results (McDonald 2009). We are not aware of any reason for a falsely high value.
Most of the studies have been performed in patients with normal renal function (eGFR >60 mL/min/1.73 m2) but it has been validated in patients with Type 2 diabetes with moderate renal impairment (eGFR 30-60 mL/min/1.73 m2 (Bowman 2011). The test is unlikely to be appropriate in patients with severe renal impairment.
What values are expected in the different subtypes?
The urinary C-peptide creatinine ratio (UCPCR) result is best measured on a post prandial sample taken approximately two hours after a meal stimulus. The interpretation depends on the specific clinical scenario ie type of diabetes and treatment. Median and 5-95th percentile UCPCR values for non-diabetic controls, long standing Type 1 diabetes(> 5 years), Type 1 diabetes in the first five years after diagnosis, Type 2 diabetes (OHA and insulin treated) and patients with a genetic diagnosis of Maturity Onset Diabetes of the Young (MODY) are presented in table 1.
Table 1:UCPCR ranges in diabetes subtypes and controls.
Using UCPCR in clinical practice
1. Making a diagnosis in insulin treated patients
The principal role of urinary C-peptide is to identify insulin insufficiency, a feature of long term Type 1 diabetes, in insulin treated patients. We have found that > 95% Type 1 diabetes (> 5 year duration) have a UCPCR value < 0.2 nmol/mmol.
Type 1 v MODY
A cut-off UCPCR of 0.2 nmol/mmol differentiates HNF1A/4A MODY from Type 1 diabetes with a sensitivity of 97% and specificity of 96% (ROC 0.98)(Besser 2011).
Type 1 v Type 2
A cut-off of 0.2 nmol/mmol differentiates Type 2 diabetes from Type 1 diabetes with 94 % sensitivity and 94% specificity (ROC AUC 0.94) (Besser Unpublished data).
2. Monitoring the honeymoon period in Type 1 diabetes
In patients with Type 1 diabetes it is possible to measure the extent to which they are progressing through the honeymoon phase. UCPCR is highly correlated with the serum C peptide in a formal mixed tolerance test (Besser 2011)
3. Assessing in insulin treated Type 2 diabetes the extent of endogenous insulin secretion
In type 2 diabetes the endogenous insulin secretion can be measured in Type 2 diabetes. UCPCR is highly correlated with the serum C peptide in a formal mixed tolerance test (Jones 2011). Patients with a high endogenous secretion >25thcentile (Table 1) are likely be those that benefit most from metformin and other oral agents. Patients with low endogenous insulin secretion < 25th centile and particularly if <0.02 nmol/mmol.
McDonald TJ, Knight BA, Shields BM, Bowman P, Salzmann MB, Hattersley AT. Stability and Reproducibility of a Single-Sample Urinary C-Peptide/Creatinine Ratio and Its Correlation with 24-h Urinary C-Peptide. Clin Chem. 2009 Nov;55(11):2035-9. Clin Chem. 2009 Nov;55(11):2035-9. Epub 2009 Aug 27.
Bowman P, McDonald TJ, Shields BM, Knight BA, Hattersley AT. Single sample Urinary C-Peptide/Creatinine Ratio (UCPCR) is a reproducible alternative to serum C- peptide in patients with Type 2 diabetes.Diab Med
Jones AG, Besser REJ, McDonald TJ, Shields BM, Hope SV, Bowman P, Oram RA, Knight BA, Hattersley AT. Urine C-peptide creatinine ratio (UCPCR) is an alternative to stimulated serum C-peptide measurement in late onset insulin treated diabetes. Diabetic Medicine. Epub ahead of print 2011 Jan 2010
Besser REJ, Ludvigsson J, Jones AG, McDonald TJ , Shields BM, Knight BA, Hattersley AT. Urine C–peptide creatinine ratio (UCPCR) is a non-invasive alternative to the mixed meal tolerance test in children and adults with Type 1 diabetes. Diabetes Care. 2011 Mar;34(3):607-9. Epub 2011 Feb 1.
Besser REJ, Shepherd MJ, McDonald TJ, Shields BM, Knight BA, Ellard S, Hattersley AT. Urinary C-peptide creatinine ratio (UCPCR) is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration Type 1 diabetes. Diabetes Care. 2011 Feb;34(2):286-91.