Diagnostic Test Accuracy of Urine C-peptide Creatinine Ratio for the Correct Identification of the Type of Diabetes: A Systematic Review

Abstract

Objective: To examine the accuracy of urine c-peptide creatinine ratio (UCPCR) for identifying the type of diabetes in appropriate clinical settings. Design: Systematic review of test accuracy studies on patients with different forms of diabetes. Data sources: Medline, Embase and Cochrane library databases from 1 January 2000 to 15 November 2020. Eligibility criteria: Studies reporting the use of UCPCR for diagnosing patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and monogenic forms of diabetes (categorized as maturity-onset diabetes of the young [MODY]). Study selection and data synthesis: Two reviewers independently assessed articles for inclusion and assessed the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, with input from a third reviewer to reach consensus when there was a dispute. Meta-analysis was performed with the studies reporting complete data to derive the pooled sensitivity, specificity and diagnostic odds ratio (DOR), and narrative synthesis only for those with incomplete data. Results: Nine studies with 4,488 patients were included in the qualitative synthesis, while only four of these (915 patients) had complete data and were included in the quantitative synthesis. All the studies had moderate risk of bias and applicability concerns. Meta-analysis of three studies (n=130) revealed sensitivity, specificity and DOR of 84.4% (95% confidence interval [CI] 68.1-93.2%), 91.6% (82.8-96.1%) and 59.9 (32.8-106.0), respectively, for diagnosing T1DM using a UCPCR cut-off of <0.2 nmol/mmol. For participants with T2DM (three studies; n=739), UCPCR >0.2 nmol/mmol was associated with sensitivity, specificity and DOR of 92.8% (84.2-96.9%), 81.6% (61.3-92.5%) and 56.9 (31.3-103.5), respectively. For patients with MODY in the appropriate clinical setting, a UCPCR cut-off of >0.2 nmol/mmol showed sensitivity, specificity and DOR of 85.2% (73.1-92.4%), 98.0% (92.4-99.5%) and 281.8 (57.5-1,379.7), respectively. Conclusions: Based on studies with moderate risk of bias and applicability concerns, UCPCR confers moderate to high sensitivity, specificity, and DOR for correctly identifying T1DM, T2DM and monogenic diabetes in appropriate clinical settings. Large multinational studies with multi-ethnic participation among different age groups are necessary before this test can be routinely used in clinical practice. Study registration: Protocol was registered as PROSPERO CRD42017060633.

Keywords: C-peptide; endogenous insulin reserve; maturity-onset diabetes of the young (MODY); monogenic diabetes; type 1 diabetes mellitus (T1DM); type 2 diabetes mellitus (T2DM); urine C-peptide creatinine ratio (UCPCR).

Figure 1:. Study flow diagram

Figure 2:. The risk of bias and applicability concerns summary: Authors' judgements about each domain for each included study^,,,,–

Figure 3:. The risk of bias and applicability concerns graph: Authors' judgements about each domain for each included study

Figure 4:. (A) Forest plot for sensitivity and specificity of urine C-peptide creatinine ratio in type 1 diabetes mellitus. (B) Summary receiver operating characteristic curve for sensitivity and specificity of urine C-peptide creatinine ratio in type 1 diabetes mellitus^,,

Figure 5:. (A) Forest plot for sensitivity and specificity of urine C-peptide creatinine ratio in type 2 diabetes mellitus. (B) Summary receiver operating characteristic curve for sensitivity and specificity of urine C-peptide creatinine ratio in type 2 diabetes mellitus^,,

Figure 6:. (A) Forest plot for sensitivity and specificity of urine C-peptide creatinine ratio in maturity-onset diabetes in the young. (B) Summary receiver operating characteristic curve for sensitivity and specificity of urine C-peptide creatinine ratio in maturity-onset diabetes of the young^,