The dual role of urinary C-peptide/creatinine ratio: predicting insulin resistance in non-diabetic adults and microvascular complications risk in patients with type 2 diabetes

TL;DR

This study shows that the urinary C-peptide/creatinine ratio can help detect insulin resistance in non-diabetic adults and predict diabetes complications in type 2 diabetes patients.

Contribution

The study demonstrates the dual utility of UCPCR as a non-invasive marker for insulin resistance and microvascular complication risk.

Findings

0hUCPCR and 2hUCPCR were higher in insulin-resistant non-diabetic individuals and lower in diabetic patients with complications.

2hUCPCR predicted microvascular complications in T2DM patients with an AUC of 0.751 and 70.7% sensitivity.

UCPCR showed strong negative correlations with insulin resistance markers and positive correlations with beta-cell function in T2DM patients.

Abstract

Insulin resistance (IR) is a key driver of type 2 diabetes mellitus (T2DM) onset, and diabetic microvascular complications (DMC) represent its poor prognosis. However, simple and non-invasive screening methods for detection of IR and DMC are limited. The urinary C-peptide/creatinine ratio (UCPCR) can be used to measure β-cell function, and we aimed to evaluate its utility as a surrogate marker for IR in non-diabetic individuals and for DMC risk in patients with T2DM.

This cross-sectional study enrolled 447 individuals (255 non-diabetic adults and 192 T2DM patients) from November 2023 to September 2025. The non-diabetic cohort was divided into IR and non-IR groups according to the Matsuda index. The diabetic cohort was divided into DMC and non-DMC groups. Fasting UCPCR (0hUCPCR) and 2-h post-OGTT/steamed bread meal (2hUCPCR) were measured. Multiple regression analysis was used to describe the association between UCPCR and the Matsuda index or DMC. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis.

In the non-diabetic individuals, both 0hUCPCR and 2hUCPCR were higher in the IR group, and they were negatively associated with the Matsuda index (r = −0.488, r = −0.636) (all P < 0.001) by Spearman’s correlation analysis. Multiple linear regression analysis demonstrated that 0hUCPCR (B = −0.351) and 2hUCPCR (B = −0.162) were negatively associated with the Matsuda index (all P < 0.001). ROC analysis revealed that the areas under the curve (AUC) for screening IR were 0.780 and 0.831, with corresponding sensitivities of 64.4% and 77.6%, respectively. In the T2DM patients, 0hUCPCR and 2hUCPCR were lower in the DMC group, and they showed positive correlations with HOMA-β (r = 0.582, r = 0.617) (all P < 0.001). Multivariable logistic regression analysis demonstrated that 2hUCPCR was negatively associated with DMC (OR = 0.627, P = 0.030). ROC analysis revealed that 2hUCPCR predicted DMC risk with an AUC of 0.751 and a sensitivity of 70.7%.

Both 0hUCPCR and 2hUCPCR are promising markers for IR in non-diabetic adults, and 2hUCPCR is associated with lower risk of DMC in T2DM patients. Coupled with their practical advantages of simplicity and non-invasiveness, UCPCRs are promising tools for future large-scale screening in at-risk populations.

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