The Creatinine-to-Cystatin C (Cre/CysC) ratio has recently emerged as a composite biomarker integrating information on muscle mass, metabolic homeostasis, and renal hemodynamics. In type 2 diabetes mellitus (T2DM), subtle muscle decline, deteriorating glycemic control, and early renal alterations frequently coexist but remain challenging to detect using conventional indices. This study aimed to determine the median Cre/CysC ratio and examine its independent associations with glycemic control and renal injury markers in Vietnamese patients with T2DM.

A cross-sectional descriptive study was conducted on 124 T2DM outpatients at Military Hospital 175 from January 2025 to May 2025. Data collection included anthropometric parameters (BMI), fasting plasma glucose, HbA1c, plasma Creatinine, Cystatin C, and urinary Albumin-to-Creatinine Ratio (ACR). The estimated Glomerular Filtration Rate (eGFR) was calculated using the CKD-EPI 2021 equation (combining Creatinine and Cystatin C). Statistical analysis employed Pearson/Spearman correlation tests and multivariate linear regression to identify independent predictors.

The median Cre/CysC ratio was 11.8 (IQR: 11.1–12.8), with no statistically significant difference observed between males and females (p > 0.05). Analysis revealed a strong negative correlation between the Cre/CysC ratio and both BMI (r = -0.78; p < 0.05) and HbA1c (r = -0.5; p < 0.05). In multivariable analysis, Cre/CysC remained an independent negative predictor of HbA1c (β = –0.4; p < 0.05), indicating a robust association between lower ratios and poorer long-term glycemic control. A strong positive correlation was observed between Cre/CysC and ACR (r = 0.8; p < 0.05). Multivariable regression confirmed Cre/CysC (β = 0.4; p < 0.05) and diastolic blood pressure as independent predictors of ACR. This profile is consistent with early diabetic kidney disease physiology, where glomerular hyperfiltration enhances cystatin C clearance while microalbuminuria begins to manifest, reflecting early hemodynamic stress before overt eGFR decline.

The Cre/CysC ratio serves as a valuable biomarker in clinical practice for patients with T2DM. This index not only reflects muscle mass status but is also independently and closely associated with long-term glycemic control. In the early stages of the disease, an elevated Cre/CysC ratio accompanied by increased ACR suggests glomerular hyperfiltration, serving as an early warning of hemodynamic alterations prior to overt decline in renal function.