Abstract Disclosure: L. Leyva Figueroa: None. F.J. Gomez-Perez: None. F. Gonzalez-Valdivia: None. D. Cuevas-Ramos: None. Background: High C-peptide levels have been associated with microvascular complications, although there is controversial evidence in patients with T2DM. Objective: To correlate fasting serum C-peptide values in patients with T2DM with diabetic nephropathy. Hypothesis: In patients with type 2 diabetes mellitus there is a positive correlation of minimum r=0.3 between fasting C-peptide, albumin/creatinine ratio (ACR) and glomerular filtration rate (eGFR). Research Question: Is there a significant and independent correlation between fasting C-peptide values, ACR, and eGFR in patients with type 2 diabetes mellitus? Methods: Retrospective, cross-sectional, observational, real-world study, in 551 type 2 diabetic patients. Data was collected from the electronic clinical records. Microalbuminuria was defined as an ACR equal or greater than 30, and eGFR was calculated by CKD-EPI 2021. Fasting C-peptide was measured by immunochemiluminescence. Continuous variables were expressed as means +/− standard deviation, while categorical variables will be expressed as percentages. We used one-way ANOVA to compare continuous variables between groups, and Chi-square test to compare categorical variables. Multivariate logistic regression analysis was used to analyze the independent relationship between C-peptide quartiles, eGFR, and ACR, adjusted for weight, insulin, and disease duration. Results: 551 patients were evaluated (63% were women), with mean age of 62 ±11 years old, and a HbA1c of 8.4%. Median (interquartile range) of disease duration was 20 years (12-25), with a C-peptide median level of 1.6 (0.9-2.4 ng/ml), with no significant difference by gender. A statistically significant direct relationship was found between a higher C-peptide quartile and higher ACR (F=9.8, p= 0.03). A significant correlation was also found between C-peptide and ACR (r=0.16, p<0.001), and also with eGFR (r=−0.11, p=0.01). Using a multivariate regression analysis we identified an independent association between C-peptide and ACR (beta=44.7, CI95%, 16-73, p=0.002), and also with eGFR (beta −2.7, CI95% −4.7 to −0.6, p=0.01). Conclusions: A significant and independent association was found between C-peptide levels and kidney function and albuminuria. Future studies may confirm that C-peptide can stand as an early marker for diabetic nephropathy. Presentation: Friday, June 16, 2023