Association of Matrix Metalloproteinase-9 and Tissue Inhibitor Metalloproteinase-1 with Diabetic Nephropathy in Patients with Type Ⅱ Diabetes Mellitus
Keywords:
Diabetes mellitus, Diabetic Nephropathy, Type II, Matrix Metalloproteinase-9, Tissue Inhibitor Metalloproteinase-1.Abstract
Background: Type 2 diabetes mellitus (T2DM) is one of the leading causes of chronic kidney disease (CKD) and end-stage renal failure worldwide. Among the factors implicated in the pathogenesis of diabetic nephropathy (DN). Dysregulation of the matrix metalloproteinases (MMPs) / tissue inhibitors of metalloproteinases (TIMPs) balance may serve as an early marker and a potential therapeutic target in DN.
Aim of the Study: To evaluate the association between serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and the progression of diabetic nephropathy in patients with T2DM.
Subjects and Methods: A case-control study was conducted at Baghdad Medical City between February and June 2025. Albumin-to-creatinine ratio (ACR) was measured in spot urine samples, the study included three groups of diabetic patients with 65 patients in each, namely the normoalbuminuria group, Microalbuminuria group and Macroalbuminuria group in addition to 65 healthy controls matched for age and sex were enrolled.
Results: The mean±SD age of participants was 55.96 ± 13.26 years, with a nearly equal male-to-female distribution. A significant higher levels of HbA1c, serum creatinine, MMP-9, and TIMP-1 reported in diabetic patients’ groups compared to controls (P<0.001). The mean MMP-1 was the lowest in controls , (47.12 ± 4.49 ng/mL) and the highest (97.01 ± 8.19 ng/mL) in the Macroalbuminuria group. Similar trend was found with regards to TIMP-1, (P<0.001). Both MMP-9 and TIMP-1 showed significant positive correlations with HbA1c (r = 0.62 and 0.61), serum creatinine (r = 0.56 and 0.55), and with each other (r = 0.86; p < 0.001). ROC analysis demonstrated high diagnostic performance of both biomarkers for predicting macroalbuminuria, with a (sensitivity of 92.3%, specificity 89.7%) for MMP-9 and (sensitivity of 93.8%, specificity 87.2%) for TIMP-1.
Conclusion: Elevated serum levels of MMP-9 and TIMP-1 was associated with the severity of diabetic nephropathy in patients with T2DM. The parallel increase in both markers with worsening albuminuria and renal dysfunction suggests that dysregulation of Extracellular Matrix remodeling contributes to Diabetic Nephropathy progression.
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