1887
Volume 2025, Issue 1
  • EISSN: 2220-2749

Abstract

Diabetic nephropathy (DN) represents one of the most severe complications associated with type 2 diabetes (T2D), often leading to kidney failure and significantly affecting patients’ quality of life. Early detection and monitoring of DN are essential to prevent its progression. Midkine and copeptin, two biomarkers associated with inflammatory and metabolic processes, have shown promise in reflecting the underlying changes associated with DN, thus offering hope for improved diagnosis and management. The objective of this study was to investigate the clinical relevance of midkine and copeptin levels in T2D patients and their associations with insulin resistance and albuminuria status, evaluating their potential as predictive tools to detect the progression of DN.

A case–control study was carried out with 360 participants, grouped into 90 healthy controls and T2D patients categorized by different stages of albuminuria (normoalbuminuric, microalbuminuric, and macroalbuminuric, with 90 individuals in each category). Serum levels of midkine, copeptin, fasting insulin, and other biochemical analytes were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), while renal function was evaluated using the albumin–creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR).

Elevated levels of midkine and copeptin were found in T2D patients, with the highest levels observed in the macroalbuminuric group ( < 0.001). Both biomarkers were positively correlated with glycemic parameters (fasting glucose, HbA1c), insulin resistance (HOMA-IR), and markers of DN (ACR, eGFR) ( < 0.001). ROC (receiver operating characteristic) analysis showed strong diagnostic performance for both biomarkers, with midkine yielding an area under the curve (AUC) of 0.96 (95% CI: 0.94–0.99, sensitivity: 96.7%, specificity: 91.1%) and copeptin yielding an AUC of 0.98 (95% CI: 0.97–1.0, sensitivity: 97.8%, specificity: 88.9%). Multivariate linear regression analysis identified midkine ( = 0.039) and copeptin ( = 0.027) as significant predictors of albuminuria.

Serum levels of midkine and copeptin are elevated in T2D patients, with a strong association with the onset and progression of DN. These biomarkers may serve as early indicators for diabetic kidney disease, facilitating timely detection and management of renal complications. Their role in predicting insulin resistance and cardiovascular risk further underscores their potential as clinical tools for managing DN.

© 2025 The Author(s), licensee HBKU Press.
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2025-06-04
2025-12-07

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Serum midkine and copeptin as predictive biomarkers for diabetic nephropathy progression in type 2 diabetes mellitus
Avicenna 2025, 7 (2025); https://doi.org/10.5339/avi.2025.7
/content/journals/10.5339/avi.2025.7
/content/journals/10.5339/avi.2025.7
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  • Article Type: Research Article
Keyword(s): albuminuria, copeptin, Diabetic nephropathy, insulin resistance and midkine

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