Clinical relevance of midkine as a biomarker predicting atherosclerotic risk factors in individuals with type-2 diabetes mellitus: a cross-sectional study

J Diabetes Metab Disord. 2024 Dec 20;24(1):20. doi: 10.1007/s40200-024-01547-8. eCollection 2025 Jun.

Authors

Isam Noori Salman¹, Noor Ulhuda G Mohammed², Alaa Shaban³, Baydaa Ahmed Abed¹, Samara Ali Mutar², Hussein Hatam Omran⁴

Affiliations

¹ National Diabetes Center, Mustansiriyah University, Baghdad, Iraq.
² Department of Chemistry, College of Science for Women, University of Baghdad, Baghdad, Iraq.
³ Department of Chemistry, College of Science, University of Babylon, Hilla, Iraq.
⁴ Iraqi Ministry of Health, Baghdad, Iraq.

PMID: 39712344
PMCID: PMC11659568 (available on 2025-12-20)
DOI: 10.1007/s40200-024-01547-8

Abstract

Objective: Midkine (MK) is a member of a small protein family that includes pleiotrophin. MK levels are elevated in obese patients and have a pro-arthrogenic effect through various pathophysiological processes including vascular inflammation and atherogenesis. This study aimed to investigate the association between serum MK levels and several atherosclerotic risk factors in patients with type 2 diabetes mellitus (T2DM).

Methodology: Ninety subjects were enrolled in this study, comprising 60 T2DM patients and 30 age-matched healthy subjects (HS). The patients were categorized into two groups based on dyslipidemia: group 1 consisted of 30 patients with dyslipidemia, while group 2 included 30 patients without dyslipidemia. Laboratory tests were conducted using routine assays at the National Diabetes Center. MK levels were analyzed using enzyme-linked immunosorbent assay (ELISA).

Results: MK levels were significantly higher in patients with dyslipidemia compared to those without dyslipidemia and HS (P ≤ 0.0001). A significant negative correlation was observed between MK levels and the atherogenic index of plasma (AIP), Castelli's risk index-1 (CRI-I), and Castelli's risk index-2 (CRI-II) (r = - 0.489, p = 0.005; r = - 0.465, p = 0.008; r = - 0.421, p = 0.018, respectively) in patients with dyslipidemia. Furthermore, a significant positive correlation was found between MK levels and HDL-C (r = 0.524, p = 0.002) in patients without dyslipidemia. MK, AIP, and CRI-I were identified as predictors of atherosclerosis in DM patients, with MK indicating very good discriminate power (AUC = 0.805) in identifying T2DM patients with dyslipidemia at a cut-off value of ≤ 4.457 ng/ml.

Conclusion: These findings suggest that MK could be considered a predictive biomarker for dyslipidemia associated with DM. MK levels correlate significantly with atherogenic risk factors, indicating its potential as a sensitive risk predictor for atherosclerosis in patients with T2DM.

Keywords: Atherosclerosis; Dyslipidemia; Lipid ratio; Midkine; T2DM.

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