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Potential metabolic biomarkers of critical limb ischemia in people with type 2 diabetes mellitus

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Abstract

Introduction

Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation.

Objective

To identify biomarkers for improving the screening of CLI in high-risk people with T2DM.

Methods

We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (1H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1H NMR data.

Results

Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values.

Conclusion

The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed.

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Data Availability

Not applicable.

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Funding

This work was supported by the Iran University of Medical Sciences, Tehran, Iran (Grant Number 12323).

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Authors and Affiliations

  1. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran

    Nahid Safari-Alighiarloo, Nahid Hashemi Madani & Mohammad E. Khamseh

  2. Chemometrics and Cheminformatics Laboratory, Department of Chemistry, Tarbiat Modares University, Tehran, Iran

    Ahmad Mani-Varnosfaderani

  3. Medical Informatics Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyyed Mohammad Tabatabaei

  4. Department of Interventional Radiology, Firouzgar Hospital, Iran University of Medical Science, Tehran, Iran

    Mohammad Reza Babaei

  5. Endocrine and Metabolism Research Institute, Firoozeh Alley, Valiasr Square, Tehran, Iran

    Nahid Safari-Alighiarloo

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  1. Nahid Safari-Alighiarloo
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  2. Ahmad Mani-Varnosfaderani
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  3. Nahid Hashemi Madani
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Contributions

NSA, NHM, and MEK conceived and designed the research. NHM, MRB, and SMT conducted experiments. AMV and NSA analyzed data and interpreted results. AMV and NSA wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Nahid Safari-Alighiarloo or Ahmad Mani-Varnosfaderani.

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The authors declare that there are no conflicts of interest.

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This study was in accordance with the Declaration of Helsinki 1964, and the study protocol was approved by the local ethics committee (IR.IUMS.REC.1397.738) at Iran University of Medical Sciences, Tehran, Iran.

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Safari-Alighiarloo, N., Mani-Varnosfaderani, A., Madani, N.H. et al. Potential metabolic biomarkers of critical limb ischemia in people with type 2 diabetes mellitus. Metabolomics 19, 66 (2023). https://doi.org/10.1007/s11306-023-02029-3

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