Assessment of Metabolic Profiles of Lower Extremity Arterial Disease in Patiens Withe Type 2 Diabetes

Study Overview
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Brief Summary
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The prevalence of lower extremity arterial disease (LEAD) in patients with diabetes increases significantly and are characterized with obvious arteriosclerosis that are caused by multiple metabolic disorders. Metabolomics measures the metabolites in biological fluids or tissues that generated under certain conditions via rapidly evolving high-throughput technology. Herein, the investigators designed the study to characterize the serum metabolic profiles of LEAD patients and identify metabolic biomarkers using metabolomics. The serum of volunteers, type 2 diabetes mellitus(T2DM) patients with or without LEAD were collected and analyzed using liquid chromatography-mass spectrometry(LC-MS) coupled with a series of multivariate statistical analyses.

Official Title
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Assessment of Metabolic Profiles of Lower Extremity Arterial Disease in Patiens Withe Type 2 Diabetes Via LC-MS-based Nontargeted Metabolomic Approach

Conditions
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Diabetic Angiopathies, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: liquid chromatography-mass spectrometry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ranges from 18 to 100 years old Signed informed consent and agreed to participate in this study The diagnosis of T2DM is based on standard criteria recommended by WHO since 1999 The diagnosis of T2DM patient with LEAD is based on standard criteria recommended by Chinese guideline on prevention and management of diabetic foot (2019 edition)(II). Exclusion Criteria: younger than 18 years old or older than 100 years old acute infection during the preceding 3 months drugs or alcohol addicts cancer type 1 diabetes patients with mental abnormality who are uncooperative with this study pregnant or lactating women refuse to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group1<br>Volunteers with normal glucose tolerance. | Other: liquid chromatography-mass spectrometry<br>* Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography-mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and repro- ducibility.<br>* Other names: Metabolomics;|
| Group2<br>type 2 diabetic patients without microvascular (retinopathy, nephropathy or neuropathy) or macrovascular (coronary, cerebrovascular or lower extremity arterial disease) complications. | Other: liquid chromatography-mass spectrometry<br>* Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography-mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and repro- ducibility.<br>* Other names: Metabolomics;|
| Group3<br>type 2 diabetic patients with lower extremity artery disease diagnosed through the measurement of ABI (the ratio of ankle-to-brachial systolic blood pressure). | Other: liquid chromatography-mass spectrometry<br>* Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography-mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and repro- ducibility.<br>* Other names: Metabolomics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic profiles of lower extremity artery disease | LC-MS analysis will be performed using a Q ExactiveTM HF-X liqiud chromatograph system coupled with a Thermo ScientificTM OrbitrapTM mass spectrometer according to a previously published procedure to detect the peak, identify the metabolites and perform the PCA and OPLS-DA analyses to better visualize the subtle similarities and differences among the complex datasets. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potential biomarker analysis for discrimination | Screening for potential biomarkers will be performed according to the VIP value (VIP > 1.0) and significance test (P < 0.05) from the OPLS-DA model. | 4 months | 
| Pathway analysis of differential metabolites | Conducting pathway analysis for the significant metabolites identified by using MetaboAnalyst. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Lower extremity artery disease, Metabolic Profiles, Metabolic biomarkers, Metabolomics, iquid chromatography-mass spectrometry