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Open AccessArticle

1H Nuclear Magnetic Resonance (NMR)-Based Cerebrospinal Fluid and Plasma Metabolomic Analysis in Type 2 Diabetic Patients and Risk Prediction for Diabetic Microangiopathy

by Huan-Tang Lin 1,2,3,†, Mei-Ling Cheng 4,5,6,†, Chi-Jen Lo 4, Gigin Lin 6,7, Shu-Fu Lin 8, Jiun-Ting Yeh 9, Hung-Yao Ho 10,11, Jr-Rung Lin 12 and Fu-Chao Liu 1,2,*
1
Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
2
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
3
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
4
Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
5
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
6
Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
7
Department of Medical Imaging and Intervention, Imaging Core Lab, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
8
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
9
Division of Trauma, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
10
Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
11
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
12
Clinical Informatics and Medical Statistics Research Center and Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(6), 874; https://doi.org/10.3390/jcm8060874
Received: 8 May 2019 / Revised: 15 June 2019 / Accepted: 16 June 2019 / Published: 19 June 2019
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
Insulin resistance and metabolic derangement are present in patients with type 2 diabetes mellitus (T2DM). However, the metabolomic signature of T2DM in cerebrospinal fluid (CSF) has not been investigated thus far. In this prospective metabolomic study, fasting CSF and plasma samples from 40 T2DM patients to 36 control subjects undergoing elective surgery with spinal anesthesia were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy. NMR spectra of CSF and plasma metabolites were analyzed and correlated with the presence of T2DM and diabetic microangiopathy (retinopathy, nephropathy, and neuropathy) using an area under the curve (AUC) estimation. CSF metabolomic profiles in T2DM patients vs. controls revealed significantly increased levels of alanine, leucine, valine, tyrosine, lactate, pyruvate, and decreased levels of histidine. In addition, a combination of alanine, histidine, leucine, pyruvate, tyrosine, and valine in CSF showed a superior correlation with the presence of T2DM (AUC:0.951), diabetic retinopathy (AUC:0.858), nephropathy (AUC:0.811), and neuropathy (AUC:0.691). Similar correlations also appeared in plasma profiling. These metabolic alterations in CSF suggest decreasing aerobic metabolism and increasing anaerobic glycolysis in cerebral circulation of patients with T2DM. In conclusion, our results provide clues for the metabolic derangements in diabetic central neuropathy among T2DM patients; however, their clinical significance requires further exploration. View Full-Text
Keywords: type 2 diabetes; microangiopathy; cerebrospinal fluid; metabolomics; nuclear magnetic resonance type 2 diabetes; microangiopathy; cerebrospinal fluid; metabolomics; nuclear magnetic resonance
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MDPI and ACS Style

Lin, H.-T.; Cheng, M.-L.; Lo, C.-J.; Lin, G.; Lin, S.-F.; Yeh, J.-T.; Ho, H.-Y.; Lin, J.-R.; Liu, F.-C. 1H Nuclear Magnetic Resonance (NMR)-Based Cerebrospinal Fluid and Plasma Metabolomic Analysis in Type 2 Diabetic Patients and Risk Prediction for Diabetic Microangiopathy. J. Clin. Med. 2019, 8, 874.

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