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

Lin, Huan-Tang; Cheng, Mei-Ling; Lo, Chi-Jen; Lin, Gigin; Lin, Shu-Fu; Yeh, Jiun-Ting; Ho, Hung-Yao; Lin, Jr-Rung; Liu, Fu-Chao

doi:10.3390/jcm8060874

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

^1,2,3,†

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¹² and

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Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

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Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan

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Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

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Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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Department of Medical Imaging and Intervention, Imaging Core Lab, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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Division of Trauma, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan

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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

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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)

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Abstract

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

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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. https://doi.org/10.3390/jcm8060874

AMA 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. Journal of Clinical Medicine. 2019; 8(6):874. https://doi.org/10.3390/jcm8060874

Chicago/Turabian Style

Lin, Huan-Tang, Mei-Ling Cheng, Chi-Jen Lo, Gigin Lin, Shu-Fu Lin, Jiun-Ting Yeh, Hung-Yao Ho, Jr-Rung Lin, and Fu-Chao Liu. 2019. "¹H Nuclear Magnetic Resonance (NMR)-Based Cerebrospinal Fluid and Plasma Metabolomic Analysis in Type 2 Diabetic Patients and Risk Prediction for Diabetic Microangiopathy" Journal of Clinical Medicine 8, no. 6: 874. https://doi.org/10.3390/jcm8060874

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

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