Insulin resistance and metabolic derangement are present in patients with type 2 diabetes\nmellitus (T2DM). However, the metabolomic signature of T2DM in cerebrospinal fluid (CSF) has\nnot been investigated thus far. In this prospective metabolomic study, fasting CSF and plasma\nsamples from 40 T2DM patients to 36 control subjects undergoing elective surgery with spinal\nanesthesia were analyzed by 1^H nuclear magnetic resonance (NMR) spectroscopy. NMR spectra\nof CSF and plasma metabolites were analyzed and correlated with the presence of T2DM and\ndiabetic microangiopathy (retinopathy, nephropathy, and neuropathy) using an area under the curve\n(AUC) estimation. CSF metabolomic profiles in T2DM patients vs. controls revealed significantly\nincreased levels of alanine, leucine, valine, tyrosine, lactate, pyruvate, and decreased levels of histidine.\nIn addition, a combination of alanine, histidine, leucine, pyruvate, tyrosine, and valine in CSF showed\na superior correlation with the presence of T2DM (AUC:0.951), diabetic retinopathy (AUC:0.858),\nnephropathy (AUC:0.811), and neuropathy (AUC:0.691). Similar correlations also appeared in plasma\nprofiling. These metabolic alterations in CSF suggest decreasing aerobic metabolism and increasing\nanaerobic glycolysis in cerebral circulation of patients with T2DM. In conclusion, our results provide\nclues for the metabolic derangements in diabetic central neuropathy among T2DM patients; however,\ntheir clinical significance requires further exploration.
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