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.
Highlights
Type 2 diabetes mellitus (T2DM) makes up 90–95% of all diabetes and is characterized by chronic hyperglycemia due to impaired target tissue response to insulin and progressive deterioration of pancreatic β-cell function [1]
The type 2 diabetes mellitus (T2DM) patients were further divided into subgroups of different microangiopathies according to recent medical records based on the following definitions: (1) Diabetic retinopathy defined by the presence of non-proliferative diabetic retinopathy or proliferative diabetic retinopathy in retinal photography, and the diagnosis verified by ophthalmologists
The T2DM patients were significantly higher in age, male percentage, height, weight, and body mass index (BMI) compared to the control group
Summary
Type 2 diabetes mellitus (T2DM) makes up 90–95% of all diabetes and is characterized by chronic hyperglycemia due to impaired target tissue response to insulin (i.e., insulin resistance) and progressive deterioration of pancreatic β-cell function [1]. Diabetes affected more than 425 million people worldwide in 2017, which is 281% higher than that published in the Diabetes Atlas in 2000, and diabetes accounts for 9.9% of all-cause adult mortality worldwide [2]. This global pandemic of T2DM most likely correlates with a sedentary lifestyle, western diet, overconsumption of high-calorie foods, and other risk factors of metabolic syndrome. The chronic hyperglycemia status in diabetic patients is associated with significant long-term sequelae, ranging from macrovascular (coronary artery disease, peripheral artery disease, atherosclerosis, and stroke) to microvascular complications (retinopathy, nephropathy, and neuropathy) [3]. Chronic hyperglycemia leads to downstream diabetic complications through activation of reactive oxygen species (ROS), the generation of advanced glycation end products (AGEs), the flux of the polyol pathway, activation of protein kinase C, excess release of inflammatory cytokines, and exaggerated oxidative stress [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
