Metabolomic Signature of Diabetic Kidney Disease in Cerebrospinal Fluid and Plasma of Patients with Type 2 Diabetes Using Liquid Chromatography-Mass Spectrometry

Abstract

Diabetic kidney disease (DKD) is the major cause of end stage renal disease in patients with type 2 diabetes mellitus (T2DM). The subtle metabolic changes in plasma and cerebrospinal fluid (CSF) might precede the development of DKD by years. In this longitudinal study, CSF and plasma samples were collected from 28 patients with T2DM and 25 controls, during spinal anesthesia for elective surgery in 2017. These samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) in 2017, and the results were correlated with current DKD in 2017, and the development of new-onset DKD, in 2021. Comparing patients with T2DM having new-onset DKD with those without DKD, revealed significantly increased CSF tryptophan and plasma uric acid levels, whereas phosphatidylcholine 36:4 was lower. The altered metabolites in the current DKD cases were uric acid and paraxanthine in the CSF and uric acid, L-acetylcarnitine, bilirubin, and phosphatidylethanolamine 38:4 in the plasma. These metabolic alterations suggest the defective mitochondrial fatty acid oxidation and purine and phospholipid metabolism in patients with DKD. A correlation analysis found CSF uric acid had an independent positive association with the urine albumin-to-creatinine ratio. In conclusion, these identified CSF and plasma biomarkers of DKD in diabetic patients, might be valuable for monitoring the DKD progression.

Inulin Reduces Kidney Damage in Type 2 Diabetic Mice by Decreasing Inflammation and Serum Metabolomics

“…Metabolomics analysis showed that the contents of various metabolites related to fatty acid metabolism and inflammatory response were abnormal in the plasma of T2DM mice. Studies have shown that the level of L-acetylcarnitine in diabetic patients was a specific diagnostic indicator of diabetic complications, and the large accumulation of L-acetylcarnitine in plasma may imply impaired mitochondrial function and fatty acid oxidation in diabetic patients [ 61 ]. L-Palmitoylcarnitine is a long-chain acylcarnitine, which is the product of fatty acid metabolism.…”

Metabolites Potentially Derived from Gut Microbiota Associated with Podocyte, Proximal Tubule, and Renal and Cerebrovascular Endothelial Damage in Early Diabetic Kidney Disease in T2DM Patients

“…Cerebral small vessel disease (CSVD) is a disorder characterized by endothelial dysfunction that may be detected via MRI or cerebral Doppler ultrasound. These methods either show cerebral lacunes, microinfarcts, microbleeds, and white matter hyperintensities, as is the case with MRI, or they reveal poor vasodilatation, through the use of complex neurosonological methods [ 30 ] Because these techniques of diagnosis fail to detect early endothelial damage, sorbitol determination may be useful in assessing BBB function and the CVR, thus serving as a future possible therapeutic target.…”

Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients

“…Koppe et al described the implication of p-cresyl sulfate in the processes of insulin resistance in patients with CKD [45]. Although several authors have described p-cresyl sulfate concentration in serum [46,47], few studies have been developed with regard to urinary concentrations of p-cresyl sulfate.…”