Metabolites (Jul 2023)

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

  • Lavinia Balint,
  • Carmen Socaciu,
  • Andreea Iulia Socaciu,
  • Adrian Vlad,
  • Florica Gadalean,
  • Flaviu Bob,
  • Oana Milas,
  • Octavian Marius Cretu,
  • Anca Suteanu-Simulescu,
  • Mihaela Glavan,
  • Silvia Ienciu,
  • Maria Mogos,
  • Dragos Catalin Jianu,
  • Sorin Ursoniu,
  • Victor Dumitrascu,
  • Daliborca Vlad,
  • Roxana Popescu,
  • Ligia Petrica

DOI
https://doi.org/10.3390/metabo13080893
Journal volume & issue
Vol. 13, no. 8
p. 893

Abstract

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Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood–brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction.

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