Analysis of reactive aldehydes in urine and plasma of type-2 diabetes mellitus patients through liquid chromatography-mass spectrometry: Reactive aldehydes as potential markers of diabetic nephropathy

Carla Harkin, Diego Cobice, Joanne Watt, Mary Jo Kurth, Simon Brockbank, Stephanie Bolton, Anna Strzelecka, John V Lamont, Tara C. B. Moore, Peter Fitzgerald, Mark Ruddock

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Abstract

Introduction: Diabetes is a major public health issue that is approaching epidemic proportions globally. Diabetes mortality is increasing in all ethnic groups, irrespective of socio-economic class. Obesity is often seen as the main contributor to an increasing prevalence of diabetes. Oxidative stress has been shown to trigger obesity by stimulating the deposition of white adipose tissue. In this study, we measured reactive aldehydes by liquid chromatography-mass spectrometry (LC-MS), in the urine and plasma of type-2 diabetic mellitus (T2DM) patients, as potential surrogates of oxidative stress. Our hypothesis was that reactive aldehydes play a significant role in the pathophysiology of diabetes, and these reactive species, may present potential drug targets for patient treatment.

Materials and methods: Study participants [N = 86; control n = 26; T2DM n = 32, and diabetic nephropathy (DN) n = 28] were recruited between 2019 and 2020. Urine and blood samples were collected from all participants, including a detailed clinical history, to include patient behaviours, medications, and co-morbidities. Reactive aldehyde concentrations in urine and plasma were measured using pre-column derivatisation and LC-MS, for control, T2DM and DN patients.

Results: Reactive aldehydes were measured in the urine and plasma of control subjects and patients with T2DM and DN. In all cases, the reactive aldehydes under investigation; 4-HNE, 4-ONE, 4-HHE, pentanal, methylglyoxal, and glyoxal, were significantly elevated in the urine and serum of the patients with T2DM and DN, compared to controls (p < 0.001) (Kruskal–Wallis). Urine and serum reactive aldehydes were significantly correlated (≥0.7) (p < 0.001) (Spearman rho). The concentrations of the reactive aldehydes were significantly higher in plasma samples, when compared to urine, suggesting that plasma is the optimal matrix for screening T2DM and DN patients for oxidative stress.

Conclusion: Reactive aldehydes are elevated in the urine and plasma of T2DM and DN patients. Reactive aldehydes have been implicated in the pathobiology of T2DM. Therefore, if reactive aldehydes are surrogates of oxidative stress, these reactive aldehyde species could be therapeutic targets for potential drug development.
Original languageEnglish
Article number997015
Pages (from-to)1-12
Number of pages12
JournalFrontiers in nutrition
Volume9
DOIs
Publication statusPublished (in print/issue) - 16 Jan 2023

Bibliographical note

Funding Information:
JW, MK, SiB, JL, and MR were paid employed by Randox Laboratories Ltd., but hold no shares in the company. PF was the Managing Director and owner of Randox Laboratories Ltd., a privately owned company. The authors declare that this study received funding from Randox Laboratories Ltd. The funder had the following involvement in the study: analysis of patient samples, statistical analysis, supervision of the project, preparation of the manuscript, and the decision to publish.

Funding Information:
This study was funded by the Randox Laboratories Ltd., Ulster University Ph.D. Academy.

Publisher Copyright:
Copyright © 2023 Harkin, Cobice, Watt, Kurth, Brockbank, Bolton, Johnston, Strzelecka, Lamont, Moore, Fitzgerald and Ruddock.

Keywords

  • type-2 diabetes
  • diabetic nephropathy
  • 4-hydroxynonenal (4-HNE)
  • 4-oxo-2-nonenal (4-ONE)
  • 4-hydroxyhexenal (4-HHE)
  • pentanal
  • methylglyoxal
  • glyoxal

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