Variations in Plasma Dimethylarginine and Bile Acids in Obese Patients with Type 2 Diabetes and Major Depression

  • Colin Stone

Student thesis: Doctoral Thesis

Abstract

Diabetes mellitus is characterised by episodes of hyperglycaemia (abnormally raised blood glucose concentration), primarily caused by defects in insulin secretion or action. In type 2 diabetes mellitus, there is an inadequate secretion of insulin by the pancreas or defect in end organ insulin action.
Chronic episodes of hyperglycaemia can result in systemic macro- and microvascular damage to the endothelial lining of blood vessels, which contributes to the progression of cardiovascular disease and leads to premature death. Factors like major depression, obesity and sedentary lifestyle are known to exacerbate the progression of cardiovascular disease in type 2 diabetes mellitus individuals and alter bile acid synthesis and function.
Dimethylarginines (asymmetric and symmetric dimethylarginine) are modified forms of the amino acid arginine that are synthesised by post-translational modification of nuclear proteins in all cells during the process of protein turnover from the action of protein-arginine methyl transferases, then released during proteolysis. Studies have shown that asymmetric dimethylarginine inhibits nitric oxide production in the endothelial lining, resulting in the progression of cardiovascular disease in type 2 diabetics.
This study is to confirm the hypothesis that variations in dimethylarginine and bile acid concentrations in obese and non-obese type 2 diabetics show significance based on depression status using stored serum samples from the South London Diabetes study from using a novel mass spectrometry method.
The study showed a significant difference in asymmetric dimethylarginine, symmetric dimethylarginine and their corresponding arginine ratios in the obese phenotype, and significance for asymmetric dimethylarginine and its corresponding arginine ratio in the depressed thin phenotype cohorts (pBased on the statistical analysis and known study limitations, the hypothesis was rejected as there was not enough evidence to support the hypothesis statement from this study.
Date of Award30 Dec 2019
Original languageEnglish
Awarding Institution
  • University of Portsmouth
SupervisorKaren Ball (Supervisor)

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