Metabolic insights into bariatric surgical diabetes resolution
File(s)
Author(s)
Yeung, Kai Tai Derek
Type
Thesis
Abstract
Background:
Bariatric surgery is currently the most effective form of treatment for individuals with severe obesity and Type 2 Diabetes (T2D) and induces systems-wide metabolic changes. While
effective, there is significant heterogeneity in the duration of T2D remission reported within the literature. The underlying mechanisms which contribute to improved glycaemic control
after surgery have not yet been completely elucidated. Therefore, there is currently no effective or reliable method of predicting the probability of surgical resolution of T2D in
the pre-operative setting. The constant evolution and technological improvements in the field of metabolomics have enabled scientists to explore systems biology with a different
perspective and investigating metabolic mechanisms that contribute to the resolution of T2D after surgery provides an opportunity to investigate this pathology with a different viewpoint.
Methods:
This thesis utilises predominantly Liquid Chromatography- Mass Spectrometry (LC-MS) as a metabolic profiling method. After pre-processing of the data, a combination of multivariate modelling, univariate statistics and correlation analysis was used as a method of exploratory analysis to explore the metabolic differences in a cohort of individuals with obesity and T2D...
Results
Amino acid (AA) and lipid signatures differentiating individuals with and without T2D were identified. Some of these metabolites were significantly correlated with glycated 7 haemoglobin (HbA1c). Bariatric surgery in particularly Roux-En-Y Gastric bypass resulted in a reduction in some of the metabolites linked to glycaemic control...
Conclusion:
The exploratory and discovery nature of this thesis has confirmed existing and identified several novel amino acid and lipid signatures linked to metabolic dysfunction in T2D and its association with T2D surgical resolution...
Bariatric surgery is currently the most effective form of treatment for individuals with severe obesity and Type 2 Diabetes (T2D) and induces systems-wide metabolic changes. While
effective, there is significant heterogeneity in the duration of T2D remission reported within the literature. The underlying mechanisms which contribute to improved glycaemic control
after surgery have not yet been completely elucidated. Therefore, there is currently no effective or reliable method of predicting the probability of surgical resolution of T2D in
the pre-operative setting. The constant evolution and technological improvements in the field of metabolomics have enabled scientists to explore systems biology with a different
perspective and investigating metabolic mechanisms that contribute to the resolution of T2D after surgery provides an opportunity to investigate this pathology with a different viewpoint.
Methods:
This thesis utilises predominantly Liquid Chromatography- Mass Spectrometry (LC-MS) as a metabolic profiling method. After pre-processing of the data, a combination of multivariate modelling, univariate statistics and correlation analysis was used as a method of exploratory analysis to explore the metabolic differences in a cohort of individuals with obesity and T2D...
Results
Amino acid (AA) and lipid signatures differentiating individuals with and without T2D were identified. Some of these metabolites were significantly correlated with glycated 7 haemoglobin (HbA1c). Bariatric surgery in particularly Roux-En-Y Gastric bypass resulted in a reduction in some of the metabolites linked to glycaemic control...
Conclusion:
The exploratory and discovery nature of this thesis has confirmed existing and identified several novel amino acid and lipid signatures linked to metabolic dysfunction in T2D and its association with T2D surgical resolution...
Version
Open Access
Date Issued
2022-08-12
Date Awarded
01/03/2023
License URL
Advisor
Holmes, Elaine
Darzi, Ara
Purkayastha, Sanjay
Penney, Nicholas
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)