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Study of Longitudinal Changes in Fasting Bile Acids After Sleeve Gastrectomy or Roux-en-Y Gastric Bypass Bariatric Surgeries in T2DM Patients, and Identification of Novel Biomarkers Related to Metabolism

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Thesis is embargoed till 20 September 2026(2.71 MB)

Date

2023

Authors

Supervisor

Leong, Joe Chang Wee
Lu, Jun

Item type

Thesis

Degree name

Master of Science

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Publisher

Auckland University of Technology

Abstract

Diabetes type 2 (caused by obesity) and its complications has gradually become one of the most severe threats to human health in recent years. Bariatric surgery has gradually become a popular treatment option for obese type 2 diabetics, as a result of its ability to effectively reduce patients' weight. This surgery also improves glucose metabolism and provides long-term stable relief from diabetes for patients. Several recent studies have found that bile acid metabolism can affect the development of factors associated with the metabolic syndrome, as well as act as an important signaling molecule. Several cross-sectional studies have shown that serum bile acids are significantly elevated prior to weight loss after bariatric surgery. Despite this, few studies have been conducted to determine whether serum bile acids remain elevated for a long period of time following bariatric surgery, and whether this influences blood glucose levels. While there have been many advances in the study of various biomarkers of type 2 diabetes such as fasting glucose, urine glucose, glycosylated hemoglobin, and glucose tolerance, current methods still have many limitations. It is therefore imperative to identify novel biomarkers, such as bile acids, which are closely related to the development and progression of diabetes, in order to develop a theoretical basis for more rational and effective clinical monitoring and surveillance of diabetes development. A total of 47 patients with obesity-induced type 2 diabetes were recruited and randomized to two different bariatric surgery groups: SG (Sleeve Gastrectomy) and RYGB (Roux-en-Y gastric bypass) surgery. Prior to surgery, clinical characteristics, lipid profile, body composition, and diabetes characteristics were monitored using bioelectrical impedance analysis, dual-energy X-ray absorption, open circuit indirect calorimeter, and auto-analyzer. LC-MS/MS (High-performance liquid chromatography with tandem mass spectrometry) was used to analyze fasting bile acids (BAs), and the same parameters were measured in a second cohort one and five years after surgery. The preoperative and postoperative data were then compared. In this study, all clinical parameters measured before surgery were not significantly different between the SG and RYGB groups. Both groups of patients showed significant weight loss, changes in body composition, lipid profiles, and glycated haemoglobin levels after surgery. There was a significant increase in bile acid levels at one year following surgeries compared to preoperative levels. The BAs fraction, except for UDCA, GCA and GUDCA, decreased significantly from baseline at 5 years after SG or RYGB surgery. A similar rebound was observed in weight, body composition, lipid profile, and glycated haemoglobin. In addition, the BAs conjugation levels at five years following surgeries remained similar to those of the preoperative period. Compared to baseline, glycine conjugated, taurine conjugated, conjugated, unconjugated, primary conjugated, secondary conjugated, and secondary unconjugated bile acid levels at five years after surgeries were significantly lower in both surgery groups. With the rapid development of imaging technology, it is possible to observe human molecular imaging markers non-invasively, in addition to the study of biochemical markers (bile acids). Using ELISA (Enzyme-linked immunosorbent assay) and Liquid chromatography-mass spectrometry (LC-MS/MS) techniques, we examined the hormone levels (including leptin, gastrin, ghrelin, irisin, and secretin) of seven additional obese type 2 diabetic patients before and 3 days after undergoing RYGB surgery. None exhibited significant changes. Only secondary unconjugated BAs were observed to be altered significantly over this period. Following surgery, there was a significant reduction in intra-pancreatic fat deposition as quantified by MRI (Magnetic Resonance Imaging). Therefore, non-invasive imaging techniques are able to accurately measure adipose tissue for the early detection of diabetes. The discovery of novel diabetes biomarkers will not only improve the diagnosis rate and monitoring of the onset of diabetes progression but will also contribute to a better understanding of the pathophysiological processes and molecular mechanisms of human-style diabetes, opening up new directions for drug development.

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http://hdl.handle.net/10292/16696

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