Chaiyasoot, Kusuma;
(2021)
Identifying factors associated with metabolic and weight-loss success following bariatric surgery.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Background/Objectives: Bariatric surgery is the most effective treatment for people with severe obesity. In order to maximise the benefit to risk ratio and gain more insights into the pathophysiology of obesity, identifying factors associated with metabolic and weight- loss success after bariatric surgery would be valuable. Methods: Three studies were performed. 1) Association study of pre- and early post- operative (6 weeks) factors with 1-year weight loss after LRYGB and LSG were examined in a prospective cohort of 85 subjects. 2) 13 subjects with T2D remission were compared with matched percentage weight loss (PWL) 13 subjects without remission. Gut hormones, hepatic, pancreatic and visceral fat, insulin sensitivity, beta-cell function and metabolomics were compared between groups. 3) 1,401 patients with severe obesity who were due to undergo primary bariatric surgery were prospectively investigated and genotyped. The GWAS was performed to identify SNPs associated with PWL after surgery. Two genetic risk scores (GRSs) of 941 variants associated with BMI and 49 variants associated with WHR adjusted for BMI (WHRadjBMI) were also constructed to examine the association with PWL. Results: 6-week post-operative PWL, weight change velocity, and PYY parameters were significantly associated with 52-week PWL. The rise in an AUC of postprandial PYY at 6 weeks from pre-surgery less than 16,000 pg x min/mL was connected with 8 times greater chance of being poor weight loss (PWL<20%) at 1 year. T2D remitters had significantly greater beta-cell function, circulating levels of FGF-19 and acyl ghrelin, but lower visceral fat area and plasma branched-chain amino acids (BCAAs) levels than non-remitters. The GWAS revealed 4 significant SNPs (KLF3-rs1491199, MAMDC2-rs2975907, GSAP- rs740158, CASZ1-rs7555879) associated with 52-week PWL. There is a significantly negative association between GRS of WHRadjBMI and PWL at 2 and 3 years. Conclusions: Genetics and 6-week weight loss and PYY parameters could predict the weight loss outcome from bariatric surgery. b-cell function, acyl ghrelin, FGF-19, visceral fat and BCAAs related to T2D remission.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Identifying factors associated with metabolic and weight-loss success following bariatric surgery |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10139250 |
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