Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Bariatric surgery is one of the most efficient ways in reducing the incidence of type 2 diabetes (T2D) and related mortality in obese individuals compared with the conventional intensive medical treatment. It rapidly improves insulin sensitivity/secretion and glycemic control which, intriguingly, is independent of weight loss. Possible factors responsible for the improvement include increased production of incretins in the post-operative intestine, altered levels of circulating bile acids, branch-chain amino acids (BCAAs) and short chain fatty acids (SCFAs), and modified gut microbiota.
Although bariatric surgery is currently recommended as a treatment option for T2D by the International Diabetes Federation and American Diabetes Association, only a very small percentage of T2D patients is currently using this therapeutic option. This is partly due to its highly invasive nature, and more importantly, owing to the fact that the remission rate is only 74.2% after 1 year, and further dropped to 57.6% after 3 years in Chinese population. Furthermore, the recurrence of T2D in some patients has also been reported in long-term studies. There is currently no reliable predictive and prognostic biomarker(s) for the clinical outcome of bariatric surgery.
The overall goal of the study is to identify sensitive biomarker(s) that is predictive for the metabolic outcomes of bariatric surgery in obese Chinese with T2D and to unveil the molecular basis underlying the adiposity-independent benefits on T2D. To achieve this, two prospective study cohorts in Chinese have been employed, including one 5-year follow-up bariatric surgery cohort consisting of 120 obese patients with T2D, and another prospective biobank of obese individuals with or without T2D undergone bariatric surgery. The serum/urine samples, together with subcutaneous and visceral adipose tissue biopsies from these two cohorts, at both baseline and year-5, will be used for proteomics/metabolomics analysis to search for novel predictive biomarkers or metabolites for the remission of T2D. The findings will be replicated and cross-validated in a bariatric surgery cohort recruited in Germany. Following that, the molecular mechanisms whereby these markers contribute to pathogenesis of T2D will be examined using animal and cell-based studies. The implementation of the study will characterise new strategies to predict the prognosis of bariatric surgery and its molecular basis, and provide new insight to development of novel therapies that mimic metabolic benefits of bariatric surgery.
Professor A Xu, Department of Medicine
Professor Aimin Xu has been focusing on both basic and translational research on obesity/diabetes-related disorders. He is leading the State Key Laboratory of Pharmaceutical Biotechnology, which is at the forefront of innovation and discovery in the field of molecular metabolism, with a focus on hormones and biomarkers. Professor Xu has made significant contributions to discovery and functional characterisation of several adipokines and hormones including adiponectin, fibroblast growth factor 21 (FGF21), adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2.
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