Approximately 90% of people undergoing bariatric surgery have NAFLD, which is a condition where fat accumulates in the liver and can lead to inflammation and scarring. It mostly causes no symptoms, however, in the most advanced cases there is an increased risk of liver cancer or liver failure. NAFLD is currently managed by weight loss and treating associated diseases such as diabetes. No medicines have been licensed to directly treat it but bariatric surgery has been shown to be usually beneficial, although it is unknown whether some operations are better than others. It is also unclear whether this is due to general weight loss or other factors. This study will be conducted in a hospital setting and aims to determine what changes in liver fat and fat processing occur after pre-operative low calorie diet and the two most common types of bariatric surgery (Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Participants will have ten study visits, four of which may be combined with NHS appointments. Participants will undergo investigations including MRI scans to measure changes in NAFLD and DEXA scans to measure changes in fat and fat-free mass (FFM). Participants will also undergo mixed meal testing to which stable isotopes (deuterated water and 13c-palmitate) will be added to allow changes in fat processing to be detected. In addition to samples taken as part of NHS care, blood, urine, liver and fat (visceral and subcutaneous (abdominal and gluteal)) will be used for research. Visits will take place before and after low calorie diet and bariatric surgery.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
RYGB operation using surgeons' standard technique
SG surgery using surgeons' standard technique
University of Oxford
Oxford, United Kingdom
Change in liver fat content
Change in liver fat content as measured on MRI scan +/- fibroscan
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Hepatic fatty acid synthesis
measured by incorporation of 2H2 palmitate from 2H2O into very low density lipoprotein triglyceride (VLDL-TG) and contribution of de novo lipogenesis and uptake and re-esterification to the hepatic triglyceride pool in liver biopsy
Time frame: liver biopsy taken during SG or RYGB
Changes in relative contributions of pathways involved in lipid homeostasis
measured using mathematical modelling of results from stable isotope mixed meal test
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Changes in fasting and postprandial plasma lipid concentration
measured using a clinical analyser (in fasting states and in response to mixed meal test)
Time frame: Baseline measurements just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Changes in fasting and postprandial plasma glucose concentration
measured using a clinical analyser measured using a clinical analyser (in fasting state and in response to mixed meal test)
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Change in the incorporation of 13C (from dietary fat) into CO2
measured using a breath analyser (in fasting state and in response to mixed meal test)
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Expression changes (gene/protein) in adipose tissue biopsies
measured using techniques such as quantitative real-time PCR (polymerase chain reaction) and ELISA (enzyme- linked immunosorbent assay)
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Change in fat mass
Proportional (% relative to baseline and lean mass) and absolute changes measured using DXA scan and bioimpedence analysis
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Change in lean mass
Proportional (% relative to baseline and fat mass) and absolute changes measured using DXA scan and bioimpedence analysis
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
Change in functional strength
measured using hand dynamometer
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
changes in fasting and post-prandial peptides/proteins (e.g. PYY, GLP-1, insulin)
measured using ELISA (in fasting state and in response to mixed meal test)
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
change in weight
measured in kilograms using weighing scales
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
change in body mass index (BMI)
weight measured in kilograms using weighing scales and combined with height in metres to report BMI in kg/m\^2
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
change in status of metabolic diseases (e.g. diabetes) / metabolic disease risk scores
measured with blood tests (e.g. hba1c), by recording clinical changes including medication requirements and clinical data (e.g. blood pressure)
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
complications, re-operation, mortality
clinical events will be recorded
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
changes in subcutaneous, visceral and pancreatic fat
measured on MRI scan
Time frame: Baseline measurement just prior to initiation of routine preoperative low calorie diet (this starts 3-4 weeks before surgery) compared to measurements on completion of this (within a week of surgery) and at 20% weight loss and 1 year after SG or RYGB
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