Understanding the long-term impact of bariatric surgery on obesity-related complications and mortality

Supervisor: Dr Francesco Zaccardi  fz43@leicester.ac.uk

Project Description:

Bariatric surgery (BS) is a very effective treatment for severe obesity which improves obesity-related complications and survival [especially in people with type 2 diabetes, (T2D)] compared to non-operated obese population. However, in Nordic populations, the all-cause mortality after BS remains higher compared to the general population and is increased over time after BS. Weight regain (WR) after BS and recurrence of obesity-related complications may be the underlying cause for the increased mortality over time and indeed US data demonstrates that clinically significant WR is common after BS. Currently, limited data is available from the UK on the long-term mortality after BS, the long-term WR after BS and its impact on metabolic and cardiovascular complications. 

Aims and objectives: 

1. Assess whether the all-cause mortality and the mortality from cardiovascular disease, diabetes, cancer and suicide after BS are increased over time compared to the general UK population and obese population. 

2. Identify the best time for BS during the T2D continuum.

3. Describe the long-term WR after each BS type in the UK and investigate the association between WR post-BS and progression of metabolic and cardiovascular complications.

Methods: 
The PhD student will handle large electronic health records (CPRD linked to hospitalisation [HES] and mortality [ONS] data) under the supervision of the Leicester RWEU. Using advanced methods for data manipulation, the student will learn to construct an epidemiological cohort from secondary data to answer clinical questions. The analyses will be then conducted in the following 3 work packages, corresponding to the objectives: 

Workpackage-1 analysis: Individuals who have had BS procedures will be compared to matched individuals without BS to measure the rates of cause-specific deaths. Factors associated with a higher risk will also be explored, including whether the differential risk has changed over the last decades.

Workpackage-2 analysis: In individuals with T2D, the rates of diabetes complications and mortality following BS will be compared across varying disease duration. 
Workpackage-3 analysis:  The longitudinal trajectories (and their determinants) of the body weight after BS will be explored. The longitudinal changes will be then related to the outcomes using advanced statistical modelling (joint longitudinal-survival models).

References:
[1] Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. Lancet. 2021; 397(10287):1830-1841.
[2] Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study. Gastroenterology. 2019; 157(1):119-127.
[3] Comparison of the Performance of Common Measures of Weight Regain After Bariatric Surgery for Association With Clinical Outcomes. JAMA. 2018; 320:1560-1569.