Obesity, is a determinant of health and a leading cause of diseases and premature death globally. Overweight and obesity, defined as abnormal or excessive fat accumulation that presents a risk to health, have been shown to increase the risk of heart attacks, high blood glucose levels (Type 2 diabetes), certain cancers and death. Complication development may occur more frequently and sooner in those with obesity. The type of complications (e.g., heart disease) may vary as well. At the same time, a risk factor common in people with obesity, e.g., high blood pressure, may also play a different role in the development of diseases or death. There may be differences in outcomes and obesity related-complications by sociodemographic characteristics. For example, it has been reported that there are marked ethnic differences in the development of diseases in relation to obesity, suggesting BMI as an important determinant of health inequality within minority groups. Prevalence of obesity is also higher in those who are more deprived. Using CPRD data, this study aims to explore the trajectories of risk factors, complications and mortality in individuals with obesity, compared to non-obese patients; and to explore how the diseases of the vessels and cancer vary by age, sex, ethnicity, and deprivation, and in relation to intervention to reduce body weight, such as bariatric surgery or medications. These analyses will add to the body of knowledge on obesity and related interventions, thereby improving patient care either directly or indirectly by informing clinical practice guidelines and/or public health policy.
There is limited evidence detailing the natural history of obesity sequelae from diagnosis as measured by body mass index (BMI), and how this history is influenced by the characteristics of patients or by medical or surgical interventions. To explore the intersectionality in obesity trajectories, complications and mortality by age, sex, ethnicity, and deprivation, using CPRD Aurum data linked to hospital admissions and death registry data, we will conduct a cohort study of patients aged 16 and over with a recorded BMI between January 2000 and June 2024. We will also develop two matched sub-cohorts for patients who had bariatric surgery, and obesity medications, matched to those who did not. We will investigate the development of a single and multiple diseases in individuals across levels of BMI and compare trajectories in relation to risk factors which can interact with obesity, such as deprivation, smoking, and medications. We will investigate how the longitudinal changes of BMI, including through interventions such as bariatric surgery or medications, may impact on the development of diseases and how BMI and the risk of cardiovascular diseases and cancers has changed over time. Associations with a single disease (monomorbidity) or multiple diseases (multimorbidity), as well as mortality, will be evaluated in both relative and absolute risks. Using time-to-first-event analysis, parametric (i.e., Royston-Parmar), semi-parametric (i.e., Cox), and non-parametric (i.e., Kaplan-Meier) survival analysis and multilevel models, and sensitivity analyses we will examine the association between obesity interventions, such as bariatric surgery and medications, on different risk factors and morbidity/mortality outcomes, exploring interactions by age, sex, ethnicity and deprivation, and develop models to predict the outcomes in relation to patients’ characteristics and medications/bariatric surgery. This study using the UK’s EHR data will lead to a better understanding of the factors that contribute to health of people in the UK.
(i) Fatal and non-fatal complications that have been deemed relevant in the investigations of obesity, including but not limited to cardiovascular and metabolic diseases and cancers.[1] The absolute and relative risks of these complications over time, as well as of mortality, will be estimated within individuals in relation to BMI, bariatric surgery, medical/drug interventions for obesity, and other individual level characteristics (including sociodemographic). (ii) Change in the risk factors before and after bariatric surgery and medical/drug interventions.
The main complications (primary outcomes) of interest are:
-Hypertension (also a risk factor)
-Type 2 diabetes (also a risk factor)
-Cause-specific and all-cause mortality
-Cardiovascular diseases (e.g., heart failure, myocardial infarction, atrial fibrillation, peripheral arterial disease)
-Cerebrovascular disease (e.g., stroke)
-Kidney disease
-Cancers
We will also investigate (secondary outcomes):
- Variations in lipid disorders (also a risk factor)
- Variations in glucose levels (also a risk factor)
-Variations in BMI/body weight over time
-Mental health (e.g., depression, anxiety)
-Neurological (e.g., dementia, Alzheimer’s disease, Parkinson’s disease)
-Respiratory (e.g., asthma, chronic obstructive pulmonary disease)
-Musculoskeletal (e.g., osteoporosis, rheumatoid arthritis)
Potentially some additional complications and risk factors could be included based on discussions with the study team which includes epidemiologists and clinicians working on research and treatment of obesity-related outcomes, to determine real world relevance in relation to obesity. Furthermore, we will be considering the rapidly evolving research area of multiple long-term conditions to define potentially relevant clinical conditions as complications/outcomes.
Francesco Zaccardi - Chief Investigator - University of Leicester
Suhail Shiekh - Corresponding Applicant - University of Leicester
Cameron Razieh - Collaborator - University of Leicester
Clare Gillies - Collaborator - University of Leicester
Kamlesh Khunti - Collaborator - University of Leicester
Navjot Kaur - Collaborator - University of Leicester
Sharmin Shabnam - Collaborator - University of Leicester
Tom Yates - Collaborator - University of Leicester
Yijing Chen - Collaborator - University of Leicester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation