Type 2 diabetes and cancer are conditions that can commonly occur together. Excess weight or obesity, commonly measured using body mass index, is associated with the development of Type 2 diabetes and several types of cancers, collectively known as obesity-related cancers.
In turn, diabetes is associated with the development of several common obesity-related cancers, including bowel, kidney, womb and liver cancer, but it is unclear whether this link is driven by obesity.
We have previously shown that, compared with people without diabetes, Type 2 diabetes is associated with a higher death rate overall. The main cause of death in these patients is heart disease, followed by death from cancer.
In this project, we will explore this link further. First, we will test whether the higher cancer death rate among patients with Type 2 diabetes is due to deaths from obesity-related cancers. Second, among patients with Type 2 diabetes, test that increasing body mass index is related to increasing deaths from obesity-related cancers.
If these questions are both true, this will suggest that excess weight in patients with Type 2 diabetes should be avoided to reduce cancer-related deaths. This will be a further rationale for weight management in these patients.
This application is a direct extension of an already captured matched cohort study of patients registered with diabetes in CPRD (protocol: 15_123Mn)
In the above study (Wright et al. Diabetes Care 2017;40:1-8), there were 187,968 patients with incident type 2 diabetes, T2D, (1998 to 2015) matched to 908,016 control subjects. Deaths were captured through linkage with Official of National Statistics.
Overall mortality was twofold greater among patients with T2D compared with those without diabetes. The commonest cause of increased mortality was circulatory disease (15.9 per 1000 py versus 6.4 per 1000 py); the second commonest cause was malignant neoplastic disease (11.0 per 1000 py versus 5.8 per 1000 py).
We will deeply phenotype the associations between T2D and the observed increased cancer-related mortality and explore the hypothesised central role of excess weight – approximated as body mass index (BMI).
We will use Cox proportional hazard models, stratified by matching group, to estimate hazard ratios and test that the higher cancer death rate among patients with T2D is due to deaths from obesity-related cancers (13 cancer types). And second, among patients with T2D, test that increasing BMI (determined in the peri-diagnosis of diabetes period) is related to increasing deaths from obesity-related cancers.
Darren Ashcroft - Chief Investigator - University of Manchester
Nasra Alam - Corresponding Applicant - University of Manchester
Alison Wright - Collaborator - University of Manchester
Andrew G Renehan - Collaborator - The Christie NHS Foundation Trust
Iain Buchan - Collaborator - University of Manchester
Martin Rutter - Collaborator - University of Manchester
Matthew Sperrin - Collaborator - University of Manchester
Tjeerd van Staa - Collaborator - University of Manchester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation