Mortality Outcomes in People with Lung Cancer with and without Type2 Diabetes: A Cohort Study in England

Introduction: The impact of type 2 diabetes (T2DM) on mortality following lung cancer diagnosis remains unclear, with conflicting evidence across studies. We aimed to assess differences in all-cause and cause-specific mortality between people with lung cancer with and without T2DM within a primary care population in England. Methods: The study population was 69,674 people with incident lung cancer within the Clinical Practice Research Datalink (CPRD) Aurum primary care database (2010-2022). The study exposure was T2DM at cancer diagnosis, and the outcomes were all-cause and cause-specific mortality (cancer, cardio-vascular, respiratory). Cox models were fitted for each outcome adjusting for age, gender, smoking status, body mass index, calendar year and socioeconomic status (Index of Multiple Deprivation). Results: After adjusting for age and gender, there was no evidence for a difference in all-cause mortality in people with T2DM compared with people without T2DM (IRR 0.98 95% CI 0.96, 1.01). After fully-adjusting for measured confounders, there was a small positive effect (IRR 1.07 95% CI 1.04, 1.09). After adjusting for age and gender, people with T2DM had lower rates of cancer-specific mortality compared to people without T2DM (IRR 0.96 95% CI 0.94, 0.98). However, after adjustment for all measured confounders there was a small positive association (IRR 1.05 95% CI 1.02, 1.07). In both age and gender adjusted and fully adjusted models people with T2DM had higher cardiovascular (fully adjusted HR 1.30 95% CI 1.15, 1.47) and respiratory disease mortality (fully adjusted HR 1.30 95% CI 1.15, 1.47). Conclusion: There was robust evidence that people with T2DM had higher cardiovascular and respiratory disease mortality following lung cancer diagnosis. The relationships between T2DM and all-cause and cancer-specific mortality were highly sensitive to adjustment for confounding. Differences in studies on approaches to confounding and levels of missing data may contribute to the mixed findings on this association in the literature. Plain Language Summary: Lung cancer and type 2 diabetes are both common conditions that have a big impact on health outcomes worldwide. There is some evidence that people with type 2 diabetes have a higher chance of dying if they develop certain cancers than people without type 2 diabetes. It is not clear if having type 2 diabetes affects people's chances of dying if they develop lung cancer, or if any increased risk of death is due to lung cancer or other conditions such as heart disease. We used data from general practice records linked with hospital and death records from England to investigate whether people with diabetes were more or less likely to die following being diagnosed with lung cancer overall and from three specific causes of death: cancer, heart disease and lung disease. People with type 2 diabetes were more likely to die from heart disease and lung-related illnesses after being diagnosed with lung cancer than people without type 2 diabetes. However, differences in dying overall and of dying from cancer were small and depended on how other factors, like age and smoking, were considered. These findings highlight the importance of managing heart and lung health in people living with type 2 diabetes who are diagnosed with lung cancer.