Background People with Type 2 diabetes (T2D) are more susceptible to infections, and at greater risk of all-cause mortality, than the general population. We investigated risks associated with cause-specific mortality for infections among people with T2D compared to those without diabetes in a 5-year period prior to the COVID-19 pandemic.

Methods 509,403 T2D patients in England, aged 41-90 and alive on 01/01/2015 in the Clinical Practice Research Datalink, were matched to 2 patients without diabetes of the same age, sex and ethnicity. Deaths during 2015-9 were identified though linkage to Office of National Statistics mortality data, which provided cause of death information. Deaths were categorised into (i) infection as underlying cause (bone/joint, central nervous system, gastrointestinal, genitourinary, heart, lower respiratory, sepsis, skin/cellulitis, other), (ii) infection listed as a contributing cause only, (iii) all other causes. Cause-specific hazard ratios (HR) were estimated using Cox models adjusting for region, in addition to the matching factors. Models were fitted to different age groups as appropriate.

Results 85,523 (16.4%) people with T2D died during 2015-9 compared to 106,916 (10.7%) of people without diabetes. Among those who died, a slightly higher proportion of T2D patients had an infection listed as an underlying cause (13.0% vs. 12.0%). Additionally, a significant proportion listed sepsis as a contributing cause where the underlying cause was non-infective (3.2% T2D, 2.5% non-diabetes). The HR for all infective causes was 1.82 (95%CI 1.78-1.86) compared to HR=1.63 (95%CI 1.61-1.64) for all other causes.

Among the youngest (41-50 years) the difference between the estimated HR for T2D and infection death (HR=5.64, 95%CI 4.11-7.75) and T2D and non-infection deaths (HR=2.82, 95%CI 2.62-3.03) was most apparent. For specific types of infection, the largest HRs for T2D were seen among ages ≤70 years for rarer recorded causes such as bone/joint (HR=13.30) and skin/cellulitis (HR=8.79). Among all T2D deaths with skin/cellulitis as the underlying cause, 78% also had sepsis listed as a contributing cause.

Conclusion People living with T2D die from infections at a higher rate than people without diabetes. This is especially true at younger ages, and for specific types of infection, which may lead to further complications such as sepsis. Routine statistics concentrating on underlying cause of death may somewhat under-estimate the importance of infections as causes of death among people with T2D. These findings emphasise the higher risk of infection-related mortality associated with T2D, and the importance of awareness and earlier diagnosis and treatment.