New study reveals infection-related deaths in type 2 diabetes are vastly underestimated, urging better prevention and reporting strategies.
Study: Contribution of infection to mortality in people with type 2 diabetes: a population-based cohort study using electronic records. Image Credit: Dragana Gordic / Shutterstock
In a recent study published in The Lancet Regional Health – Europe, researchers quantified the burden of infection-related mortality in people with type 2 diabetes (T2D) compared to the general population, accounting for all recorded causes of death and sepsis mentions.
Background
People with diabetes face a heightened risk of infections and all-cause mortality compared to the general population. However, traditional assessments often underestimate infection-related mortality due to the International Classification of Diseases, 10th Revision (ICD-10) coding structures that distribute infections across multiple chapters or group them under broader categories like respiratory disease. Additionally, sepsis, a critical infection-related complication, is rarely listed as the underlying cause of death despite its increasing prevalence among people with diabetes. For example, only 11% of deaths where sepsis was mentioned had it recorded as the underlying cause, highlighting systematic underreporting. Limited research has explored infection-related mortality patterns by ethnicity or considered younger populations with T2D. Further research is essential to identify preventable deaths and address disparities in infection-related mortality.
About the study
The present study utilized a February 2022 extract from the Clinical Practice Research Datalink (CPRD) Aurum database, comprising approximately 16 million active patients from 1,447 general practices in England. Over 90% of participating practices consented to link their data to external sources such as the Office for National Statistics (ONS) mortality data and the Index of Multiple Deprivation (IMD), a proxy for socio-economic status. Researchers had no access to geographical identifiers.
The study employed a matched cohort design comparing individuals with T2D to those without diabetes. Participants aged 41-90 years with a diabetes diagnosis were identified and matched to non-diabetic individuals based on age, sex, and ethnicity, resulting in 509,403 individuals with T2D and 976,431 matched comparators. Mortality data from 2015-2019 was categorized into specific causes, including cancer, cardiovascular disease, respiratory conditions, dementia, diabetes, digestive disorders, and infections, using ICD-10 codes.
Cox proportional hazard models estimated 5-year mortality risk, adjusting for matched factors and practice regions. Sensitivity analyses examined additional variables such as deprivation and smoking. To address underreporting, researchers analyzed infection-related mortality using expanded ICD-10 coding across chapters, revealing significant underestimation when relying on traditional classifications.
Study results
Among the 509,403 individuals with T2D and 976,431 matched individuals without diabetes, baseline characteristics highlighted notable differences. The mean age of the T2D group was 67.3 years, with 56% being male. Obesity (body mass index (BMI) ≥ 30) was more prevalent in the T2D group (50% vs. 22%), and a larger proportion resided in the most socio-economically deprived areas (23% vs. 16%). Approximately 34% of T2D individuals were diagnosed within the last five years.
During the study period (2015-2019), 16.8% of T2D individuals died compared to 10.9% of those without diabetes, yielding a hazard ratio (HR) of 1.65. The excess relative risk was particularly stark among younger individuals aged 41–60, with HRs nearly four times higher in this group compared to their non-diabetic counterparts. Women with T2D had slightly higher HRs (1.71) than men (1.61), although absolute differences in mortality rates were comparable (13.9 vs. 13.1 per 1,000 person-years). Ethnic differences were observed, with the highest overall HR in South Asians (1.73) and the lowest in Black individuals (1.48). White individuals exhibited consistently greater absolute mortality differences in younger age groups.
Cardiovascular disease was the leading cause of death in T2D (29.7%), followed by cancer (26.9%) and infections (13.0%), including pneumonia. Compared to non-diabetic individuals, T2D individuals exhibited higher HRs for cardiovascular mortality (2.00), digestive disease (1.98), and infections (1.82). Sensitivity analyses adjusting for deprivation, smoking, or using different statistical methods confirmed these results.
Infections were often underestimated as a cause of death when using traditional coding methods. By considering all infection-related codes across chapters, the study demonstrated that infections accounted for 13% of T2D deaths, a marked increase from the 1.2% recorded under conventional ICD-10 categories. The highest HR for infections was observed in bone and joint infections (3.95), while lower respiratory tract infections, especially pneumonia, contributed the largest absolute differences in mortality rates.
Sepsis was often a contributing rather than the underlying cause of death. Among T2D deaths where sepsis appeared on the death certificate, only 11% had it recorded as the underlying cause. Including any mention of sepsis increased its HR to 2.26. This discrepancy underscores the critical need to recognize sepsis as a significant contributor to mortality among T2D individuals. Younger individuals with T2D showed particularly high HRs for rare infections, such as bone and joint infections (HR = 9.71) and skin/cellulitis (HR = 6.95), underscoring the vulnerability of this population to specific infections.
Conclusions
To summarize, this study highlights the underestimated burden of infection-related mortality in individuals with T2D, with infections contributing to 13% of deaths compared to 1.2% under traditional ICD-10 classifications. The study also revealed significant disparities, including greater absolute mortality differences in White populations and heightened risks among younger individuals with T2D. Sepsis, often underreported as an underlying cause, was a significant contributor. Public health efforts should prioritize infection prevention, early diagnosis, and treatment to reduce premature deaths and alleviate economic and societal burdens.