New study reveals that infection-related deaths in type 2 diabetes are greatly 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 source: Dragana Gordic / Shutterstock
In a recent study published in The Lancet Regional Health – Europeresearchers quantified the burden of infection-related mortality in people with type 2 diabetes (T2D) compared with the general population, taking into account all recorded causes of death and sepsis.
Background
People with diabetes face an increased risk of infections and all-cause mortality compared to the general population. However, traditional assessments often underestimate infection-related mortality due to International Classification of Diseases, 10th Revision (ICD-10) coding structures that divide infections into several chapters or group them into broader categories such as respiratory diseases. Furthermore, sepsis, a critical infection-related complication, is rarely reported as the underlying cause of death despite its increasing prevalence among people with diabetes. For example, in only 11% of reported deaths was sepsis recorded as the underlying cause, highlighting systematic underreporting. Limited research has investigated infection-related mortality patterns by ethnicity or considered younger populations with T2D. Further research is needed to identify preventable deaths and to address disparities in infection-related mortality.
About the study
The present study used a February 2022 extract from the Clinical Practice Research Datalink (CPRD) Aurum database, which includes approximately 16 million active patients from 1,447 general practices in England. Over 90% of participating practices agreed to link their data with external sources such as Office for National Statistics (ONS) mortality data and the Index of Multiple Deprivation (IMD), an indicator of socio-economic status. Researchers did not have access to geographic identifiers.
The study used a matched cohort design that compared people with T2D to people without diabetes. Participants aged 41–90 years with a diagnosis of diabetes were identified and matched to nondiabetic individuals by age, sex, and ethnicity, resulting in 509,403 individuals with T2D and 976,431 matched comparators. Mortality data from 2015-2019 were categorized into specific causes, such as cancer, cardiovascular disease, respiratory disease, dementia, diabetes, digestive disorders and infections, using ICD-10 codes.
Cox proportional hazard models estimated 5-year mortality risk, adjusting for relevant factors and practice areas. Sensitivity analyzes 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 underreporting when relying on traditional classifications.
Study results
Among 509,403 subjects with T2D and 976,431 matched subjects 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 greater proportion was in the most deprived socio-economic areas (23% vs. 16%). About 34% of people with T2D were diagnosed in the last five years.
During the study period (2015-2019), 16.8% of people with diabetes died compared to 10.9% of people without diabetes, yielding a hazard ratio (HR) of 1.65. The excess relative risk was particularly pronounced among younger individuals aged 41–60 years, with an HR nearly four times higher in this group compared with their nondiabetic counterparts. Women with T2D had a slightly higher HR (1.71) than men (1.61), although the 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 Blacks (1.48). White subjects consistently showed larger absolute mortality differences in the 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 with non-diabetic subjects, subjects with T2D showed a higher HR for cardiovascular mortality (2.00), digestive diseases (1.98) and infections (1.82). Sensitivity analyzes adjusted 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. Considering all infection-related codes in the chapters, the study showed that infections accounted for 13% of T2D deaths, a marked increase from the 1.2% recorded in conventional ICD-10 categories. The highest HR for infections was seen in bone and joint infections (3.95), while lower respiratory tract infections, particularly pneumonia, contributed to 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% were listed as the underlying cause. Including any report of sepsis increased the HR to 2.26. This discrepancy highlights the critical need to recognize sepsis as an important contributor to mortality among individuals with T2D. 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), highlighting the vulnerability of this population to specific infections.
conclusions
In summary, this study highlights the underestimated burden of infection-related mortality in people with T2D, with infections contributing to 13% of deaths compared to 1.2% according to traditional ICD-10 classifications. The study also revealed significant disparities, including larger absolute mortality differences in white populations and increased risks among younger people with T2D. Sepsis, often underreported as an underlying cause, contributed significantly. Public health efforts should prioritize infection prevention, early diagnosis, and treatment to reduce premature deaths and alleviate economic and social burdens.
