Younger adults and men with type 2 diabetes face higher risk of sepsis

Living with type 2 diabetes (T2D) may double the risk of developing sepsis-with those aged younger than 60 years and men particularly susceptible, according to a long-term community-based study in Australia, being presented at this year's Annual Meeting of The European Association for the Study of Diabetes (EASD), Vienna (15-19 Sept).

An association between type 2 diabetes and sepsis has been noted in some earlier studies. Our study, in a large community-based sample of adults, confirms a strong relationship even after adjustment for a number of potential risk factors and the competing risk of death from unrelated causes, which may have occurred in people at high risk of sepsis before they developed sepsis, thus leading to overestimation of the incidence of sepsis if ignored."

Professor Wendy Davis, lead author, University of Western Australia, Australia

She added, "The best way to prevent sepsis is to quit smoking, normalise high blood sugar, and prevent the onset of the micro- and macrovascular complications of diabetes. That's why this study is important."

Sepsis can occur as a result of any type of infection, and refers to a severe, life threatening, uncontrolled response to infection that can lead to organ failure and critical illness. More than 10% of people who develop sepsis die, and it is a leading cause of death worldwide.

Previous studies have found that people living with T2D have a 2- to 6-fold increased risk of sepsis and worse associated illness and death compared to people without diabetes, but contemporary data are limited.

To plug this knowledge gap, Australian researchers explored the incidence of sepsis in a community-dwelling cohort of people taking part in The Fremantle Diabetes Study Phase II-a longitudinal observational study conducted in a multi-ethnic urban community of 157,000 in Australia.

Researchers identified 1,430 adults with T2D at the time they enrolled between 2008 and 2011 who were matched with 5,720 de-identified individuals without T2D based on age, sex, and postcode. The average age of the participants at enrolment was 66 years, and 52% were men.

Their health was tracked, using linked health records, until the first record of incident sepsis, new onset diabetes (in the matched cohort), death, or the end of 2021, whichever came first.

At enrolment, 2.0% of those with T2D had a prior hospitalisation for/with sepsis versus 0.8% of their matched counterparts without diabetes. During an average 10 years of follow-up, 169 (11.8%) participants with T2D and 288 (5.0%) of their matched counterparts developed sepsis.

After adjustment for potential confounders including age, sex, prior hospitalisation for sepsis and having other chronic conditions, T2D was associated with double the risk of developing sepsis.

Notably, in those aged 41-50 years, having T2D was associated with a 14.5-fold increased risk of developing sepsis (see figure in notes to editors).

Further analysis revealed that among adults with type 2 diabetes, being older, male, from Aboriginal ancestry, current smoking, using insulin, having elevated fasting glucose and a higher heart rate, distal symmetrical polyneuropathy (nerve disease), cerebrovascular disease, and higher levels of the heart failure biomarker NT-proBNP, were all independently associated with higher risk of developing sepsis.

For example, Indigenous Australians with T2D were three times as likely to develop sepsis, while smoking was associated with an 83% increased risk of sepsis.

"Our study identifies several modifiable risk factors, including smoking, high blood sugar, and complications of diabetes, underscoring that there are steps individuals can take to potentially lower their risk of sepsis," said Professor Davis.

Several possible pathways may explain the association between type 2 diabetes and sepsis, including that elevated blood sugar levels lead to impaired immune function, and individuals with diabetes are also more prone to specific types of infections like urinary tract infections, skin infections, and pneumonia that can readily escalate into sepsis. Vascular damage and neuropathy, both common complications of diabetes, further contribute to the heightened sepsis risk. 

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge that there might have been other unmeasured factors that may have influenced the results. The researchers also note that participants may have been healthier than non-participants and they did not take into account changes in the management of diabetes during follow-up, which could partially affect the conclusions.