Warning on Risk of Serious Infections in Those With Diabetes

People with diabetes are at increased risk of hospitalization for infection, as well as infection-related mortality, shows a large US study that suggests the risk is even higher in younger and Black individuals.

Michael Fang, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues studied more than 12,000 participants in a community cohort study who were followed for an average of 24 years, between 1987-1989 and 2019.

Participants with diabetes faced a 67% increase risk of infection-related hospitalization compared with those without diabetes.

Of particular note, the risk of hospitalization with foot infection was almost sixfold higher for people with diabetes than those without.

The research, published in Diabetologia on August 4, also suggests that diabetes may be associated with a 72% increased risk of infection-related mortality, although the absolute numbers were small.

Fang explained to Medscape Medical News that they focused on infection-related hospitalization and mortality “because these are comprehensively tracked in administrative data and…are the most severe types of outcomes.”

However, this is probably just the tip of the iceberg, as people with diabetes are “likely at increased risk for milder infection too,” which can have a “significant adverse impact on people’s well-being and quality of life.”

As a result of their findings, the authors call for “broader guidance on infection prevention and management” in people with diabetes. To achieve this, Fang said, “we need to better understand why diabetes is associated with an increased risk of infection-related complications.”

“One likely factor is glycemic control: emerging research suggests patients with diabetes with better glycemic control may be at significantly lower risk of infection-related complications.”

He continued that, in younger patients, a factor for worse outcomes could be that “diabetes tends to be more aggressive when it emerges early in life,” while in Black patients “there is research highlighting Black–White differences in glycemic control, access to care, and beliefs around vaccines.”

Overall, their findings — coupled with recent data showing that diabetes is an important risk factor for adverse outcomes with COVID-19 infection — paint “a common picture,” Fang said.

“People with diabetes are much more susceptible to infection-related complications, including COVID-related hospitalization and mortality,” which suggests people with diabetes “may need to be especially cautious.”

Adds to Existing Literature; Amputations Begin With Infections

Robert A. Gabbay, MD, PhD, chief scientific and medical officer for the American Diabetes Association (ADA), said the study “does add to the existing literature by having followed a larger number of people over time and linking them to serious complications from infections.”

“Sadly, we have seen this play out in real-time during the COVID-19 pandemic.”

“One of the sobering bits of data is the significant health disparities that exist in Black Americans and the fact that foot infections remain a significant problem,” he told Medscape Medical News.

“Given that amputation rates for Blacks are three times higher than White Americans, amputations begin with infections,” Gabbay added, noting the ADA “has been taking a strong stand to prevent amputations and address the inequities in health that exist.”

Jamie Hartmann-Boyce, PhD, from the University of Oxford, UK, who was not involved in the study, commented that diabetes is a “well-known risk factor for worse outcomes from all kinds of infection,” which is why they “are prioritized for flu vaccination every year.”

She told Medscape Medical News that the current study “further confirms that people with diabetes are more likely to be hospitalized for infection of any type, and most markedly for foot infection.”

“These new data further highlight the need for public health interventions to prevent type 2 diabetes, and for preventive healthcare in people with diabetes, including access to diabetes medications and support, and to vaccinations to prevent infection,” added Hartmann-Boyce, who is a senior research fellow in health behaviors.

Diabetes is thought to be associated with susceptibility to infection via mechanisms such as impaired neutrophil functioning and humoral immune responses, and studies have shown a link with both common and rare infections.

However, the authors point out that “most” of those included “small clinical populations and were cross-sectional or had short follow-up.”

Guidelines for diabetes management, they note, also “pay less attention” to infectious diseases than they do to the prevention of micro- and macrovascular complications.

ARIC Data Mined for Infections in Those With Diabetes

The team analyzed data from the ongoing US community-based Atherosclerosis Risk in Communities (ARIC) study.

The National Heart, Lung, and Blood Institute-sponsored cohort was comprised of adults aged 45-64 years from four US communities, recruited between 1987 and 1989 for clinical examinations, medical interviews, and laboratory tests, repeated over five more visits up to 2018-2019.

For the current analysis, the team included 12,739 individuals with a mean age of 54.5 years, of whom 54.3% were female and 24.7% were Black.

Patients were defined as having diabetes if their baseline fasting blood glucose was ≥ 7 mmol/L, or nonfasting glucose was ≥ 11.1 mmol/l, or they self-reported a diagnosis of diabetes by a physician, or they were taking glucose-lowering medication at the first study visit. The researchers weren’t able to distinguish between type 1 and type 2 diabetes.

In total, 1485 individuals had diabetes at baseline. They were more likely to be older, Black, have a low socioeconomic status, and have worse cardiometabolic health than participants without diabetes.

Over an average follow-up of 23.8 years, there were 4229 incident hospitalizations for infection, at an overall rate of 15.9 per 1000 person-years.

Individuals with diabetes at baseline had a higher rate of hospitalizations than those without, at 25.4 per 1000 person-years versus 15.2 per 1000 person-years.

After taking into account sociodemographic characteristics, socioeconomic status, and cardiometabolic risk factors, this equated to a hazard ratio for hospitalization with any infection of 1.67 (P < .001).

The risk of hospitalization for any infection was significantly higher for younger patients with diabetes, defined as aged < 55 years (P = .005), and for Black patients (P < .001).

While the increased risk was generally consistent across infection types, it was markedly increased for foot infection, at a hazard ratio of 5.99 (P < .001).

Overall, there were few deaths due to infection in the study, at just 362. The risk of infection mortality was nevertheless significantly increased in people with diabetes, at an adjusted hazard ratio of 1.72 (P < .001).

Fang has reported being supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute. Selvin has reported being supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Selvin is an associate editor for Diabetologia and had no role in the peer review of the manuscript.

Diabetologia. Published online August 4, 2021. Full text

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