Study finds death receptors can indicate future CVD, diabetes risk

A Swedish study of nearly 5,000 patients has proven the efficacy of death receptors as markers for type 2 diabetes and cardiovascular disease, according to research published in EBioMedicine.

Death receptors, which are cell surface receptors in the blood that can trigger cell death—a necessary function to maintain homeostasis in the body—are activated when, for instance, a white blood cell is done fighting an infection and needs to be eliminated, lead author Jan Nilsson, MD, and colleagues wrote in the study. Though death receptors play a key role in keeping the body balanced, they’ve also been implicated in heart-related conditions like cardiovascular disease (CVD) and diabetes mellitus.

The receptors can be measured in the blood, Nilsson et al. wrote, but haven’t been investigated in relation to CVD and type 2 diabetes, despite the fact that both arteriosclerosis and type 2 diabetes are associated with increased cell death.

Cells self-destruct when the body’s blood vessels and insulin-producing beta cells are under stress, which is the case when a patient has high blood sugar and blood fat levels.

“When the beta cells are damaged, the production of insulin decreases, which increases the risk of diabetes,” Nilsson said in a release from Lund University in Sweden, where he teaches. “The damage activates repair processes in the blood vessels. If these are not properly resolved, this usually leads to the development of plaque in the blood vessels. The formation of cracks in this plaque is the primary cause of myocardial infarction and stroke.”

The researchers analyzed a pool of 4,742 Swedish citizens after collecting their data for nearly 20 years. The team compared different risk factors, including age, BMI, blood fat levels, blood sugar and blood pressure, with different death receptors in each patient’s blood. Nilsson and colleagues focused on death receptors TNFR-1, TRAILR-2 and Fas.

What they found was striking: Levels of different death receptors in the blood were tied to different risk factors for CVD and stroke. The authors found that elevated levels of death receptors were common in diabetics, suggesting excess cell stress, and in non-diabetics, higher levels of death receptors were linked to an increased risk of CVD and developing diabetes.

“On the other hand, we could not see that the level of death receptors is linked to the risk of developing cardiovascular disease among diabetics, which is a paradox,” Nilsson said. “We don’t yet really understand why, but it could be the case that the level of biomarkers, i.e. death receptors, among diabetics is already very high.”

The researchers said their findings could be used to monitor ongoing tissue damage and assess risk in patients who might be prone to CVD or diabetes.

“This indicates that we could at an early stage get an idea of whether treatment of risk factors reduces damage to beta cells and blood vessel walls by monitoring the death receptors in the blood,” Nilsson said.