Middle aged man with type 2 diabetes using blood sugar measurement device to monitor type 2 diabetes, which can be treated with the GLP-1 receptor agonist semaglutide
Credit: Elva Etienne/Getty Images

A team of Swedish and Chinese researchers suggests that people with elevated levels of the protein prostasin are at higher risk of developing Type 2 diabetes, and that people with both elevated levels of the protein and high blood sugar are at significantly greater risk of dying from cancer.

The new research was published in Diabetologia—the journal of the European Association for the Study of Diabetes (EASD)—and found that these results remained consistent even after adjusting for a wide range of factors that contribute to the these diseases including age, sex, waist circumference, smoking and drinking habits, LDL cholesterol, systolic blood pressure, and anti-hypertensive medication.

“This is the most comprehensive analysis of its kind to date and sheds new light on the biological connection between diabetes and cancer,” says co-lead author Professor Gunnar Engström, M.D., Ph.D., from Lund University in Malmö, Sweden. “Prostasin may be just an indicator that disease might occur, or could be causally relevant, which is exciting because it raises the possibility of targeting this protein with future treatments for both diabetes and cancer.”

Prior research has presented evidence that people who develop type 2 diabetes are at significantly greater risk of developing specific cancers and that medications that treat high blood sugar (sugar being the food for tumor growth) can alter this association. People with type 2 diabetes are twice as likely to develop pancreatic, endometrial, and liver cancers. They are also 30% more likely to develop bowel cancer, and 20% more likely to develop breast cancer.

To begin developing a better understanding of the role of prostasin in diabetes development and cancer, the researchers conducted a cross-sectional analysis of the association between prostasin blood levels (categorized by quartiles) and diabetes in 4,658 adults (average age 58 years; 40% men) enrolled in the Malmö Diet and Cancer Study Cardiovascular Cohort between 1991 and 1994, of whom 361 (8%) had existing diabetes.

The team adjusted for a number of factors known to associated with diabetes development, as noted above, and showed that elevated prostasin levels were found to be positively associated with the presence of diabetes, with those in the highest prostasin quartile almost twice as likely to have diabetes compared to the lowest.

Using this information, the team then examined the available clinical data through 2019 excluding the 361 people in the cohort who had developed diabetes since they enrolled in the study in the early 1990s, to better understand associations of new diabetes cases. Over an average 22-year follow up 702 people developed diabetes and longitudinal analysis of the data showed a linear relationship between prostasin and the development of diabetes. Those with the highest levels of prostasin were (in the highest quartile) were 76% more likely to develop the disease compare with those in the lowest quartile.

One interesting finding was that prostasin levels were a better predictor of diabetes in younger participants, and those with lower glucose levels and better kidney function. The research team hypothesizes that elevated prostasin may be a response to high blood sugar, but that it may not be enough to check the body’s worsening ability to control glucose levels.

In further analyses examining whether prostasin has an effect on mortality (from any cause, cancer mortality, and cardiovascular mortality), researchers found that prostasin was significantly associated with both cancer mortality and all-cause mortality, while no association was found for cardiovascular death. During average follow-up of 24 years, 651 participants died from cancer. Participants with prostasin blood levels in the highest quartile were 43% more likely to die from cancer than those in the lowest quartile. For each doubling of prostasin concentration, risk of cancer mortality increased by 139% and 24%, respectively, among participants with and without elevated levels of blood glucose.

“Prostasin is a new potential risk marker for the development of diabetes and for cancer mortality, especially in individuals with high blood glucose levels,” noted first author Xue Bao, Ph.D., from The Affiliated Hospital of Nanjing University Medical School in Nanjing, China. “It is easily accessible, which enhances its potential to serve as a warning marker in the future.”

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