A new study published has just identified a new potential risk predictor of diabetes in younger participants, and those with lower blood glucose levels and better kidney function.

New research published in Diabetologia, indicates that people with high levels of the protein prostasin, which is mostly found in the epithelial cells that line the surfaces and organs of the body, may be more likely to get diabetes.

Importantly, the results also suggest that people with raised blood sugar and prostasin levels appear to have a much higher risk of dying from cancer.

Even after accounting for a variety of important variables, such as age, sex, waist size, drinking and smoking patterns, LDL (bad) cholesterol, systolic blood pressure, and anti-hypertensive medication, the results remained consistent.

The Malmö Diet and Cancer Study, a sizable population-based prospective study that has been ongoing in Malmö, a city in southern Sweden, since 1993, was the source of blood samples for the study, which is the first to examine the relationship between prostasin blood levels and cancer mortality in the general population.

“This is the most comprehensive analysis of its kind to date,” according to co-lead author Professor Gunnar Engström, “and sheds new light on the biological connection between diabetes and cancer.”

“Prostasin,” the author adds, “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.”

Diabetes is linked to an increased risk of getting several types of cancer and dying from cancer, and medicines used to treat high blood sugar can change this relationship. Type 2 diabetics have a 20% higher risk of breast cancer, a 30% higher risk of bowel cancer, and a roughly 2-fold increased risk of pancreatic, endometrial, and liver cancer. But we don’t know much about the mechanisms that cause this tendency.

Prostasin stimulates the epithelial sodium channels that control blood volume, blood pressure, and sodium balance.

Additionally, prostasin is linked to glucose metabolism and has been shown to inhibit the growth of tumors that are produced by hyperglycemia (high blood sugar).

But not much is known about how prostasin, diabetes, and cancer deaths are linked.

In order to learn more, a group of Chinese and Swedish scientists performed a cross-sectional analysis of the relationship 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 pre-existing diabetes.

After adjusting for possible confounding factors like age, sex, waist circumference, smoking and drinking habits, LDL-cholesterol, systolic blood pressure, and anti-hypertensive medication, it was found that high prostasin levels were linked to diabetes. People in the highest prostasin quartile were almost twice as likely to have diabetes as those in the lowest prostasin quartile.

After that, the researchers investigated possible correlations with newly diagnosed instances of diabetes by analyzing clinical data from the same cohort up until the end of 2019 (but removing data from 361 persons who already had diabetes).

Over the average follow-up time of 22 years, 702 participants got diabetes. When looking at long-term data, researchers found that people with the highest prostasin levels were 76% more likely to acquire type 2 diabetes than those with the lowest levels.

Prostasin levels, on the other hand, were found to be a better predictor of diabetes in younger participants, as well as those with lower blood glucose levels and better kidney function. The authors hypothesize that increasing prostasin levels may represent a compensatory reaction to excessively high blood sugar (hyperglycemia), but that this response may not be adequate to prevent or reverse deteriorating glucose control. Additionally, as prostasin may be excreted in the urine, healthy kidney function may aid in preserving the ideal level of prostasin in the blood.

In additional analyses assessing the influence of prostasin on mortality (from any cause, cancer mortality, and cardiovascular mortality), researchers discovered that prostasin was substantially related to both cancer mortality and all-cause mortality.

651 participants died of cancer throughout an average follow-up of 24 years.

Participants with blood levels of prostasin in the highest quartile had a 43 percent greater chance of dying from cancer than participants in the lowest quartile.

Participants with and without raised blood glucose levels saw 139 percent and 24 percent increases in cancer mortality risk for every doubling of prostasin concentration, respectively (impaired fasting glucose).

No link was found between heart disease and death.

“Prostasin is a new potential risk marker,” adds first author Dr Xue Bao, “for the development of diabetes and for cancer mortality, especially in individuals with high blood glucose levels. 

“It is easily accessible, which enhances its potential to serve as a warning marker in the future.”

Prostasin may potentially mediate the process from high blood sugar to cancer, or at the very least, it may act as a marker for cancer susceptibility in participants with high blood sugar, as it regulates several diabetes-associated biological pathways that are also involved in the onset and promotion of some cancers.

Future research on this topic will be helpful in tracing the precise sources of prostasin in blood and figuring out whether the link between prostasin and diabetes is real.

The study’s use of a single dataset from a single Swedish city, among other restrictions, means that the findings may not be generalizable to other populations, according to the authors, who also stress that the study is observational.

They further point out that since prostasin levels were determined using frozen blood samples that had been kept for more than ten years, their measurements might not be accurate.

Additionally, the study could not differentiate between different forms of diabetes because it only evaluated prostasin levels at one point in time.

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