Deadly Cancer Cells Rendering

High levels of a certain protein increase the risk of diabetes and death from cancer

The protein could potentially predict future risk of death from cancer and diabetes.

A Swedish survey of nearly 4,000 people over the age of 22 found that those with prostasin blood levels in the top quartile were 76% more likely to develop diabetes and 43% more likely to die from diabetes. cancer.

According to recent research, those with high levels of prostasin, a protein found primarily in epithelial cells that line body surfaces and organs, may be more susceptible to developing diabetes. This research has just been published in Diabetologythe journal of the European Association for the Study of Diabetes (EASD).

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

Even after taking into account a variety of important variables, such as age, gender, waist circumference, drinking and smoking habits, LDL (bad) cholesterol, systolic blood pressure and antihypertensive drugs, the results remained consistent.

The Malmö Diet and Cancer Study, a large prospective population-based 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 and sheds new light on the biological link between diabetes and cancer,” says co-lead author Professor Gunnar Engström of Lund University in Malmö, Sweden. “Prostasin may just be an indicator that disease might be occurring, or might be causally relevant, which is exciting because it raises the possibility of targeting this protein with future treatments for diabetes and cancer.”

Numerous studies have shown a link between diabetes and a higher risk of contracting various cancers as well as a higher death rate from cancer. Diabetes medications can also alter this correlation. In addition to having a 30% increased risk of bowel cancer and 20% increased risk of breast cancer, people with type 2 diabetes are about twice as likely to get cancer of the pancreas, endometrium and liver. However, little is known about the mechanisms behind this predisposition.

Prostasin is a stimulator of epithelial sodium channels which regulate sodium balance, blood volume and blood pressure. Additionally, prostasin has been found to suppress tumor growth induced by hyperglycemia (high blood sugar) and is associated with glucose metabolism. However, little is known about the link between prostasin, diabetes and cancer mortality.

To find out more, a team of Chinese and Swedish researchers conducted a cross-sectional analysis of the association between blood prostasin levels (ranked by quartiles) and diabetes in 4,658 adults (mean age 58 years; 40% men ) enrolled in the Malmö scheme. and Cancer Study Cardiovascular Cohort between 1991 and 1994, of whom 361 (8%) had existing diabetes.

After adjusting for potential confounders including age, sex, and waist circumference, smoking and alcohol consumption habits, LDL cholesterol, systolic blood pressure, and antihypertensive medications, 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 be diabetic as those in the lowest quartile.

The researchers then looked at clinical data from the same cohort (excluding 361 participants with existing diabetes) through the end of 2019 to investigate associations with new cases of diabetes. During an average follow-up of 22 years, 702 participants developed diabetes. Longitudinal analyzes identified a linear relationship between prostasin and incident diabetes, with participants with prostasin in the highest quartile being 76% more likely to develop diabetes than those in the lowest quartile.

Interestingly, prostasin levels were found to be a better predictor of diabetes in younger participants and in those with lower blood sugar and better kidney function. The authors speculate that elevated prostasin levels may be a compensatory response to too high blood sugar (hyperglycemia), but may be insufficient to halt or reverse deterioration in blood sugar control. And because prostasin can be secreted in the urine, normal kidney function can help maintain optimal prostasin blood levels.

In further analyzes examining whether prostasin has an effect on mortality (all-cause, cancer mortality, and cardiovascular mortality), the researchers found that prostasin was significantly associated with both cancer mortality and all-cause mortality. combined causes. During an average follow-up of 24 years, 651 participants died of cancer. Participants with blood prostasin levels in the highest quartile were 43% more likely to die of cancer than those in the lowest quartile. For each doubling of prostasin concentration, the risk of cancer mortality increased by 139% and 24%, respectively, in participants with and without high blood sugar (impaired fasting blood sugar). No association was found for cardiovascular mortality.

“Prostasin is a potential new risk marker for the development of diabetes and cancer mortality, especially in people with high blood sugar,” says first author Dr. Xue Bao of Faculty Affiliated Hospital. of Medicine from Nanjing University in Nanjing, China. “It is easily accessible, which enhances its potential to serve as a warning marker in the future.”

Since prostasin plays a role in regulating several biological pathways associated with diabetes that are also implicated in causing and promoting certain cancers, it may potentially mediate the process from hyperglycemia to cancer, or at least may act as a marker for cancer susceptibility in participants with high blood sugar. To examine this in more detail, it will be useful for future studies to trace the exact origins of prostasin in the blood and to determine if the association between prostasin and diabetes is causal.

The authors note that the study is observational and point out several limitations, including that the study is limited by its use of a dataset from a Swedish city, therefore the results might not be generalizable to d other populations. They also note that prostasin levels have been measured using frozen blood samples stored for more than a decade and their values ​​may not be the same as those measured in fresh samples. Additionally, the study only measured prostasin levels at one time point and could not distinguish between types of diabetes.

Reference: “Plasma Prostasin: A New Risk Marker for Diabetes Incidence and Cancer Mortality” by Xue Bao, Biao Xu, Iram Faqir Muhammad, Peter M. Nilsson, Jan Nilsson, and Gunnar Engström, August 4, 2022, Diabetology.
DOI: 10.1007/s00125-022-05771-w

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