Longitudinal analyzes identified a linear relationship between prostasin and incident diabetes.
New research suggests that people with high levels of the protein prostasin, which is found primarily in epithelial cells that line body surfaces and organs, may be at higher risk of developing diabetes. European Association for the Study of Diabetes (EASD).
In addition, the results also indicate that people with high blood sugar and prostasin levels appear to have a significantly increased risk of die of cancer. The results held even after adjusting for a wide range of influencing factors, including age, gender, waist circumference, smoking and alcohol consumption habits, LDL (bad) cholesterol, systolic blood pressure and blood pressure. antihypertensive drug.
The study is the first to examine the relationship between blood prostasin levels and cancer mortality in the general population and analyzes blood samples from more than 4,000 middle-aged Swedish adults taken more than a decade ago. under the Malmö Diet and Cancer Studya large population-based prospective study that has been conducted in Malmö, a city in southern Sweden, since 1993.
“This is the most comprehensive analysis of its kind to date and sheds new light on the biological link between diabetes and cancer,” says study co-author Professor Gunnar Engström of Lund University. this could be causally relevant, which is exciting as it raises the possibility of targeting this protein with future diabetes treatments like for cancer.
Diabetes and cancer relationship
There is considerable evidence that diabetes is associated with an increased risk of developing and dying from various types of cancer, and that drugs used to treat high blood sugar may alter this association.
People with type 2 diabetes are about twice as likely to develop pancreatic, endometrial and liver cancers, have a 30% higher risk of develop bowel cancer and a 20% increased risk of breast cancer. However, the mechanisms underlying this predisposition are poorly understood.
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 rrelationship 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 Cancer and Diet Study Cardiovascular Cohort between 1991 and 1994, of whom 361 (8%) had diabetes.
After adjusting for potential confounders, such as age, sex and waist circumference, smoking and alcohol consumption habits, LDL cholesterol, systolic blood pressure and antihypertensive drughigh prostasin levels were found to be positively associated with the presence of diabetes, and those in the highest prostasin quartile were almost twice as likely to have diabetes as those in the lowest.
Next, the researchers looked at clinical data from the same cohort (excluding 361 participants with existing diabetes) through the end of 2019 to investigate associations with new diabetes. During a median follow-up of 22 years, 702 participants developed diabetes.
The bone 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 a better predictor of diabetes in younger participants and those who had drop in 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. Additionally, since prostasin can be secreted in the urine, normal kidney function can help maintain optimal blood levels of prostasin.
In other analyzes that looked at whether prostasin had an effect on mortality (all-cause, cancer mortality, and cardiovascular mortality), the researchers found that prostasin was significantly associated with both cancer and all-cause mortality. confused. During a median 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 death increased by 139% and 24%, respectively, in participants with and without high blood sugar (impaired fasting blood sugar). No relationship was found with cardiovascular mortality.
Regulation of biological pathways associated with diabetes
“Prostasin is a potential new risk marker for the development of diabetes and cancer mortality, especially in people with high blood sugar,” said first author Dr. Xue Bao, Affiliated Hospital of Nanjing University School of Medicine, China. It is easily accessible, which increases its potential to serve as a red flag in the future.”
Since prostasin is involved in the regulation of several biological pathways associated with diabetes that are also involved in the development and promotion of certain cancers, it could be involved in the process that goes from cancerous hyperglycemiaro, at least, act as a marker of cancer susceptibility in participants with hyperglycemia.
“To explore this in more detail, it will be useful for future studies to trace the exact origins of prostasin in the blood and to determine whether the association between prostasin and diabetes is causal,” the researchers note.
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