Home Science Elevated Levels of a Certain Protein Increase Risk of Diabetes and Cancer Death

Elevated Levels of a Certain Protein Increase Risk of Diabetes and Cancer Death

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This protein may predict future cancer mortality and diabetes risk.

A Swedish study of about 4,000 people over 22 years found that those in the top quartile of blood prostasin levels were 76% more likely to develop diabetes and 43% more likely to die of cancer. It turned out to be expensive.

A recent study found that people with high levels of the protein prostasin, a protein found primarily in epithelial cells that line the surface of the body and organs, may be more likely to develop diabetes. DiabetesJournal of the European Diabetes Society (EASD).

Importantly, the results also suggest that people with high blood sugar and prostasin levels appear to be much more likely to die from cancer.

Findings were consistent even after considering a variety of important variables, including age, gender, waist circumference, drinking and smoking patterns, LDL (bad) cholesterol, systolic blood pressure, and antihypertensive medications.

The Malmö Diet and Cancer Study is a large, population-based, prospective study that has been ongoing since 1993 in the southern Swedish city of Malmö, a source of blood samples for research and a study of prostasin and blood in the general population. Moderate concentrations and cancer mortality.

“This is the most comprehensive analysis to date and sheds new light on the biological relationship between diabetes and cancer,” said co-lead author Gunnar Engström, Lund University, Malmö, Sweden. the professor said. “Prostasin could be just an indicator that a disease is likely to develop or may be causal. It is exciting because it increases the likelihood of targeting

Numerous studies have shown an association between diabetes and increased susceptibility to various cancers as well as increased mortality from cancer. Diabetes drugs can also alter this correlation. People with type 2 diabetes have a 30% higher risk of colorectal cancer and a 20% higher risk of breast cancer, plus about 2 more chances of developing pancreatic, endometrial, and liver cancer will double. However, little is known about the mechanisms behind this predisposition.

Prostasin is a stimulator of epithelial sodium channels that regulate sodium balance, blood volume, and blood pressure. In addition, prostasin has been shown to inhibit hyperglycemia (hyperglycemia)-induced tumor growth and is associated with glucose metabolism. However, little is known about the relationship between prostasin, diabetes, and cancer mortality.

To find out more, a team of researchers from China and Sweden measured blood prostasin levels (sorted by quartile) in 4,658 adults (mean age 58 years, 40% male) enrolled in the malmö diet. A cross-sectional analysis of the association between diabetes and diabetes was performed. In the cancer study cardiovascular cohort from 1991 to 1994, 361 (8%) had pre-existing diabetes.

After adjusting for potential confounders such as age, sex, waist circumference, smoking and drinking habits, LDL cholesterol, systolic blood pressure, and antihypertensive drugs, elevated prostasin levels are positively associated with the presence of diabetes. I understand. The highest prostasin quartile almost doubles the chance of developing diabetes compared to the lowest.

The researchers then examined clinical data from the same cohort (excluding 361 participants with pre-existing diabetes) through the end of 2019 to explore associations with new cases of diabetes. With an average follow-up of 22 years, 702 participants developed diabetes. Longitudinal analysis identified a linear relationship between prostasin and onset diabetes, with participants with prostasin in the highest quartile being 76% more likely to develop diabetes than participants in the lowest quartile. became.

Interestingly, prostasin levels were found to be better predictors of diabetes in younger participants and in participants with low blood sugar and good renal function. It is speculated that prostasin may be a compensatory response to excessively high blood sugar levels (hyperglycemia), but is insufficient to stop or reverse the deterioration of glycemic control. can be secreted in the urine, normal renal function helps maintain optimal prostasin blood levels.

In further analyzes examining whether prostasin affects mortality (by all-cause, cancer mortality, and cardiovascular mortality), the researchers found that prostasin was associated with cancer mortality and all-cause mortality. During the average 24-year follow-up period, 651 participants died of cancer. Participants in the highest quartile of prostasin blood levels were 43% more likely to die of cancer than participants in the lowest quartile. There was a 139% and 24% increased risk of cancer death in participants with and without elevated blood sugar (impaired fasting blood sugar), respectively. No association with cardiovascular mortality was seen.

“Prostasin is a new potential risk marker for diabetes development and cancer mortality, especially in people with high blood sugar,” said lead author Xue Bao, Ph.D., Nanjing University Hospital, Nanjing, China. said. “It’s easy access makes it more likely to serve as a warning marker in the future.”

Prostasin has a role in modulating several diabetes-related biological pathways that are also involved in the development and promotion of some cancers, thus potentially mediating the process of hyperglycemia to cancer. , at least may serve as a marker of cancer susceptibility.Participants with high blood glucose levels. To investigate this in more detail, tracing the exact origin of prostasin in the blood and determining whether the association between prostasin and diabetes is causal would be useful for future research. ”

The authors noted that the study was observational and pointed out some limitations, such as the study being limited by using a single dataset from one city in Sweden, hence the findings. points out that it may not be generalizable to other populations. They also found that prostasin levels were measured using frozen blood samples stored for more than 10 years, and the values ​​may not be the same as those measured in fresh samples. Only measuring prostasin levels at time points could not distinguish between types of diabetes.

Reference: “Plasma prostasin: A novel risk marker for diabetes and cancer mortality,” Xue Bao, Biao Xu, Iram Faqir Muhammad, Peter M. Nilsson, Jan Nilsson, and Gunnar Engström, 4 August 2022, Available here. Diabetes.
DOI: 10.1007/s00125-022-05771-w

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