Plasma prostaglandins are associated with the incidence of diabetes

A 22-year Swedish survey of nearly 4,000 people found that people in the top quartile of blood levels were 76 percent more likely to develop diabetes and 43 percent
more likely to die from cancer.

According to recent studies, those with elevated levels of prostaglandins, which are mainly found in epithelial cells that line the surface and organs of the body, may be more susceptible to diabetes
.
The study was recently published in
the journal Diabetologia, the European Association for the Study of Diabetes (EASD).

Importantly, the findings also suggest that people with higher blood sugar and prostaglandin levels appear to have a much higher
chance of dying from cancer.

Even after accounting for a variety of important variables such as age, gender, waist circumference, drinking and smoking patterns, LDL (bad) cholesterol, systolic blood pressure, and antihypertensive medications, the findings were consistent
.

This large-scale, population-based prospective study, which has been conducted in southern Sweden since 1993, had blood samples from the study, which was the first to examine the relationship between
prostaglandin blood levels and cancer mortality in the general population.
        

"This is the most comprehensive analysis of its kind to date and provides new clues to the biological link between diabetes and cancer," said
co-lead author from Lund University in Sweden.
"It is exciting that prostaglandins may just be an indicator of what the disease may be likely to do, or that may be causally related, because it raises the possibility of
future treatments for diabetes and cancer targeting this protein.
"

Numerous studies have shown an association
between diabetes and a higher risk of developing various cancers and a higher cancer mortality rate.
Diabetes medications can also change this correlation
.
In addition to a 30% increased risk of bowel cancer and a 20% increased risk of breast cancer, people with type 2 diabetes are twice as
likely to develop pancreatic, endometrial and liver cancers than other diseases.
However, little
is known about the mechanisms behind this tendency.

Prostaglandins are stimulators of epithelial sodium channels, regulating sodium balance, blood volume, and blood pressure
.
In addition, prostaglandins have been found to inhibit hyperglycemia (hyperglycemia)-induced tumor growth and are involved in
glucose metabolism.
However, little is known about the link between prostaglandins, diabetes and cancer
mortality.

To learn more, a team of Chinese and Swedish researchers looked at 4658 adults (mean age 58; 40% of men) of which 361 (8%) had diabetes were surveyed
.

After adjusting for potential confounding factors including age, sex and waist circumference, smoking and drinking habits, LDL cholesterol, systolic blood pressure and antihypertensive drugs, elevated prostaglandin levels were found to be positively correlated with the presence of diabetes, with the highest quartile of prostaglandin levels almost twice as likely to develop diabetes as
the lowest.

The researchers then examined clinical data from the same cohort (excluding 361 participants with pre-existing diabetes) before the end of 2019 to investigate correlations with new cases of diabetes
.
At an average follow-up of 22 years, 702 participants developed diabetes
.
Longitudinal analysis found a linear relationship between prostaglandins and the onset of diabetes, with the highest quartile of participants 76%
more likely to develop diabetes than the lowest quartile.

Interestingly, the study found that prostaglandin levels were better predictors of diabetes
in younger participants as well as those with lower blood sugar levels and better kidney function.
The authors speculate that elevated prostaglandin levels may be a compensatory response to high blood sugar (hyperglycemia), but may not be enough to stop or reverse worsening blood sugar control
.
Since prostaglandins may be secreted into the urine, normal kidney function may help maintain optimal blood levels of
prostaglandins.

In further analysis of whether prostaglandins have an effect on mortality (any cause, cancer mortality and cardiovascular mortality), the researchers found that prostaglandins were significantly associated
with cancer mortality and all-cause mortality.
At an average follow-up of 24 years, 651 participants died of cancer
.
The participants with the highest blood levels of prostaglandins were 43 percent
more likely to die of cancer than the participants with the lowest levels of prostaglandins in their blood.
For every doubling of prostaglandin concentration, the risk of cancer death increased by 139 percent and 24 percent
, respectively, in participants with elevated and no elevated blood sugar (impaired fasting blood sugar).
No association
with cardiovascular mortality was found.

Dr Xue Bao, from the Affiliated Hospital of Nanjing University School of Medicine in China, said: "Prostaglandins are a new potential risk marker for diabetes development and cancer mortality, especially in
individuals with high blood sugar levels.
It is readily available, which enhances its potential
as a warning sign in the future.
”

Because prostaglandins play a role in regulating several diabetes-related biological pathways that are also involved in the development and promotion of some cancers, it may potentially mediate the process from hyperglycemia to cancer, or at least as markers of
cancer susceptibility in participants with hyperglycemia.
To investigate this in more detail, it will facilitate future research to track down the exact origin of prostaglandins in the blood and determine if there is a causal relationship
between prostaglandins and diabetes.
”

The authors note that the study was observational and point out some limitations, including that the study was limited by the use of a dataset from one city in Sweden, so the findings may not be generalizable to other populations
.
They also noted that prostaglandin levels were measured with frozen blood samples stored for more than a decade, and their values may differ from
those measured in fresh samples.
In addition, the study measured prostaglandin levels at only one time point and did not distinguish between diabetes types
.

Reference: Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality