Elevated levels of a certain protein in the blood may help pinpoint who is at higher risk for diabetes and cancer-related mortality, researchers report.
In a study of more than 4,000 Swedish adults, those in the highest quartile of plasma prostaglandin concentrations had almost as much risk of developing diabetes as those in the lowest quartile twice (adjusted OR 1.95, 95% CI 1.39-2.76, P
In addition to this, prostaglandin levels were also significantly associated with new-onset diabetes, and during a mean follow-up of 22 years, the group in diabetology .
Those in the highest quartile of prostaglandin concentrations had a 76% higher risk of developing diabetes (HR 1.76, 95% CI 1.41) -2.19 , P
Following a similar trend, higher prostaglandin levels in adults without diabetes were significantly associated with higher fasting blood glucose levels, plasma insulin levels, and insulin resistance as measured by HOMA2-IR .
In addition to diabetes, Engström’s group also found that plasma prostaglandins were associated with cancer mortality in this group of middle-aged adults.
Compared with the lowest quartile of prostaglandins, those in the highest quartile had a 43% higher mortality rate from cancer (HR 1.43, 95% CI 1.14-1.80). The association held even after people with cancer at baseline were excluded.
Interestingly, this association also interacted with fasting blood glucose. Among those with impaired baseline fasting glucose, the risk of cancer mortality was increased by 52% per 1 SD change in prostaglandins, whereas the risk per SD change in unimpaired glucose levels was only 11%.
“This is the most comprehensive analysis to date and sheds new light on the biological link between diabetes and cancer,” Gunnar explained in a statement. “Prostaglandins may simply be indicators that disease may occur or may be causally linked, which is exciting as it raises the possibility of targeting this protein in future treatments for diabetes and cancer.”
This protein has been recognized as a tumor biomarker as a stimulator of epithelial sodium channels.
“Several diabetes-related biological pathways, such as inflammation, endoplasmic reticulum stress, epithelial-mesenchymal transition, Akt signaling, and Wnt/β-catenin signaling, also involved in carcinogenesis, invasion or metastasis,” the researchers explained, adding that prostaglandins have a known role in regulating these pathways.
Having said that, they point out that prostaglandins may mediate the process from hyperglycemia to cancer, or may serve as markers of cancer susceptibility in people with elevated blood sugar.
“Prostaglandins may by then be considered therapeutic targets for diabetes and cancer if associations are established by chance in the future,” Gunnar’s group suggests.
A total of 4,658 people were included in the original cross-sectional analysis of the Malmö Diet and Cancer Study, which began in 1993. In this group, 361 (7.75%) had diabetes. About 40% of the cohort were men, with an average age of 58 years. After excluding those already diagnosed with diabetes, 702 developed diabetes during follow-up and 651 died of cancer.
Prostaglandin levels were measured from blood samples taken at baseline. For men, the highest quartile of prostaglandins averaged 8.93 µg/mL and the lowest quartile averaged 7.97 µg/mL. For women, the mean level in the highest quartile was 8.72 µg/mL and the lowest quartile was 7.62 µg/mL.
Diagnosis of diabetes was defined as two independent tests with a fasting blood glucose concentration of 126 mg/mL dL or higher plus a filled prescription for insulin or hypoglycemic medication.
Models based on age, gender, waist circumference, smoking and drinking habits, LDL cholesterol, systolic blood pressure, and antihypertensive medications.
Kristen Monaco is a staff writer focusing on endocrinology, psychiatry and nephrology news. She works out of the New York City office and has been with the company since 2015.
Disclosure
This research was supported by the Swedish Heart and Lung Fund, the National Natural Science Foundation of China, and the Natural Science Foundation of Jiangsu Province.
Package and co-author reports are not disclosed.
