Blood Protein May Help Predict Diabetes, Death From Cancer

Elevated levels of a type of protein in the blood may help pinpoint who is at a higher risk for diabetes and cancer-related mortality, researchers reported.

In a study of over 4,000 Swedish adults, the odds of prevalent diabetes was nearly twice as high for those who fell into the highest quartile of plasma prostasin concentrations versus those in the lowest quartile (adjusted OR 1.95, 95% CI 1.39-2.76, P<0.0001 for trend), according to Gunnar Engström, MD, PhD, of Lund University in Malmö in Sweden, and colleagues.

In addition to this, prostasin levels were also significantly tied to new-onset diabetes, over the span of an average 22-year follow-up, period, the group wrote in Diabetologia.

Compared with the lowest quartile prostasin concentrations, those falling into the highest concentrations had a 76% higher risk for developing incident diabetes (HR 1.76, 95% CI 1.41-2.19, P<0.0001 for trend).

Following a similar trend, higher prostasin levels in adults without diabetes were significantly tied with higher fasting blood glucose levels, plasma insulin levels, and insulin resistance measured by HOMA2-IR.

Beyond just diabetes, Engström’s group also found that plasma prostasin was associated with cancer mortality among this cohort of midlife adults.

Compared with the lowest quartile of prostasin, those falling into the highest quartile had a 43% higher risk for cancer mortality (HR 1.43, 95% CI 1.14-1.80). This association still held true even after those with cancer at baseline were excluded.

Interestingly, this association also interacted with fasting blood glucose. Among those with impaired fasting glucose at baseline, they saw a 52% higher risk for cancer mortality per 1 SD change in prostasin, versus only an 11% higher risk per 1 SD change for those without impaired glucose levels.

“This is the most comprehensive analysis of its kind to date and sheds new light on the biological connection between diabetes and cancer,” Gunnar explained in a statement. “Prostasin may be just an indicator that disease might occur, or could be causally relevant, which is exciting because it raises the possibility of targeting this protein with future treatments for both diabetes and cancer.”

This protein acts as an epithelial sodium channel stimulator and is already regarded as a tumor biomarker.

“Several diabetes-associated biological pathways, such as inflammation, endoplasmic reticulum stress, the epithelial-to-mesenchymal transition, Akt signalling and Wnt/β-catenin signalling, also participate in carcinogenesis, invasion or metastasis,” the researchers explained, adding that prostasin has a known role in regulating these pathways.

That being said, they pointed out that prostasin may possibly mediate the process from hyperglycemia to cancer or may act as a marker for cancer susceptibility in those with elevated blood glucose.

“If a casual association were established in the future, prostasin may then be considered as a therapeutic target for treating both diabetes and cancer,” Gunnar’s group suggested.

There were a total of 4,658 individuals in this initial cross-sectional analysis, all of whom participated in the Malmö Diet and Cancer Study that kicked off in 1993. Among this group, 361 (7.75%) had prevalent diabetes. About 40% of the cohort was male and the average age was 58. After excluding those already with a diabetes diagnosis, 702 individuals developed diabetes during follow-up and 651 died from cancer.

Prostasin levels were measured from blood samples taken at baseline. For men, the highest quartile of prostasin was an average of 8.93 µg/mL and the lowest quartile was 7.97 µg/mL on average. For women, the highest quartile had an average level of 8.72 µg/mL and the lowest quartile was 7.62 µg/mL.

Diabetes diagnosis was defined as a fasting plasma glucose concentration of 126 mg/dL or higher on two separate tests plus a filled prescription for insulin or a glucose-lowering medication.

Models were adjusted for age, sex, waist circumference, smoking and drinking habits, LDL cholesterol, systolic blood pressure, and anti-hypertensive medication.