A molecule known as pre-kallikrein (PK) is a risk factor for the vascular complications associated with type 1 diabetes, according to new research.
The study, conducted by researchers at the Medical University of South Carolina (MUSC), the American University of Beirut (AUB) and Case Western Reserve University, suggests that high levels of PK is a risk factor diabetic vascular disease throughout the body, not just in the kidneys, as previously thought.
What is pre-kallikrei, and how is it associated with diabetic vascular disease?
PK is found in the walls of blood vessels. Normally, it reaches the surface of the vessel, then activates a number of molecular signals. These signals then cause changes in dilation and tension.
However, when things go wrong with blood vessels in people with diabetes, PK comes into direct contact with the cells of the inner vessel layers, known as the intima-media. By coming into contact in this way, the circuit of an alternative pathway of chronic inflammation becomes closed, and it is this inflammation that is believed to cause the blood vessel thickening associated with diabetic kidney disease and retinopathy.
To find out, the researchers examined patient samples stored at MUSC. They looked at levels of PK in blood samples and used ultrasounds to measure the thickness of the intima-media in the carotid arteries. The researchers discovered a significant link between levels of PK and thickness of the intima-media.
A promising study, but no causal link found between PK and thicker arteries
However, the study does not prove that one factor causes the other. Perhaps high levels of PK cause thicker arteries, but it could also be that thicker arteries cause higher levels of PK. However, this marks a significant first step in the prevention of vascular complications in people with type 1 diabetes. Next, the researchers hope to develop drugs that will be able to target PK in preclinical studies.
“These preclinical studies not only will give us insights into the involvement of plasma PK in vascular disease, but will also contribute to development of novel treatment strategies for diabetic vascular disease,” said Ayad A. Jaffa, who led the study.
The findings are published in the journal Diabetes.

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