Preventing excessive platelet production in diabetics

Researchers have uncovered a novel mechanism behind excessive platelet production present in people with diabetes, placing them at increased risk of cardiovascular complications such as heart attack and stroke. The research is welcome news for the 1.7 million Australians with diabetes, 70% of whom are likely to experience some form of cardiovascular disease.

Platelets play an integral role in cardiovascular disease, not only in the formation of the blood clots responsible for heart attacks and stroke, but also in the progressive development of the disease. Patients with diabetes have increased numbers and reactivity of platelets, which contribute to their increased risk of cardiovascular complications. Furthermore, current anti-platelet therapies prescribed to patients at high risk of cardiovascular disease, such as aspirin, have been shown to be less effective in patients with diabetes.

The research team, co-led by Associate Professor Andrew Murphy from Melbourne’s Baker Heart and Diabetes Institute, used a mouse model of diabetes to demonstrate that high blood glucose is responsible for the increased production of platelets and the subsequent acceleration of cardiovascular disease in diabetes. Using the glucose-lowering drug dapagliflozin — one of a new class of drugs recently introduced as a therapy for type 2 diabetes — the researchers were able to normalise levels of platelet production.

While these studies were able to completely control blood glucose levels, this is not the case in people on this drug, suggesting a second or complementary approach is required. However, Associate Professor Murphy said the group has identified the exact protein, S100A8/A9, involved in triggering this platelet response to high blood glucose.

“We then found that a specific inhibitor of the protein, ABR-21575 (paquinimod), currently approved as an orphan drug for systemic sclerosis, was able to prevent the exacerbated platelet production, curbing the development of cardiovascular disease,” he said. “With the drug already approved for another indication, it could mean a quicker route to market for use in the setting of diabetes.”

The team has identified increased platelet numbers and higher levels of S100A8/A9 in a group of patients with type 2 diabetes. They have also demonstrated a correlation between high blood glucose levels and newly formed platelets, indicating increased platelet production in these patients. It is hoped that their research, published in the Journal of Clinical Investigation, could one day lead to a suitable anti-platelet therapy for the treatment of cardiovascular disease.

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