Diabetes-induced vascular calcification is associated with low pyrophosphate and its oral supplementation prevents calcification in diabetic mice.

Abstract

The predominant cause of death among diabetic patients comes from cardiovascular complications, including vascular calcification. The objectives of this study were to improve the understanding of the molecular mechanisms involved in diabetes-related calcification and to test potential preventive therapies. We found that levels of plasma pyrophosphate-a potent inhibitor of calcification-were decreased in type 1 and type 2 diabetic patients with cardiovascular symptoms. To further investigate vascular calcification, we developed a diabetic mouse model that showed increased aorta and renal calcification compared to control. Alkaline phosphatase activity was also increased in the circulation of diabetic mice, which resulted in a significant decrease in plasma pyrophosphate. Oral treatment with pyrophosphate prevented diabetes-induced calcification in mice, providing a direct translational value for clinical applications.