Role of Circulating Pyrophosphate as a Biomarker of Mediacalcinosis in Type 2 Diabetic Patients
Type 2 diabetes currently affects around 4 million people in France, with the number of cases rising steadily. Complications of T2DM are essentially cardiovascular. In particular, T2DM is associated with calcification of peripheral vessel walls (mediacalcosis), responsible for increased vascular stiffness. This calcium deposition is known to be a cardiovascular risk factor, but the mechanism of its deposition in relation to diabetes is not clearly established. An important blood compound, inorganic pyrophosphate (PPi), which is the body's natural anti-calcifier is impacted in some way in T2DM. PPi is degraded by alkaline phosphatase (ALP), and is produced by an enzyme called ENPP1. ENPP1 activity is decreased and APL activity increased in insulin-resistant subjects, which could contribute to a decrease in tissue and circulating PPi, and thus favor a tissue pro-calcifying balance. We propose to test this hypothesis in a pilot study characterizing plasma PPi levels, in relation to ENPP1 activity, in type 2 diabetic patients. The aim of the study is also to determine if there is a link between blood PPi levels and the progression of calcifications in arteries.
• Adult men (between 40 and 70 years of age).
• T2DM defined according to ADA or HAS criteria, evolving for more than 6 months, may be : - Not complicated
‣ Complicated by diabetic retinopathy and/or diabetic nephropathy (creatinine clearance \> 60 ml/min) and/or peripheral arterial disease and/or ischemic heart disease and/or stroke. - With dyslipidemia (LDLc \> 1.90) and/or a history of past or active smoking.
⁃ Balanced with HbA1c \< 8% according to patient's personalized objectives, or unbalanced with HbA1c \> 9%.
⁃ Treated with insulin therapy (single or multi-injections) or not. - Whose treatment includes at least one iSGLT2.
• Member of 'Sécurité Sociale