Effects of Fenofibrate on Endothelial Progenitor Cells in Diabetes

Effects of Fenofibrate on Endothelial Progenitor Cell Levels in Diabetic Patients With Retinopathy. A Randomized Controlled Trial.

Long-standing diabetes is often complicated by retinopathy. The mechanisms that induce the development of diabetic retinopathy are incompletely understood and include alterations in bone marrow derived vasculogenic cells called "endothelial progenitor cells". Fenofibrate is a PPAR-alpha agonist used for the treatment of mixed dislipidemia and hypertriglyceridemia. In a trial conducted in type 2 diabetic patients, the drug fenofibrate has reduced retinopathy-related endpoints suggesting a direct effect of the drug on the mechanisms that drive the development of this complication. Herein, the investigators hypothesize that fenofibrate treatment can increase circulating EPC levels in diabetic patients with retinopathy, compared to placebo.

Long-standing diabetes is often complicated by retinopathy. The mechanisms that induce the development of diabetic retinopathy are incompletely understood and include alterations in bone marrow derived vasculogenic cells called "endothelial progenitor cells". Fenofibrate is a PPAR-alpha agonist used for the treatment of mixed dislipidemia and hypertriglyceridemia. In addition to lowering triglyceride-rich lipoproteins, PPAR-alpha agonism with fenofibrate has several additional molecular benefit on the vessel wall, such as reduction of inflammation. In a trial conducted in type 2 diabetic patients, the drug fenofibrate has reduced retinopathy-related endpoints suggesting a direct effect of the drug on the mechanisms that drive the development of this complication. Preliminary data of ours on the effects of fenofibrate on cultured EPC show that this drug has the potential to improve EPC and, consequently, may benefit patients with retinopathy. Herein, the investigators hypothesize that fenofibrate treatment can increase circulating EPC levels in diabetic patients with retinopathy, compared to placebo.

Change in endothelial progenitor cell (EPC) levels in fenofibrate-treated vs placebo-treated patients over 12 weeks.

Change in circulating progenitor cell (CPC) levels in fenofibrate-treated vs placebo-treated patients over 12 weeks.

Inclusion Criteria: Type 1 or type 2 diabetes Diabetic retinopathy Age 18-70 Both sexes Exclusion Criteria: Age <18 or >70 at enrollment Hereditary muscle disorders Uncontrolled hypothyroidism Elevated alcohol consumption Renal failure Hepatic failure Allergy to fenofibrate or excipients Acute / chronic pancreatitis Pregnancy and lactation.

Bonora BM, Albiero M, Morieri ML, Cappellari R, Amendolagine FI, Mazzucato M, Zambon A, Iori E, Avogaro A, Fadini GP. Fenofibrate increases circulating haematopoietic stem cells in people with diabetic retinopathy: a randomised, placebo-controlled trial. Diabetologia. 2021 Oct;64(10):2334-2344. doi: 10.1007/s00125-021-05532-1. Epub 2021 Aug 9.