DS0404 - Innovation biomédicale

GLP-1 and angiogenesis : safety of T2 diabetes treatment ? – Angiosafe-T2D

Submission summary

Diabetic retinopathy (DR), that comprises Macular Oedema and Proliferative retinopathy is the most common microvascular complication of diabetes. Improved care reduced prevalence and incidence of retinopathy but DR remains a major problem because of the worldwide increase in diabetes. Evaluating the impact of new diabetic treatments on DR is therefore crucial. GLP-1 receptor agonists are introduced in the treatment of T2D and their efficacy is documented. Beside their therapeutic benefits, direct cardiovascular effects are also reported. T2D patients treated with GLP-1 analogs may suffer from microvascular complications such as macular oedema and DR, characterized by excessive retinal angiogenesis. Few studies have properly addressed the role of GLP-1-based therapies in regulating vascular integrity and angiogenesis. The role of GLP-1 on endothelial cell (EC) growth, EC integrity and angiogenesis thus needs to be characterized. Our aim is to provide the proof of concept that agonists of GLP-1 regulates angiogenesis and identifiy the underlying mechanisms. This project is also translational as among patients with DR, 5-10% have severe vision threatening DR including proliferative retinopathy and macular oedema. We will conduct analyses in 2 observational studies to investigate the possible link between incretin therapy and severe retinopathy in 2 clinical sites, at APHM, Marseille Nord and at the Centre Universitaire du Diabète et de ses Complications (CUDC) at Lariboisière Hospital, APHP, University Paris 7, 75010 Paris. A significant decrease in the prevalence of macular oedema and /or increase in the prevalence of proliferative retinopathy independently of HbA1c variation would be in favour of a ink between incretin therapy on diabetic retinopathy in humans.

Project coordination

Stéphane GERMAIN (Equipe "Rôle des protéines matricielles en hypoxie et angiogenèse")

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Centre interdisciplinaire de recherche en biologie (CIRB CNRS UMR7241-Inserm U1050) Equipe "Rôle des protéines matricielles en hypoxie et angiogenèse"
Centre de Recherche Des Cordeliers (UMRS 1138), PARIS Equipe "Pathogènèse du Diabète de Type-2:Aspects Cellulaires et Cliniques
Hopital Lariboisière (AP-HP) Centre Universitaire du Diabète et de ses Complications (CUDC),
AP-HM Marseille Pole ENdo , service d'endocrinologie et maladies métaboliques

Help of the ANR 275,020 euros
Beginning and duration of the scientific project: December 2014 - 36 Months

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