Bénédicte Gaborit 1,2 , Jean-Baptiste Julla 3,4 , Samaher Besbes 5 , Matthieu Proust 5 , Clara Vincentelli 1,2 , Benjamin Alos 5 , Patricia Ancel 1 , Fawaz Alzaid 4 , Rodrigue Garcia 5 , Philippe Mailly 5 , Florence Sabatier 1 , Maud Righini 6 , Pierre Gascon 6,7 , Frédéric Matonti 6,7 , Marie Houssays 8 , Louisa Goumidi 1 , Lucile Vignaud 9 , Xavier Guillonneau 9 , Ali Erginay 10 , Bénédicte Dupas 10 , Jennifer Marie-Louise 10 , Marianne Autié 10 , Tiphaine Vidal-Trecan 3 , Jean-Pierre Riveline 3,4 , Nicolas Venteclef 4 , Pascale Massin 10 , Laurent Muller 5 , Anne Dutour 1,2 , Jean-François Gautier 3,4 , Stéphane Germain 5 Show Affiliations »
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AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA ) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs .We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR . In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR , while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells , no effect on total length and number of capillaries . Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization . CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR . © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
RCT Entities: Population
Interventions
Outcomes
AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR ). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans . In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR , as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia -induced neovascularization of the retina in mice . RESULTS: In the cohort of 3154 T2D patients , 10% displayed severe DR . In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR , while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR . © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Disease
Gene
Species
Keywords:
angiogenesis; angiosafe Type 2 diabetes study; fundus photography; glucagon like peptide 1 receptor agonist; retinopathy; type 2 diabetes
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Year: 2020
PMID： 31589290 DOI： 10.1210/clinem/dgz069
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958