Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.
J Clin Endocrinol Metab
; 105(4)2020 04 01.
Article
en En
| MEDLINE
| ID: mdl-31589290
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Endoteliales
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Diabetes Mellitus Tipo 2
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Retinopatía Diabética
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Receptor del Péptido 1 Similar al Glucagón
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Exenatida
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Neovascularización Patológica
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia