Page 16 - CIBERDEM-2015-eng

Scientific Programmes
In 2015, the groups forming the programmes were provided with financing from the ISCIII, from the Ministry of the Economy and Competitiveness, as well as from private institutions (European Foundation for the Study of Diabetes, Marató on TV3, CaixaImpulse, FIV Recoletos, etc.). The most relevant scientific milestones reached by the Programmes during 2015 are listed below, arranged on the basis of the main objectives of each Pro- gramme:
PROGRAMME 1. Epidemiology, genetics and epigenetics of diabetes mellitus. Chronic complications and comorbidities.
1. Epidemiology of diabetes mellitus, its chronic complications and comorbidities
In 2015 the field work for the [email protected] study was organised and got under way and will determine the incidence of diabetes and associated metabolic diseases in Spain. As regards the Segovia study, a prospective investigation was carried out in which a total mortality of 7.4 % was determined, the main causes being cancer (49%) and cardiovascular events (21.6%), and the ictus being the most com- monly registered cardiovascular event (24.83%). An epidemiology study has also been carried out which has revealed that the Adenine-Adenine (AA) genotype of the SNP-rs4730153 of the visfatin gene protects against cardiovascular disease in subjects with/without obesity.
2. Genetics, epigenetics and environmental factors involved in the development of diabetes and its complications
With regard to disorders in lipid metabolism, an NMR method has been developed to evaluate the lipoprotein profile in diabetic patients. Evidence has furthermore been given that the circulating levels of proteins FABP4 and FABP5 are not genetically determined and are associated with atherogenic dyslipidemia (Ibarretxe D, Nutr Metab Cardiovasc Dis. 2015). It has also been identified that circulating PCSK9 is increased and associated with atherogen- ic dyslipidemia in diabetic patients. The adminis- tration of mimetic peptides of the major protein of HDLs (apolipoprotein A-I) has been observed to sig- nificantly delay tumour growth in a murine model of inherited breast cancer.
3. Molecular mechanisms associated with the appearance and progression of chronic complications of diabetes: therapeutic strategies.
A new score for cardiovascular risk in the diabetic population has been defined. In connection with the study of vascular complications of diabetes, opti- mised peptides are being used to enter cells to in- hibit two key pathways, the nuclear factor Kappa B (NF-KB) and that of the JAK/ STAT pathway. These peptides, in both in vitro and in vivo studies, have shown to be potent anti-inflammatory and anti-fi- brotic agents. The studies carried out with a mimetic peptide of SOCS (Suppressors of Cytokine Signalling) are protected by a patent in the area of retinopathy, nephropathy and vascular affectation of diabetes (Recio C, Basic Res Cardiol. 2015).
Diabetes is a risk factor in Alzheimer Disease (AD). The usefulness of studying the neurodegeneration of the retina for predicting the risk of developing AD has been assessed. In preclinical studies of diabet- ic retinopathy (Simó and Hernández, Prog Retin Eye Res 2015) an animal model has been characterised (db/db mouse) which recapitulates the development of diabetic retinopathy in humans. This is a useful model for further studing the mechanisms leading to the diabetes-induced neurodegeneration of the retina and for testing neuroprotective drugs, with the effectiveness of GLP-1 administered in collyrium for preventing neurodegeneration and the first microvas- cular lesions being noteworthy (Hernández C, Diabe- tes 2015). The inhibition of phosphatase 1B proteins in photoreceptors and in retina explants has been shown to give protection against the action of proin- flammatory cytokines in such a way as to keep the IGF-IR-mediated survival signalling active, reducing reactive gliosis. This work identifies a new therapeu- tic target against neuroinflammation which occurs in early phases of diabetic retinopathy (Arroba and Val- verde, Invest Opthalmol Vis Sci 2015).
16 I Annual report 2015 I CIBERDEM