Aproximació multifactorial al procés de l'arteriosclerosi en la diabetis mellitus tipus 2: Estudi conjunt de factors genètics protrombòtics (polimorfismes de les glicoproteïnes plaquetàries), factors d'inflamació, factors de la matriu extracel·lular (metaloproteïnasa PAPP-A) i valoració de la utilitat de la pulsioximetria en el cribatge de l'aterosclerosi subclínica

Abstract

The increased prevalence of cardiovascular events in type 2 diabetes is not fully explained by an excess of the conventional risk factors for atherosclerosis and this has led to research into new pathophysiological aspects of the development of atherosclerotic lesions over time. There is increasing evidence that atherosclerosis in type 2 diabetes is the result of the interaction between metabolic factors (chronic inflammatory and insulin resistant states, β cell dysfunction) and disorders of haemostasis (endothelial dysfunction, prothrombotic state). The papers included in this Thesis try to research into atherosclerosis in DM2 studying: 1) a serum biomarker: the PAPP-A (Pregnancy Associated Plasma Protein); 2) a genetic factor: polymorphisms of platelet glycoprotein (GP) Ib (VNTR), Ia / IIa (807 C/T), IIb / IIIa (PlA1/A2); 3) a clinical factor: pulse oximetry as screening method of subclinical carotid atherosclerosis. Thesis results suggest: 1a) type 2 diabetic patients may have altered the repaired mechanism of IGF-1/PAPP-A axis in atheroma plaque in relation to glycemic control and independently of other metabolic factors; 1b) serum PAPP-A and IGF1 do not appear to be useful serum biomarkers for carotid atherosclerosis in type 2 diabetic patients with stable glycemic control; 2a) the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes; 3) pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM.

Date of Award	8 Jul 2010
Original language	Undefined/Unknown
Supervisor	Anna Maria Sanmartí Sala (Director) & Jorge Luis Reverter Calatayud (Director)