Our group, since its formation eight years ago, has focused its research on the role of Maillard reaction on the development of chronic diabetes complications, specially on the physiopathologic mechanisms underliyng vascular disease.

On several series, diabetes prevalence has been estimated on 1%-5% of the World population. People with this condition are somehow susceptible to develop microvascular pathology, whose clearer clinical manifestations are observed on retina and glomeruli. This people also suffer from an increased frequence of atheromatosis on their vessels. By all these considerations, diabetic condition is among the risk factors of cardiovascular disease.

Our group explores one of the explanative hypotheses about these complications. Considering sustained hyperglucaemia the major factor responsible for diabetes complications, this hyperglucaemia should actuate through metabolic and/or biochemical alterations, both at the extra or intracellular level, thus originating structural and functional alterations. In this context, Maillard reaction hypotheses purposes that the formation and accumulation of heterogenous nonenzymatic modifications, apparently irreversible, of amino group bearing biomolecules, such as proteins, certain phospholipid and potentially nucleic acids,( agrupated into the term of AGE products (advanced glycation end products)), contributes to diabetes chronic complications pathogenesis.

In this sense, in our first group, we observed that glycation levels (glycation:nonenzymatic attachment of glucose to proteins, in contrast with N-glycosilation or O-glycosilation, which are enzyme mediated glicid transference) is a good indicator of cholesterol levels change, and that glycation process affects not only plasma cholesterol levels of diabetes patients, but also in non diabetic people (Prat, 1989a; 1989b). The glycation would affect lipid metabolism throughout the apolipoprotein modification, which leads to changes in their catabolism, thus contributing, at least partially, to the lipid alterations present in diabetes. These alterations on lipoprotein profile, specially on LDL (Low-density-lipoproteins), have been implied in the atheromatoses development (Prat, 1991). By these data, and, of course, the preeminent investigations of other groups, Maillard reaction was implied in atheromatoses development in a multifactorial fashion, by lipoprotein modification, vascular extracellular matrix alterations, and disturbances on arterial intimal homeostasis, and we proposed the Glycation hypotheses of arteriosclerosis (Pamplona, 1993). In another side of diabetic dislipaemia, we have also obtained data on fatty acid profile changes on several lipoprotein and cell membranes, attributable to changes in desaturase activties and oxidative damage on them (Pamplona, 1994). Our last research in this field, in collaboration with Dr. J.R. Requena, Prof S.R. Thorpe, and J.W. Baynes, at South Carolina University has constiued the first chemical evidence for Maillard reaction on aminophospholipids, finding increased levels of this modification in diabetes (Pamplona, 1995).

To explore other aspects of Maillard reaction, implied on extracellular matrix homeostasis, our group has studied collagen changes associated with the advanced stage of Maillard reaction (Bellmunt, 1995a), throughout physico-chemical properties associated with the presence of a characterized AGE product, as pentosidine (Bellmunt, 1995b). Recently, in collaboration with the group of Prof. V.M. Monnier (Institute of Pathology, CWRU), we have been able to establish chemical evidence for the in vivo presence of other of these advanced Maillard reaction products, pyrraline (Portero-Otín, 1995), and the possible pathways of protein modification by this product (Nagaraj, 1996). We have been also able to prove that pyrraline is excreted by urine (Portero-Otín, 1997), and the relationship of its elimination with metabolic control of diabetic patients (Portero-Otín, in preparation).