10% of the polymorphisms associated with type 1 diabetes are located in long non-coding RNAs (lncRNAs), that is, what was until now considered ‘junk DNA’. Basic research work carried out in Spain is helping not only to better characterize the function of these lncRNAs, but suggest the possibility that these molecules play an essential role in the appearance and development (pathogenesis) of type 1 diabetes. This opens a new avenue of research for the development of future therapies.
This is how Dr. Izortze Santín Gómez, professor at the University of the Basque Country and researcher at the Biocruces Bizkaia Research Institute (Bilbao), who at the XXX National Congress of the Spanish Diabetes Society has shown his most recent studies on the involvement of lncRNAs in the destruction of the pancreatic beta cell in DM1.
Although the non-coding genome was once thought to be junk and useless, non-coding RNAs are now known to play a crucial role in regulating multiple processes, such as gene expression. In the studies carried out by Dr. Santín, it has been observed that “some long non-coding RNAs that contain polymorphisms associated with type 1 diabetes regulate very important intracellular pathways in the pathogenesis of this disease, such as inflammation or death of the beta cell pancreatic ”.
Based on these findings, and thanks to the work of functional characterization of the lncRNAs associated with type 1 diabetes, “it seems logical to think that these molecules are fundamental in the pathogenesis of the disease“Says the expert from the Biocruces Research Institute. According to Dr. Santín speculates, “the characterization of its function at the pancreatic beta cell level will help to clarify the genetic-molecular mechanisms by which the pancreatic beta cell is destroyed in type 1 diabetes and will provide the necessary information for the development of therapies based on the modification of these lncRNAs ”.
All in all, it is assumed that very little is yet known about the role of these lncRNAs in beta cell destruction. For this reason, Dr. Izortze Santín insists, “the first thing would be to characterize their function, and then proceed to design strategies that allow modifying the harmful impact of these lncRNAs associated with type 1 diabetes on the viability of the pancreatic beta cell.”
Hidden cardiovascular risk in diabetes
Another topic discussed at the SED-CIBERDEM joint table held at this Congress has focused on uncovering the impact of hidden cardiovascular risk in the patient with diabetes, that is, the residual risk that persists when all those risk factors have been modified considered important. The problem is important, since up to a third of patients apparently free of cardiovascular danger end up having a heart attack.
A clear example of this situation is cholesterol, according to Prof. Josep Ribalta, from the Rovira i Virgili University of Reus (Tarragona). Having high cholesterol levels is one of the main risk factors for having a heart attack; Nevertheless, “more than 30% of heart attacks occur in people with apparently normal LDL cholesterol”, Points out this expert. This normality is based on findings derived from routine analytics, but with the use of more specialized analytical tools, it can be perceived, for example, that LDL particles are more numerous and smaller, that their HDLs work less effectively and / or that there are some lipoproteins (remnants) that the body has trouble eliminating.
Therefore, Prof. Ribalta proposes two lines of work to help clinicians identify these risky situations beyond routine testing. On one side, recommends the use of methodologies such as nuclear magnetic resonance that make these characteristics visible, being necessary that they have a routine application in the clinic in the not too distant future; In his opinion, “nuclear magnetic resonance is a useful tool to detect diabetic dyslipidemia in a precise way, and with possibilities of being applied to the clinic.”
For other, this expert recommends exhaustively analyzing other properties of lipoproteins (not just his concentration) that make them at normal concentrations more likely to deposit in the arteries. Thus, it is suggested that it can be very informative to study its electrical charge, the post-translational modifications of some of its proteins or the bacterial wall debris that they carry once they are produced in the intestine.
In short, as Josep Ribalta summarizes, “if we are able to identify the (hidden) parameters that reveal this risk and if we improve our knowledge of what causes them and how to modify them, we will be taking important steps to prevent the consequences of hidden cardiovascular risk in people with diabetes” As an example, the professor at the Rovira i Virgili University indicates that the presence of small LDL depends largely on triglycerides and, therefore, in certain patients, the control of triglycerides may be more important than that of cholesterol.