Given the dimensions that type 2 diabetes (T2DM) is acquiring in Spain, and its consequences, the early identification of people at risk of developing this disease is a priority, thus facilitating early management of symptoms. Research carried out within the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) has made it possible to advance this objective. This has been highlighted in the joint table that the Spanish Diabetes Society (SED) and CIBERDEM have been carried out within the framework of the XXXV Congress of the SED which is being held in Granada.
“This year the new biomarkers identified from the [email protected] study cohort were presented”
This has not been the only innovative contribution, coming from the area of basic and clinical research, that has been presented in this session. And, as he points out Eduard Montanya, scientific director of CIBERDEM, recent results of the diabetes research carried out by CIBERDEM have been known first-hand. “This year, the new biomarkers identified from the [email protected] study cohort, the functions of succinate in energy balance, glycemic control and circadian rhythms, and advances in gene therapy for diabetes and its transfer to the clinic.”
Risk biomarkers
In his conference, Eva Garcia EscobarCIBERDEM researcher at the University Hospital of Málaga, has recalled the epidemic proportions that DM2, the most common form of diabetes, is reaching worldwide. And it is that, “Despite improvements in treatments, T2DM represents a serious health problem with significant costs for health systems, so Early detection of subjects at risk, as well as early addressing of their symptoms, are essential to delay its appearance and prevent the development of future complications.”
The investigations carried out within the studio [email protected]a population-based prospective cohort trial with 7.5 years of monitoring carried out throughout the national territoryhave contributed to the identification of potential early biomarkers associated with the risk of onset of this disease and associated alterations in Spain (either indicating a higher or lower risk).
The research carried out within the [email protected] study has contributed to the identification of potential early biomarkers associated with the risk of the onset of this disease.
These include metabolomic profileswhich include the contribution of inflammatory processes and the role of muscle, and whey proteins (such as VEGFb or SP-D). They are also identified as possible indicators of the development of these metabolic pathologies. epigenetic (miRNAs), dietary, lifestyle factors or even, environmental (polluting particles). Specifically, regarding the nutritional pattern, as detailed by this expert, “it seems that a diet rich in vegetables and low in animal fats could not only reduce the risk of developing diabetes but it could also improve the regulation of glucose levels in stages prior to diabetes”.
These early indicators, in the opinion of the CIBERDEM researcher, “are useful in evaluating the risk of developing DM2 and open the possibility of new prevention strategies and as therapeutic targets”; However, as he acknowledges, “research aimed at their clinical and analytical validation is necessary before they can be used in clinical practice.”
Succinate
No less suggestive have been the novelties presented in this forum by Sonia Fernández Veledo, head of the DIAMET group of the Pere Virgili Health Research Institute (Tarragona) and CIBERDEM, showing the new functions of succinate discovered in energy balance, glycemic control and circadian rhythms.
He succinatea key component of the Krebs cycle, plays a essential role in mitochondrial energy production. In addition to its intracellular metabolic function, it can act as an extracellular signal through its specific hormone-like receptor SUCNR1, with autocrine, paracrine and endocrine effects. In the research released by researcher Sonia Fernández Veledo, the various roles of succinate (generated by both our cells and the intestinal microbiota) in the modulation of the inflammatory response and postprandial carbohydrate homeostasis have been evaluated.
Succinate, a key component of the Krebs cycle, plays an essential role in mitochondrial energy production
This is important, as he details, because “in various metabolic pathologies, such as obesity and diabetes, chronically elevated levels of succinate have been identified, which aggravates inflammation and alters its physiological functions in the regulation of energy homeostasis.” Indeed, activation of the succinate/SUCNR1 axis has been linked to the pathophysiology of diabetes and its associated complications. This research suggests, as this expert explains, that “succinate could be a biomarker with predictive capacity in this context.”
Despite the interest of pharmaceutical companies in inhibiting the succinate-SUCNR1 axis due to its relevance in metabolism, immunity and microbiome, approaches based on the use of SUCNR1 antagonists have not progressed. Starting from this reality, the proposal of this research group goes through “restore abnormal succinate levels to mitigate inflammation and restore physiological functions”explains Sonia Fernández Veledo. Therefore, succinate emerges as a fundamental metabolite in metabolic regulation, although its biology remains to be comprehensively understood.
Gene therapy
Regarding advances in gene therapy applied to diabetes, Fatima Boschfrom the Center for Animal Biotechnology and gene Therapy (CBATEG) from the Autonomous University of Barcelona, has shown research work carried out in animal models of type 1 and type 2 diabetes, with promising results.
“This gene therapy offers great translational potential in the fight against NASH, insulin resistance, type 2 diabetes, obesity and other related comorbidities“
Fatima Boschfrom the Center for Animal Biotechnology and gene Therapy (CBATEG)
“The better knowledge of the molecular mechanisms responsible for the development of these diseases, and the identification of key factors with anti-inflammatory and regenerative capacity, has been combined with important progress in the development of gene therapy, with efficient and safe vectors for gene transfer.” in vivo (such as AAV vectors) and to the improvement in the manufacturing of GMP vectors for the treatment of patients,” highlighted this UA expert.
In their research group they have made important progress in the development of gene therapy directly targeting the pancreas based on AAV to regenerate beta cell mass and its function in animal models of Diabetes type 1. Likewise, this congress has demonstrated the success achieved with AAV-FGF21 gene therapy to reverse metabolic alterations in dogs with type 2 diabetes; In fact, as he stated, “This gene therapy offers great translational potential in the fight against NASH, insulin resistance, type 2 diabetes, obesity and other related comorbidities”.