Characterization of the expression of micro-RNAs in circulating extracellular vesicles from individuals with type 2 diabetes mellitus, retinopathy and cognitive impairment: search for potential biomarkers

• Grant number: 24/06699-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Lucia Cardillo Corrêa Giannella
• Grantee: Natália Emerim Lemos
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM), especially type 2 DM (T2D), is a highly prevalent condition; in 2021, the Surveillance of Risk or Protective Factors for Chronic Diseases by Telephone Survey in the State of São Paulo (Vigitel ESP) estimated the number of adult individuals with DM in this state at 3,178,067. The history of DM is marked by microvascular complications in those who cannot maintain good metabolic control, which is the majority. In Brazil, diabetic retinopathy (DR) is among the leading causes of acquired blindness, and cognitive impairment (CI), a complication that has been increasingly recognized as highly prevalent in T2D, has been little studied. In a recent meta-analysis, the presence of DR increased the risk of CI both in unadjusted analyses (by 2.7 times) and in analyses adjusted for other factors (by 2 times). The risk was detected in the presence of mild DR (2 times) and increased in the presence of moderate and severe DR (4 times). This proposal will be conducted on a series of individuals with T2D followed in primary care within the research project entitled "Cognitive decline in type 2 diabetes mellitus followed in primary health care: association with other complications and search for biomarkers for the construction of a prediction algorithm" and we expected to characterize, in individuals with T2D, the expression of micro-RNAs (miRs) in circulating extracellular vesicles (EVs) associated to the presence of DR and CI. To this end, the following objectives are being proposed: (1) to compare the miRs expression profile in EVs of individuals with T2D and the following combinations of complications: without DR and without CI, with DR and with CI, without DR and with CI and with DR and without CI; (2) to validate three differentially expressed miRs in a sample of 923 individuals with T2D, by real-time polymerase chain reaction (RT-qPCR). The expression values of these miRs in EVs will be analyzed, together with the status of each of the other complications and all clinical and laboratory data, using a machine learning approach, with the aim of identifying the characteristics associated to CI and DR and (3) to investigate the role of one of the differentially expressed miRs in endothelial dysfunction, using brain endothelial cells (HBECs) in experimental conditions that mimic a diabetic environment. Since EVs are considered important in intercellular communication, the study of miRs that are part of their composition can reveal mechanisms through DR and CI are interrelated. (AU)