Characterization of extracellular vesicles isolated from saliva of individuals with diabetes mellitus secondary to pancreatic ductal adenocarcinoma and type 2 diabetes mellitus

• Grant number: 23/17919-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luiz Henrique Gomes Matheus
• Grantee: Anita Andrade Reis
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pancreatic ductal adenocarcinoma (ACDP) is a neoplasm with a very unfavorable prognosis, the diagnosis of which is mostly made in the presence of locally advanced or metastatic disease, a stage in which surgical therapeutic approach is no longer indicated. From a clinical point of view, recent-onset diabetes mellitus (DM) is considered a paraneoplastic manifestation of ACDP, and may be a marker for early diagnosis of the neoplasm, as it appears two to three years before the diagnosis of the tumor in 80 % of patients. Thus, the clinical suspicion that the etiology of new-onset DM is not common forms of DM, such as type 2 DM (DM2), but rather DM secondary to ACDP, has important clinical implications, as it may allow the diagnosis of the tumor in a still resectable phase, increasing the chances of cure. In a previous study by the team involved in this project, we validated the differential expression of three serum microRNAs (miRs) that had been described as capable of differentiating DM secondary to ACDP from DM2 and identified some messenger RNAs (mRNAs) differentially expressed in extracellular vesicles (EVs)) circulating in individuals with these two forms of DM. The present project aims to standardize the isolation and characterize EVs isolated from saliva samples from individuals diagnosed with ACDP and recent-onset DM, comparing them with those isolated from individuals with DM2. To this end, 15 individuals with ACDP and recent DM diagnosis (< 3 years) and 15 with long-standing DM2 (> 3 years) will be included, matched as much as possible for age, sex and glycated hemoglobin values, using EV characterization methodologies already standardized by the team.