HDL lipoprotein functionality and regulatory gene expression after treatment with DPP-4 enzyme inhibitors and NPH insulin in Type 2 Diabetes

• Grant number: 22/16441-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Elizabeth Rossi da Silva
• Grantee: Maria Elizabeth Rossi da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Aritania Sousa Santos ; Maria Lucia Cardillo Corrêa Giannella ; Marisa Passarelli

Abstract

Insulin secretion and actions are reduced at the diagnosis of T2D and continue to decline with the progression of the disease, despite which treatment was instituted. This progression towards the inclusion of new therapies suggests that they do not correct all the metabolic and hormonal dysfunctions necessary to prevent beta cell failure. In a previous study (FAPESP- 2009 / 13904-0), we evaluated the introduction of sitagliptin (DPP-4 enzyme inhibitor) or bedtime NPH insulin as complementary therapies in T2D patients treated with oral hypoglycemic agents and inadequate glycemic control. The results obtained (improvement in glycemic control after 6 and 12 months) were not attributed to permanent improvement in alpha or beta cell function, body weight loss or reduction in serum lipotoxicity, suggesting the need for more comprehensive information than biochemical and hormonal determinations used. These do not discriminate the functionality of lipoproteins or factors interfering with insulin secretion and action (microRNAs) that may have been altered by medications. In order to continue the evaluation of the effects of sitagliptin and bedtime NPH insulin in patients with DM2, we intend to: 1-Identify the influence of treatments on the serum levels of miRNAs related to the function of pancreatic alpha and beta cells and analyze their biological role - target genes involved in secretion of pancreatic hormones and resistance to insulin action; 2- Asses the ability of HDL particles to remove cellular cholesterol, which is implicated in the complications of DM and beta cell function. The integrated analysis of these data may contribute to the understanding of the pathophysiology of DM, new therapeutic targets not covered by treatments or personalized therapy. (AU)