GLP-1 analogue and vitamin D associated to intensive insulin therapy to preserve residual beta cell function in type 1 diabetes patients after five years of clinical disease

• Grant number: 13/25506-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2014
• End date: May 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sergio Atala Dib
• Grantee: Monica Andrade Lima Gabbay
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Type 1 diabetes (T1D) is the result of an immunological desbalance leading to beta cell destruction by activated autoreactive T cells and their cytokines. Although until now, there are no effective therapy direct to diabetic pathogenesis that prevents the disease, much has been done aimed at terciary prevention, i.e, intervention at ongoing immunological process to preserve beta cell mass and reduce clinical manifestation and the disease progress.Recently, it was demonstrated that patients who's once believed do not have endogenous insulin reserve, have detectable C peptide using ultrasensitive assay. Those patients, generally excluded from the prevention trials, may benefit from intervention to preserve beta cell function or to prevent complications.Our aim was study T1D with less than 5 years of clinical disease using an ultrasensitive assay of C peptide to assess residual beta cell function and evaluate the effects of vitamin D (might favor a more benign immunological profile), Liraglutide (might favor beta cells expansion and resistance to apoptosis) or both associated to intensive insulin therapy association over C peptide and cellular and humoral immunological behavior. Two hundred patients (10 to 30 years old) will be submitted to mixed meal tolerance test for C peptide evaluation and 100 with positive C peptide will be selected. Those patients will be subdivided in 4 groups:only vitamin D, only liraglutide,both medications, without medication and 25 patients with negative C peptide will represent control group. At 0, 3 , 6 months for C peptide, inflammatory cytokines (IL-6, TNFa, IL-17), anti-inflammatory cytokines (IL-4, IL-10 e TGF²), chemokines, Treg cels (CD127, CD45, FoxP3) and antipancreatic antibodies (GAD65, IA2, ZnT8) will be evaluated. (AU)