RESUMO
BACKGROUND: Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. METHODS: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. RESULTS: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. CONCLUSION: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control. TRIAL REGISTRATION: 37001514.0.0000.5257.
RESUMO
ABSTRACT Objective: The aim of the study was to assess the autoimmunity in first degrees relatives (FDR) of patients with type 1 diabetes (T1DM) and the progression to T1DM after 10 years of follow up in the Brazilian population. Subjects and methods: Non-diabetic FDR of T1DM patients were interviewed and blood was drawn for autoantibodies measurement (GADA, IA-2A, IAA, ZnT8A). Serum samples were analyzed by standard radioligand binding assays performed at the Federal University of Rio de Janeiro (GADA, IAA and IA2A), and at the Skäne University Hospital, Sweden (ZnT8A). The FDR were interviewed by phone after 10 years to determine if they had developed T1DM. Descriptive statistical analysis was performed and results were described as means and standard deviation (SD). Results: 81 individuals were analyzed. Thirteen subjects had positive autoantibodies associated with T1DM.10 were positive for 1 autoantibody and 3 subjects were positive for multiple autoantibodies (1 of them showed positivity for 2 autoantibodies - GADA, ZnT8A - and the other two were positive for 3 autoantibodies - GADA, IA2A, ZnT8A). The 3 subjects with multiple positive autoantibodies developed T1DM within 10 years. Conclusions: In Brazilian FDR of T1DM patients, the positivity for multiple autoantibodies indicate a greater chance of progression to T1DM, similar to observed in Caucasians. ZnT8A was helpful in the risk assessment for T1DM development.