Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell Transplantation and Conventional Medical Therapy.

Jaquellyne G Penaforte-Saboia,Ana Paula D R Montenegro,Belinda P Simões,Maria Carolina Oliveira,Hussain Akhtar,Renan M Montenegro,Daniela Aparecida Moraes,Carlos E Couri,Marilia Brito Gomes,Juliana B E Dias,Kelen Cristina Ribeiro Malmegrim,Carlos A Negrato,Virginia O Fernandes,Livia A Batista

doi:10.3389/fendo.2017.00331

Abstract

To explore the impact on microvascular complications, long-term preservation of residual B-cell function and glycemic control of patients with type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) compared with conventional medical therapy (CT). Cross-sectional data of patients treated with AHST were compared with patients who received conventional therapy from the Brazilian Type 1 Diabetes Study Group, the largest multicenter observational study in type 1 diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on average. An assessment comparison was made on the presence of microvascular complications, residual function of B cell, A1c, and insulin dose of the patients. After a median of 8 years of diagnosis, none of the AHST-treated patients (n = 24) developed microvascular complications, while 21.5% (31/144) had at least one (p < 0.005) complication in the CT group (n = 144). Furthermore, no case of nephropathy was reported in the AHST group, while 13.8% of CT group (p < 0.005) developed nephropathy during the same period. With regard of residual B-cell function, the percentage of individuals with predicted higher C-peptide levels (IDAA1C ≤ 9) was about 10-fold higher in the AHST group compared with CT (75 vs. 8.3%) (p < 0.001) group. Among AHST patients, 54.1% (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT (p < 0.001) group. Patients with newly diagnosed type 1 diabetes treated with AHST presented lower prevalence of microvascular complications, higher residual B-cell function, and better glycemic control compared with the CT group.

Highlights

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from autoreactive CD4+ and CD8+ lymphocytes attack against pancreatic beta cells [1], leading to symptomatic diabetes and lifelong insulin dependence [2]
Data of 24 subjects from autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) were contrasted against the data of 144 subjects from the conventional medical therapy (CT) (70% males in both, p = 0.945)
Trials analyzing the effects of AHST in new-onset t1dm have shown promise in significantly attenuating the loss of insulin secretion [8, 9, 19, 20]

Summary

Introduction

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from autoreactive CD4+ and CD8+ lymphocytes attack against pancreatic beta cells [1], leading to symptomatic diabetes and lifelong insulin dependence [2]. Immunotherapy aims to preserve the remaining mass of B cells by attenuation of the activated, autoreactive T cells [4]. Bone marrow transplantation (BMT) has been studied as a therapeutic approach for T1DM since the 1980s [5]. Studies suggested that allogeneic BMT primarily for hematological disease could potentially transfer T1DM and in some instances, BMT could reverse it [6]. It was demonstrated that immunological intervention in newly diagnosed type 1 diabetic patients resulted in a slower decline of beta-cell function [7]

Methods

Results

Conclusion