The pancreas in human type 1 diabetes

Abstract

Type 1 diabetes (T1D) is considered a disorder whose pathogenesis is autoimmune in origin, a notion drawn in large part from studies of human pancreata performed as far back as the 1960s. While studies of the genetics, epidemiology, and peripheral immunity in T1D have been subject to widespread analysis over the ensuing decades, efforts to understand the disorder through analysis of human pancreata have been far more limited. We have reviewed the published literature pertaining to the pathology of the human pancreas throughout all stages in the natural history of T1D. This effort uncovered a series of findings that challenge many dogmas ascribed to T1D and revealed data suggesting the marked heterogeneity in terms of its pathology. An improved understanding and appreciation for pancreatic pathology in T1D could lead to improved disease classification, an understanding of why the disorder occurs, and better therapies for disease prevention and management.

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

“…We found that SCT was associated with increased serum levels of IL-10, a regulatory cytokine, with decreased serum levels of IFN-g (T-helper 1 cytokine) and ATP production by CD4 + T cells (ImmuKnow), indicating reduced T-cell activation (24). Residual b-cell mass has been described in pancreatic specimens obtained from cadaveric donors with T1D, suggesting that interventions able to dampen inflammation may be beneficial toward achieving recovery of function (14). Whether SCT influence on T-cell and Treg function is one of the mechanisms involved in the current study remains controversial.…”

“…Increasing evidence supports the persistence of residual b-cell mass in pancreatic specimens obtained from patients with T1D and the persistence of C-peptide production years after diagnosis (14)(15)(16). These observations have important repercussions on the rationale for developing new interventions aimed at the recovery of function in patients with established diabetes.…”

Autoreactive T cells in type 1 diabetes

“…For decades, pathology studies relied on sporadic access to T1D pancreata (11). Early efforts to recover T1D pancreata include collecting autopsy specimens from recently diagnosed patients in the United Kingdom (12) and limited percutaneous biopsies from living patients in Japan (13).…”

The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

“…In most individuals with autoimmune type 1 diabetes, beta cell destruction is a chronically progressive and very slow process that starts long before overt disease. During this "silent" phase, autoantibodies are produced and self-reactive activated lymphocytes infiltrate the islets of Langerhans (Rowe et al, 2011). Autoantibodies that target self-antigens in the insulin-secreting beta cells of the pancreas include: islet cell autoantibodies (ICA), insulinoma-associated antigen-2 antibodies (IA-2A), antibodies against the related antigen IA-2 beta (IA-2), insulin autoantibodies (IAA), autoantibodies to the 65kDa isoform of glutamic acid decarboxylase 65 (GADA), and the recently identified autoantibodies to the zinc transporter 8 (ZnT8A) ( Table 2).…”

“…promoting insulitis in susceptible individuals (Rowe et al, 2011). In a genome-wide association study, 41 distinct genomic locations provided evidence for association with type 1 diabetes in the meta-analysis (Barrett et al, 2009).…”