Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association

Abstract

Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.

HLA-A*24Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft

“…The current results indicate that similar to observations in pre-type 1 diabetes, the presence of HLA-A*24 or autoantibody surges predicts b-cell loss during an inflammatory and/or immune process in islet allograft recipients (7,8). The association of early autoantibody rises with poor graft outcome confirms previous observations and has been explained as the consequence of autoantigen release after b-cell death (12).…”

“…However, a positive outcome can be counteracted by other factors, including preexisting autoreactive T cells, HLA alloantibodies, or high lymphocyte counts (2-4). In recipients of a sufficiently large intraportal islet allograft (5,6), we investigated whether the presence of HLA-A*24, HLA-DQ2/DQ8, or rising islet autoantibody levels, previously shown to independently predict rapid b-cell loss in prediabetes (7,8), associates with poor functional graft outcome. …”

2. Classification and Diagnosis of Diabetes

“…Patients with type 1 diabetes often present with acute symptoms of diabetes and markedly elevated blood glucose levels, and approximately one-third are diagnosed with life-threatening ketoacidosis (2). Several studies indicate that measuring islet autoantibodies in relatives of those with type 1 diabetes may identify individuals who are at risk for developing type 1 diabetes (17). Such testing, coupled with education about diabetes symptoms and close follow-up in an observational clinical study, may enable earlier identification of type 1 diabetes onset (18).…”

Peptide serum markers in islet autoantibody-positive children

“…The development of type 1 diabetes includes an asymptomatic period of autoimmunity identified by the presence of islet autoantibodies, with subsequent progression to dysglycaemia and clinical diabetes [1]. While the development of islet autoantibodies is most prominent around 1-2 years of age [2][3][4], the incidence of clinical diabetes appears to be relatively constant in multiple islet autoantibody-positive children and adolescents [5].…”