Strategies for prevention and early intervention in type 1 diabetes mellitus

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease in which immune cells are manifesting an attack towards the insulin-producing β-cells of the pancreas, leading to β-cell loss and lifelong insulin dependence. The autoimmune reaction starts years in advance, before the onset of clinical symptoms. Today, this can be measured in the blood based on the presence of autoantibodies, providing an interesting ‘window of opportunity’ for screening, prevention and early T1D intervention.

T1D is divided in three stages of progression, depending on the strength of the autoimmune response (i.e. the presence of autoantibodies) and the level of glycemic control (i.e. reflecting β-cell function). The pre-symptomatic stages 1 and 2, characterized by the detection of two or more autoantibodies and normo- or dysglycemia, respectively, offer opportunities for screening and prevention. The European commission has therefore funded the EDENT1FI program (www.edent1fi.eu) to examine the feasibility and impact of population-wide screening and follow-up. Screening and monitoring of early-stage, pre-symptomatic T1D significantly reduces hospitalizations and life-threatening complications, e.g. diabetic ketoacidosis, while creating opportunities to participate in clinical intervention studies.

Multiple screening initiatives are arising worldwide, as the pharmaceutical industry pursues to develop interventions that slow down or prevent disease progression. In this regard, Teplizumab is a promising drug able to postpone T1D progression from stage 2 to symptomatic T1D (i.e. stage 3) by ~2-3 years. While this drug is FDA-approved for its use in the US in 2022, Europe is optimistically awaiting EMA-approval. When progressing to stage 3 T1D, characterized by typical clinical symptoms due to dysglycemia, research is focusing on modulating the autoimmune response and preserving the residual β-cell pool. In this way, every T1D stage offers its own opportunities to improve future T1D health care.