Arresting type 1 diabetes: are we there yet? Obstacles and opportunities

Abstract

More than 100 years after the discovery of insulin, the exact etiology and pathophysiology of type 1 diabetes (T1D) remains elusive, but our knowledge is growing. This leads to louder calls to initiate a risk screening for T1D in the general population. This risk screening could be based on the genetic risk (in the general population or targeted HLA genotyping in family members of persons with T1D) or on the screening for autoantibodies in blood (e.g., antibodies against insulin, GAD, IA2, or ZnT8). The presence of autoantibodies is known to convey a clearly increased risk of progressing to T1D, particularly when two or more antibody types are present. It remains a point of discussion whether screening efforts are cost-effective. At present, in the absence of interventions capable of delaying the onset of disease, the only benefit of screening is the earlier diagnosis of T1D, thus avoiding life-threatening diabetic ketoacidosis (DKA). Nevertheless, large consortia (e.g., INNODIA and TrialNet) are currently focusing on not only disease biomarkers but also biomarkers of therapeutic effect of interventions. All hope is thus focused on the arrival of intervention strategies that could arrest the ongoing immune destruction of the beta cell and thus delay clinical disease onset. Thus far, attempts have focused on either protecting the beta cell or arresting the immune response, but the future seems to be one of combination therapy. Here, we perform a scoping review on the pathogenesis of T1D, discuss screening strategies, and present promising intervention strategies.

Keywords

Type 1 diabetes / prevention / intervention / cure

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