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Figure 1. Pathogenesis of type 1 diabetes. In a genetically predisposed individual, a sudden trigger results in beta cell dysfunction or
aberrant activation of the immune system, as depicted by the upper blue arrows. This eventually results in the destruction of the beta
cells. Beta cell dysfunction can also trigger a (healthy) immune response to clear the dysfunctional beta cells (depicted by double-
headed arrows). In a similar way, beta cell destruction by the immune system will cause stress on the remaining beta cells, resulting in
further beta cell apoptosis. APC: Antigen-presenting cell; ER: endoplasmic reticulum; GAD: glutamic acid decarboxylase; IA2: islet-
antigen 2; Treg: regulatory T cell; ZnT8: zinc-transporter 8.

collection of samples, followed by highly standardized and quality-controlled analyses in accredited
laboratories, should allow robust conclusions when performing an integrated multi-omics natural history
study on samples of new-onset T1D individuals or antibody-positive first-degree relatives of people with
T1D. Of importance, these biomarker analyses are also included in the clinical trials running in the
INNODIA network, thus not only opening the path to biomarkers of disease but also raising hope for the
discovery of biomarkers of therapeutic effect and success of interventions.

PREVENTION OR ARREST OF TYPE 1 DIABETES: ARE WE THERE YET?
Why have we not cured T1D yet? It is not because of a lack of trying. The list of studies already performed
in people with new-onset T1D or unaffected high-risk family members is already very long. In an attempt to
exploit resources and efforts, the scientific community, together with pharmaceutical companies and patient
advisors, have joined globally into large consortia. Examples include the Type 1 Diabetes TrialNet
[established in 2001 as a National Institutes of Health (NIH)-funded and Juvenile Diabetes Research
Foundation (JDRF)-supported international clinical trial network that emerged from the Diabetes
Prevention Trial Type 1 (DPT-1)] and the more recent INNODIA consortium (a European partnership
among academic institutions, industrial partners, and patient organizations) . These consortia have the
[32]
advantage of being multi-centered and often have a master protocol, allowing comparison between different
studies.

To date, interventions mainly focused on either targeting an ongoing immune response by general or
specific immune suppression or modulation [Table 1] or the induction of tolerance to beta cell-related