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challenging due to the large cohorts and long follow-up needed. In the future, the combined use of immune
interventions together with beta cell augmenting and/or replacement therapy, such as stem cell-based
therapy, might offer a solution to compensate for the lost beta cell function at the time of clinical diagnosis.

CONCLUSIONS
Type 1 diabetes remains one of the most common and severe chronic diseases in children, adolescents, and
young adults. However, despite its high prevalence, we keep on using a standard therapy that is already
more than a century old. Technological advances have helped make giant strides in regulating optimal
glucose homeostasis, but the chronic burden of long-term hyperglycemia-related complications remains
troublesome. Despite all efforts, the road to a cure for T1D remains long and full of obstacles. The first is the
need for biomarkers allowing early screening. The second is the need for superior treatment options, as this
pursuit for early biomarkers should not turn into a Sword of Damocles. Whereas interventions thus far have
mainly focused on either targeting the ongoing immune response or the induction of tolerance to the beta
cell, we believe future research should focus on targeting both. A limitation to this review is that the field of
T1D research is extensive and ever ongoing (as the long list of currently ongoing trials shows). Nevertheless,
we hope this review shows that the pursuit of early biomarkers can go hand in hand with superior treatment
options, as early screening can result in an earlier treatment initiation at a time of a higher residual
functional beta cell mass. Thus, when asking the question, “Are we there yet?”, we have to say, “Not yet”.
However, the future does look bright as we have high hopes for the trend towards global consortia as joined
effort and pooled resources hopefully have a synergistic effect.

DECLARATIONS
Authors’ contributions
Conceptualized the review goals and wrote the manuscript: Mathieu C, Martens PJ
All authors contributed to the article, consent to participate and approved the submitted version.

Availability of data and materials
The data that support the findings of this study are openly available in PubMed at
https://pubmed.ncbi.nlm.nih.gov/.

Financial support and sponsorship
This work was supported by IMI2-JU under grant agreements 115797 (INNODIA) and 945268 (INNODIA
HARVEST). This joint undertaking receives support from the European Union’s Horizon 2020 research
and innovation program and European Federation of Pharmaceutical Industries and Associations, JDRF,
and The Leona M. and Harry B. Helmsley Charitable Trust and KU Leuven (C16/18/006). This publication
was supported by the Open Access Publication Fund of the KU Leuven.

Conflicts of interest
The authors declared that the research was conducted in the absence of any commercial or financial
relationships that could be construed as a potential conflict of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.