In our DIABHONEY study, we examined the impact of partial remission on blood glucose control in 189 children with type 1 diabetes. With this study, we observed positive effects at 6 months for long-lasting remissions, but these effects were no longer present at 1 year: therefore, remission has a positive short-term impact, but likely not a long-term one.

We also conducted a multiparametric analysis of the pancreas in children and adolescents newly diagnosed with type 1 diabetes, which revealed a significant reduction (50%) in pancreatic volume compared to matched controls. This decrease is correlated with a decline in digestive enzyme secretion, suggesting that pancreatic involvement at diagnosis affects the exocrine compartment as well, not just the endocrine function as previously assumed.

As part of the EPHICA 8 study, we introduced the concept of « post-hypoglycemic hyperglycemia » (PHH), a systematic transition from hypoglycemia to hyperglycemia, in children with type 1 diabetes. We also investigated factors that may influence the characteristics of PHH in a cohort of young patients with established type 1 diabetes. This allowed us to demonstrate that PHH is an important component of glycemic imbalance, with different profiles depending on age and body size: younger and leaner children experience more PHH episodes, while adolescents and overweight children experience more prolonged forms. This phenomenon is now being studied in depth within the context of the diabetes remission phase.

Through the Epi-GLUREDIA program, our group has generated one of the most comprehensive assessments of severe hypoglycemia in children with type 1 diabetes. We demonstrated that severe hypoglycemia remains an important clinical burden despite widespread use of diabetes technologies and identified major shortcomings in its prevention and emergency management. Building on these findings, we developed predictive models capable of identifying children at highest risk for severe hypoglycemia and demonstrated the clinical and economic benefits of intranasal glucagon in routine pediatric practice. Together, these studies provide the foundations for individualized prevention strategies and safer diabetes care.

Why this matters

This research is vital because it exposes critical gaps in current pediatric diabetes care, proving that modern technology alone isn’t enough to protect children from severe hypoglycemia. By introducing predictive models and validating the real-world benefits of intranasal glucagon, it shifts the medical approach from reactive emergency response to proactive, personalized prevention—ultimately saving lives and reducing healthcare costs.

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To cure T1D, strategies must be found to restore the ability to secrete insulin spontaneously. Thus, two research areas are possible: finding a way to preserve β-cells after disease onset or successfully regenerating them once they are destroyed.

Current strategies to preserve β-cell mass—including immunotherapy and vaccination—have generally not shown significant effects on disease control in terms of HbA1C levels. Replacing pancreatic β-cells for T1D appears feasible. Islet transplantation works but depends on the limited availability of organ donors.

Our group has discovered a new pancreatic cell progenitor capable of producing new β-cells in vitro and reducing glucose levels in diabetic animals after transplantation. We previously demonstrated the ability to derive cells from purified human pancreatic ducts that can produce large quantities of reprogrammable cells. Recent developments in our research have shown the possibility of inducing these human duct-derived cells to functional insulin secretion after treatment with the transcription factor MAFA. Our modified RNA transfection protocol for MAFA achieved 37% of HDDCs expressing β-cell characteristics, including functional insulin secretion and the ability to reduce hyperglycemia after transplantation in diabetic mice.

Our study represents one of the pioneering works demonstrating the possibility of transdifferentiating human somatic cells into functional cells with curative potential, using a non-integrative, reliable, cost-effective, and specific system based on smRNA. smRNAs also have the advantage of being deliverable in situ.

Why this matters

This study is important because it demonstrates a safe, non-viral method to reprogram human adult cells into functional, insulin-secreting beta cells. This offers a promising new strategy for cell-replacement therapy in type 1 diabetes without the ethical and safety issues associated with stem cells. This technology could also potentially lead to reversal of T1D.

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It is understood that β-cell destruction occurs through cytokine secretion and the activation of specific receptors and lymphocytes. A current objective of our research is to evaluate whether knockdown strategies targeting key protein components of islet inflammation could be combined with pharmacological reduction of glucotoxicity in an effort to protect β-cell mass from destruction during the early events leading to β-cell loss in T1D.

In a subsidiary study of this research project, we evaluated whether glucotoxicity could contribute to the destruction of β-cell mass by participating in inflammation of the islets of Langerhans. We assessed the potential of empagliflozin and GABA to protect β-cell mass against glucotoxicity and to increase β-cell mass after T1D diagnosis. In a streptozotocin-treated mouse model of T1D, we observed that empagliflozin and/or GABA had the potential to improve glucose homeostasis and pancreatic insulin content in treated animals compared to diabetic controls. We noted that the effects of empagliflozin were associated with a reduction in islet ER stress and inflammation, while in mice treated with both empagliflozin and GABA, β-cell mass increased following an initial surge in α-cell compartment proliferation. Our next goal is to evaluate whether these effects of empagliflozin and GABA can be translated into longer-term protocols in the Non-Obese Diabetic (NOD) mouse model.

Why this matters

This study is important because it demonstrates a dual-action therapeutic strategy that shifts the paradigm from merely managing symptoms to actively halting pancreatic destruction and reversing the progression of T1D. Furthermore, by successfully triggering the body’s own cells to multiply and restore insulin-producing capacity, it provides a viable, non-invasive blueprint for regenerating functional pancreatic tissue and permanently recovering glucose control from within.

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During physical activity, patients with T1D face various challenges in maintaining normal blood glucose levels. As part of the TREAD-DIAB 16 study, we evaluated the needs of children and adolescents regarding insulin and carbohydrate adjustments during exercise. We developed an algorithm that helps us precisely tailor insulin and carbohydrate intake during exercise sessions, specifically for each patient. Our results showed that it was possible to normalize blood glucose levels in patients using insulin pumps. Since this proved more difficult in young patients on insulin injections, we conducted a new study (CAR2DIAB) to assess whether we could provide fine-tuned adjustments of insulin injections and carbohydrate intake for all diabetic patients. In this pediatric study, applying algorithmic and individualized treatment adjustments overall improved glycemic control for up to 15 hours following real-life exercise sessions performed by children and adolescents (n=12) with T1D 17. We are currently expanding this study to a larger group of patients (CAR2DIAB-2 study).

Why this matters

Physical activity is essential for adolescents with T1D, but exercise could make it difficult to predict and manage blood glucose levels. 

These findings brings us closer to more precise and practical diabetes management during sports and physical activity, ensuring potential safety and support in healthier and more active lifestyle for people living with T1D. 

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Diabetes refers to a heterogeneous group of diseases with diverse origins and distinct therapeutic options. Beyond the two main forms of diabetes (T1D and T2D), there are rare subtypes called monogenic diabetes (or MODY), which are difficult to diagnose due to their resemblance to T1D or T2D. Since these monogenic diabetes forms can appear early in life, a consortium of expert pediatric clinical centers was established as part of a clinical research initiative to develop tools for accurate diagnosis of rare diabetes types and to provide appropriate care for children and adolescents who are often misdiagnosed with T1D or T2D (GENEPEDIAB study).

Our pediatric initiative, called the GENEPEDIAB study, brought together six diabetes reference centers in the French-speaking part of Belgium. We created a new score (DIAMODIA), based on typical clinical features, to identify patients with atypical diabetes. To date, among 1,550 patients diagnosed with « type 1 or type 2 diabetes, » we isolated a subgroup of 149 patients presenting atypical forms of diabetes (called the « ADia cohort »). This ADia cohort underwent stepwise genetic screening to search for a potential molecular diagnosis. Routine analysis of the MODY gene panel identified 34 patients with a class V variant (the « MODY cohort »). In-depth whole exome sequencing (WES) analysis identified 37 ADia patients with a class III variant, resulting in a DIAMODIA score yield of 31% for class V variant positivity and 34% for class III variant positivity. Our DIAMODIA score was validated on a MODY cohort (compared to a typical T1D cohort) to ensure the external validity and predictive value of this new tool for diagnosing patients carrying a potential genetic variant.

Why this matters

Our research has shown that childhood diabetes extends beyond the classical distinction between autoimmune type 1 diabetes and monogenic diabetes. Through the GENEPEDIAB study, we characterized the clinical spectrum of atypical diabetes and demonstrated that many children occupy an intermediate phenotype requiring a more individualized diagnostic approach.

Based on these observations, we developed clinical tools that improve the identification of patients likely to harbor pathogenic genetic variants, thereby facilitating precision diagnosis and personalized treatment.

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Our discoveries extend beyond type 1 diabetes. We identified risk factors for dysglycemia after pediatric liver and kidney transplantation, characterized treatment-induced hyperglycemia in childhood cancers, and improved the understanding of thyroid dysfunction associated with amiodarone therapy.

In rare endocrine diseases, our work has contributed to elucidating the clinical and genetic basis of adrenal disorders, Cushing syndrome, growth disorders, and inherited endocrine syndromes, helping to refine diagnosis and optimize patient management.

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