Our discoveries

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.

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.

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.

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).

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.