Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity

Marc Donath, MD
Professor & Endocrinologist
Université de Montréal
Université de Montréal Hospital Research Centre (CRCHUM)
Medical Director 
Integrated Centre of Excellence in Metabolic Health (CEISM)
McGill University Health Centre (MUHC)

This conference is hosted by Rémi Rabasa-Lhoret, MD, PhD, Director, Metabolic Diseases Research Unit | Director of the Diabetes Clinic. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
Increased activity of the NLRP3 inflammasome–IL-1β pathway is observed in obesity and contributes to the development of type 2 diabetes and its complications. In my presentation, I will discuss the pathological activation of IL-1β by metabolic stress, ageing and the microbiome and present data on the role of IL-1β in metabolism. I will explore the physiological role of the IL-1β pathway in insulin secretion and the relationship between circulating levels of IL-1β and the development of diabetes and associated diseases. I will highlight the paradoxical nature of IL-1β as both a friend and a foe in glucose regulation and provide details on clinical translation, including the glucose-lowering effects of IL-1 antagonism and its impact on disease modification. I will also discuss the potential role of IL-1β in obesity, Alzheimer's disease, fatigue, gonadal dysfunction and related disorders such as rheumatoid arthritis and gout. Finally, I will address the safety of NLRP3 inhibition and IL-1 antagonists and the prospect of using this therapeutic approach for the treatment of type 2 diabetes and its comorbidities.

About Marc Donath
Dr. Marc Donath is Medical Director of the Integrated Centre of Excellence in Metabolic Health at the Université de Montréal Hospital. He has made numerous contributions to our understanding of the pathogenesis of type 2 diabetes, his most important being the identification of an inflammatory process underlying failure of insulin production in this disease. Thereby he showed that metabolic stress induces an IL-1β mediated immune response. He confirmed this hypothesis in the first clinical study showing that modulation of the immune system may improve metabolism and cardiovascular diseases in patients with type 2 diabetes. His work has contributed to the concept that the innate immune system is an integral component in the regulation of metabolism, i.e. immunometabolism.

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