The Role of NLRP3 Inflammasome in Type 2 Diabetes Mellitus and Its Macrovascular Complications

Abstract

Diabetes Mellitus (DM) is among the most common non-infectious causes of death globally, with Type 2 DM (T2DM) representing the majority of cases. T2DM is primarily characterized by insulin resistance, leading to hyperglycemia and compensatory hyperinsulinemia. Rapid changes in lifestyle, technological advancement, and societal evolution have fueled a global rise in T2DM, making it a major public health concern. The condition is associated with numerous complications-both macrovascular and microvascular-including coronary artery disease, heart failure, chronic kidney disease, and diabetic retinopathy, all of which contribute to increased morbidity and early mortality. Chronic tissue inflammation is now recognized as a key factor in the development of T2DM, with elevated inflammatory markers serving as predictors of the disease. In particular, the NLRP3 inflammasome complex has emerged as a central player in this inflammatory process. NLRP3 acts as an intracellular sensor for danger signals and tissue injury, triggering inflammatory responses and contributing to endothelial dysfunction and T2DM pathogenesis. Its role in linking metabolic stress to inflammation has positioned it as a promising therapeutic target. This review focuses on the mechanisms underlying NLRP3 inflammasome activation and its role in T2DM and related vascular complications. Additionally, it highlights emerging therapies that target NLRP3, offering new potential strategies for the prevention and treatment of T2DM.

Keywords: NLRP3 inflammasome; diabetes mellitus; inflammation.

Figure 1

NLRP3 inflammasome inhibitors tested in the cardiovascular system and their site of action.