Background: Uric acid is the end product of purine metabolism and serves as a major antioxidant in human plasma. While physiological concentrations may be protective, elevated serum uric acid has been increasingly associated with insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. The role of uric acid as a causal factor in cardiometabolic syndrome remains controversial. Methods: This narrative review examined evidence from epidemiological studies, experimental animal models, genetic analyses, and clinical trials that investigated the relationship between serum uric acid and cardiometabolic syndrome and its components. Emphasis was placed on mechanistic pathways and clinical implications of hyperuricemia. Results: Most prospective and experimental studies indicate that elevated serum uric acid frequently precedes the development of insulin resistance and type 2 diabetes mellitus and is independently associated with cardiometabolic syndrome. Mechanistic evidence suggests that uric acid contributes to endothelial dysfunction through reduced nitric oxide bioavailability, increased oxidative stress, inflammation, and impaired insulin signaling. Hyperuricemia has also been linked to hypertension, renal dysfunction, and hepatic triglyceride accumulation via pathways involving mitochondrial dysfunction and inhibition of AMP-activated protein kinase. Pharmacological reduction of uric acid has been associated with improvement in cardiometabolic parameters in experimental models and selected clinical studies. Conclusion: Current evidence supports a contributory role of elevated uric acid in the development of cardiometabolic syndrome. Uric acid may represent a modifiable risk factor and a potential therapeutic target in cardiometabolic disorders.
Dangana et al. (Mon,) studied this question.