Hyperuricemia and cardiometabolic disease: current evidence linking uric acid to obesity, insulin resistance and type 2 diabetes mellitus

Abstract

Hyperuricemia has long been regarded as the biochemical hallmark of gout; however, accumulating evidence indicates that its clinical relevance extends considerably beyond crystal-induced arthropathy. Elevated serum uric acid levels are increasingly encountered in individuals with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease, positioning hyperuricemia as a potentially integral component of the cardiometabolic continuum. This narrative review synthesizes current evidence linking serum uric acid to obesity, insulin resistance, T2DM, and cardiovascular risk. Epidemiological data consistently demonstrate robust associations between uric acid levels and adverse cardiometabolic profiles. Complementary experimental findings support plausible pathogenic mechanisms, including oxidative stress, mitochondrial dysfunction, endothelial injury, chronic low-grade inflammation, and activation of the renin-angiotensin-aldosterone system. Special emphasis is placed on the bidirectional relationship between obesity and hyperuricemia, the metabolic consequences of fructose overconsumption, and the emerging utility of uric acid as a predictor of incident metabolic disease. The question of whether hyperuricemia acts primarily as a marker or an active mediator of cardiometabolic dysfunction remains unresolved; current evidence, however, supports a contributory pathophysiological role. A deeper understanding of uric acid metabolism may enhance cardiometabolic risk stratification and inform the development of targeted preventive and therapeutic strategies.