Uric Acid as a Cause of the Metabolic Syndrome

Abstract

Hyperuricemia is common in subjects with obesity, metabolic syndrome, and type 2 diabetes. For many years, hyperuricemia was attributed to the effects of insulin resistance to reduce urinary excretion of uric acid, and it was believed that uric acid may not have any causal role in the metabolic syndrome. However, in recent years, hyperuricemia has been found to independently predict the development of diabetes. Experimental studies have also shown that hyperuricemia may mediate insulin resistance, fatty liver, and dyslipidemia in both fructose-dependent and fructose-independent models of metabolic syndrome. The mechanism for uric acid-induced insulin resistance appears to be mediated by the development of mitochondrial oxidative stress and impairment of insulin-dependent stimulation of nitric oxide in endothelial cells. Pilot studies in humans have reported a potential benefit of lowering serum uric acid on insulin resistance. Large clinical trials are recommended. If uric acid is shown to be a mediator of incident type 2 diabetes in humans, then lowering serum uric acid would represent a simple and inexpensive way to help prevent the development of diabetes and to slow the epidemic.