Searching for the cause of type 2 diabetes has been a prime area of research since Etienne Lancereaux described fat diabetes (diabetes gras) in 1880. Though more studies are needed, the evidence that fructose-induced hyperuricemia may have a contributory role is gaining ground. While it still remains a hypothesis, increasing evidence suggests uric acid may have a fundamental role in the manifestations of metabolic syndrome (Fig. 3). Given that hyperuricemia is a remediable risk factor, we recommend both basic and clinical studies to address this important possibility.
Uric acid: potential mechanisms for insulin resistance and diabetes. Uric acid may contribute to insulin resistance in the liver by inducing mitochondrial oxidative stress and steatosis. Uric acid also blocks the ability of insulin to stimulate vasodilation of blood vessels, which is important for the delivery of glucose to the skeletal muscle.[4,32] Uric acid also induces local inflammation in the adipose tissue with a reduction in the production of adiponectin. Finally, uric acid may also have direct effects on the islet cells leading to local oxidative stress and islet dysfunction. Mt, mitochondria; PO4, phosphate.
Support for this study was provided by ADA Basic Science Award 7-12-BS-16 to Y.Y.S.
R.J.J. has patent applications related to lowering uric acid as a means to prevent or treat insulin resistance and features of metabolic syndrome; holds stock in XORT Pharma Corp.; and is on the Scientific Board of Amway. T.N. has patent applications related to lowering uric acid as a means to prevent or treat insulin resistance and features of metabolic syndrome and holds stock in XORT Pharma Corp. No other potential conflicts of interest relevant to this article were reported.
R.J.J. wrote the first draft of the manuscript. T.N., L.G.S.-L., M.S., S.S., M.L., T.I., Y.Y.S., and M.A.L. improved the manuscript with their comments and suggestions. In addition, all of the authors have made scientific contributions that provided the groundwork for this Perspective.
Diabetes. 2013;62(10):3307-3315. © 2013 American Diabetes Association, Inc.