Review
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World J Diabetes. Dec 15, 2014; 5(6): 787-795
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.787
Linking uric acid metabolism to diabetic complications
Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu
Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Tokyo 103-0002, Japan
Author contributions: All authors contributed to this work.
Correspondence to: Akifumi Kushiyama, MD, PhD, Assistant Division Chief, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Nihonbashi Bakurocho, Chuo-ku, Tokyo 103-0002, Japan. kusiyaa-tky@umin.ac.jp
Telephone: +81-3-36395501 Fax: +81-3-36395520
Received: August 31, 2014
Revised: October 22, 2014
Accepted: November 7, 2014
Published online: December 15, 2014
Processing time: 103 Days and 23.3 Hours
Abstract

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

Keywords: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism

Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.