Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Teijin Pharma Limited, Tokyo, Japan.
J Diabetes Investig. 2019 Jan;10(1):94-103. doi: 10.1111/jdi.12870. Epub 2018 Jul 7.
AIMS/INTRODUCTION: There is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally- and systemically-activated xanthine oxidase (XO), a rate-limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus and metabolic syndrome (MetS).
We enrolled 60 patients with type 2 diabetes mellitus and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly-sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters.
The value of plasma XO activity was correlated with indices of insulin resistance and the level of circulating liver transaminases. In contrast, the level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with the serum uric acid level.
Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and MetS. Through assessing the plasma XO activity, patients showing normal levels of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncovering metabolic risks in type 2 diabetes mellitus and MetS patients.
目的/引言:高尿酸血症是否是心血管代谢疾病的独立危险因素存在争议。尿酸的血清水平受多种参与其生成和排泄的因素影响。相比之下,有证据表明,局部和全身激活的黄嘌呤氧化酶(XO),即尿酸生成的限速酶,与人类和啮齿动物的代谢紊乱有关。因此,我们探讨了 2 型糖尿病和代谢综合征(MetS)患者血浆 XO 活性的临床意义。
我们招募了 60 名 2 型糖尿病和 MetS 患者。MetS 根据 2005 年国际糖尿病联合会指南定义。通过高度敏感的荧光法测量黄嘌呤氧化酶的转化来测量血浆 XO 活性,并探讨了血浆 XO 活性值与代谢参数之间的关系。
血浆 XO 活性值与胰岛素抵抗指数和循环肝转氨酶水平相关。相比之下,血清尿酸水平与胰岛素抵抗指数不相关。血浆 XO 活性值与血清尿酸水平不相关。
在日本 2 型糖尿病和 MetS 患者中,血浆 XO 活性与胰岛素抵抗和肝功能障碍指数相关。通过评估血浆 XO 活性,可以筛选出血清尿酸水平正常但 XO 活性较高的患者,从而为发现 2 型糖尿病和 MetS 患者的代谢风险提供线索。