Interrelationship of Uric Acid, Gout, and Metabolic Syndrome: Focus on Hypertension, Cardiovascular Disease, and Insulin Resistance

Seong-Kyu Kim

doi:10.4078/jrd.2018.25.1.19

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Kim: Interrelationship of Uric Acid, Gout, and Metabolic Syndrome: Focus on Hypertension, Cardiovascular Disease, and Insulin Resistance

Review Article

J Rheum Dis 2018;25(1):19-27.

Published online: 31 October 2018

DOI: https://doi.org/10.4078/jrd.2018.25.1.19

Interrelationship of Uric Acid, Gout, and Metabolic Syndrome: Focus on Hypertension, Cardiovascular Disease, and Insulin Resistance

Seong-Kyu Kim

Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea

Corresponding to: Seong-Kyu Kim, Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. E-mail: kimsk714@cu.ac.kr

Received 28 November 2017 Accepted 29 November 2017

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The mean serum uric acid level and the prevalence of hyperuricemia have increased over the past few decades. Hyperuricemia is considered to be responsible for the increased risk of hypertension, insulin resistance, and cardiovascular disease. Metabolic syndrome also contributes to the development of type II diabetes mellitus and cardiovascular disease. Despite the close relationships between uric acid and the components of metabolic syndrome, the causal effect of uric acid on these clinical issues is unclear. Recent studies have revealed the possible development of metabolic syndrome mediated by fructose-induced hyperuricemia. This review summarizes the available clinical and experimental data supporting the causal effect of uric acid on the components of metabolic syndrome, including hypertension, cardiovascular disease, and insulin resistance.

Keywords: Uric acid, Hyperuricemia, Gout, Metabolic syndrome

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Figure 1.

Uric acid contributes to different component features of metabolic syndrome. RAS: renin-angiotensin system, NO: nitric oxide, GLUT9: glucose transporter 9, MCP-1: monocyte chemoattractant protein-1, PDGFRβ: platelet-derived growth factor receptor beta, AMPK: adenosine monophosphate kinase.

Figure 2.

Mechanisms of insulin resistance by fructose and uric acid. HFCS: high-fructose corn syrup, GLUT5: glucose transporter 5, ATP: adenosine triphosphate, NO: nitric oxide.

Table 1.

Definitions of the metabolic syndrome: comparison of WHO, NCEP ATP III, and IDF classification criteria

Risk factors	WHO [14]	NCEP ATP III [15]	IDF [16]
Criteria	DM/IFG or IGT or IR plus at least two of the following	Any ≥3 of the following 5 criteria	Increased WC (ethnicity specific) plus at least two of the following
Obesity	Waist-to-hip ratio ＞0.90 in men and ＞0.85 in women and/or BMI ＞30 kg/m²	WC ≥102 cm in men or ≥88 cm in women	WC criteria dependent on ethnicity
Triglycerides	≥150 mg/dL	≥150 mg/dL	≥150 mg/dL
HDL cholesterol	＜35 mg/dL in men and ＜39 mg/dL in women	＜40 mg/dL in men and ＜50 mg/dL in women	＜40 mg/dL in men and ＜50 mg/dL in women
Hypertension	≥140/90 mmHg	≥130 mmHg systolic or ≥85 mmHg diastolic	≥130 mmHg systolic or ≥85 mmHg diastolic
Hyperglycemia	IGT, IFG, or type 2 DM	≥100 mg/dL	≥100 mg/dL
Microalbuminuria	＞30 mg albumin/g creatinine

WHO: World Health Organization, NCEP ATP III: National Cholesterol Education Program Adult Treatment Panel III, IDF: International Diabetes Federation, HDL: highdensity lipoprotein, DM: diabetes mellitus, IFG: impaired fasting glucose (fasting plasma glucose level, 100∼125 mg/dL), IGT: impaired glucose tolerance (2 h plasma glucose level after 75 g glucose load, 140∼199 mg/dL), IR: insulin resistance, WC: waist circumference, BMI: body mass index.

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