Thottam Gabrielle E, Krasnokutsky Svetlana, Pillinger Michael H
Department of Medicine, Roger Williams Medical Center, Providence, RI, USA.
Crystal Diseases Study Group, Division of Rheumatology, Department of Medicine, New York University School of Medicine, 301 East 17th Street, Suite 1410, New York, NY, 10003, USA.
Curr Rheumatol Rep. 2017 Aug 26;19(10):60. doi: 10.1007/s11926-017-0688-y.
The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities.
Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.
随着每一项新的研究，痛风的复杂性不断被揭示。痛风处于多个本质上复杂的过程的交叉点，其患病率、对医疗成本的影响以及与重要合并症的关联使其越来越受到关注。痛风与2型糖尿病、高血压、高脂血症、心血管疾病、肾脏疾病和肥胖之间的关联表明，痛风或其必要的前驱高尿酸血症可能在代谢综合征的表现中起重要作用。在本综述中，我们通过回顾痛风与其主要合并症的生理和流行病学关系，分析痛风与代谢综合征之间的复杂相互联系。
越来越多的证据支持痛风与代谢综合征的关联。更具体地说，人体研究和动物模型均表明，高尿酸血症可能在促进炎症、高血压和心血管疾病、脂肪生成和脂质生成、胰岛素和葡萄糖调节异常以及肝脏疾病中发挥作用。果糖摄入与高血压、体重增加、糖耐量受损和血脂异常的发生率增加有关，并且是尿酸生物合成的关键驱动因素。AMP激酶（AMPK）是倾向于减轻代谢综合征的过程的核心调节因子。在肝细胞、白细胞和其他细胞内，果糖/尿酸代谢循环驱动AMPK的关键抑制剂，包括AMP脱氨酶和果糖激酶，这可能使代谢综合征进展的平衡向倾斜。初步证据表明，阻断尿酸细胞内合成的药物可能恢复AMPK活性并有助于维持代谢稳态。痛风既是一种炎症性疾病，也是一种代谢性疾病。随着对尿酸作用的进一步研究，适当管理痛风进而减轻代谢综合征的可能性是一个不断发展且重要的问题。
