Yang Tianshu, Luo Lingyun, Luo Xuelian, Liu Xiaolei
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 Hubei, China.
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 Hubei, China; Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030 Hubei, China.
Diabetes Res Clin Pract. 2025 Jun;224:112204. doi: 10.1016/j.diabres.2025.112204. Epub 2025 Apr 26.
Hyperuricemia and diabetes mellitus (DM) are prevalent metabolic disorders with high comorbidity, imposing a substantial global public health burden. Their coexistence is not merely additive but synergistic, exacerbating metabolic dysregulation through mechanisms such as insulin resistance and β-cell apoptosis, ultimately establishing a vicious cycle. Both disorders induce acute and chronic damage to vital organs, particularly the cardiovascular, renal systems. Hyperuricemia aggravates diabetic complications, notably diabetic cardiomyopathy, nephropathy and retinopathy via oxidative stress, inflammation, and metabolic dysregulation.Current urate-lowering therapies (ULTs), such as xanthine oxidase inhibitors and urate transporter 1 (URAT1, also known as SLC22A12) antagonists, demonstrate potential benefits in ameliorating diabetic complications but face challenges including safety concerns and dose adjustments. Similarly, several glucose-lowering drugs also exhibit the benefits of improving hyperuricemia. This review summarizes the metabolic crosstalk and therapeutic interplay between hyperuricemia and DM, examines the pathogenic role of uric acid in diabetic complications, and discusses the benefits and challenges of existing ULTs and glucose-lowering drugs in disrupting this cycle of metabolic dysregulation and concurrent organ damage. We hope our findings deepen the comprehension of the intricate metabolic crosstalk between glucose and urate homeostasis, providing novel therapeutic insights for patients with comorbid DM and hyperuricemia.
高尿酸血症和糖尿病（DM）是常见的代谢紊乱疾病，合并症发生率高，给全球公共卫生带来了沉重负担。它们的共存不仅是相加的，而且是协同的，通过胰岛素抵抗和β细胞凋亡等机制加剧代谢失调，最终形成恶性循环。这两种疾病都会对重要器官，尤其是心血管和肾脏系统造成急性和慢性损害。高尿酸血症通过氧化应激、炎症和代谢失调加重糖尿病并发症，特别是糖尿病性心肌病、肾病和视网膜病变。目前的降尿酸治疗（ULTs），如黄嘌呤氧化酶抑制剂和尿酸转运蛋白1（URAT1，也称为SLC22A12）拮抗剂，在改善糖尿病并发症方面显示出潜在益处，但面临包括安全性问题和剂量调整在内的挑战。同样，几种降糖药物也表现出改善高尿酸血症的益处。本综述总结了高尿酸血症和糖尿病之间的代谢相互作用和治疗相互影响，探讨了尿酸在糖尿病并发症中的致病作用，并讨论了现有ULTs和降糖药物在打破这种代谢失调和并发器官损害循环方面的益处和挑战。我们希望我们的发现能加深对葡萄糖和尿酸稳态之间复杂代谢相互作用的理解，为糖尿病和高尿酸血症合并症患者提供新的治疗思路。
