Yan Wei, Wen Song, Zhou Ligang
Department of Endocrinology, Shanghai Pudong Hospital, n University, Shanghai, 201399, People's Republic of China.
Department of General Practice, Jinshan Hospital, Fudan University, Shanghai, 201508, People's Republic of China.
Diabetes Metab Syndr Obes. 2023 Sep 29;16:3029-3044. doi: 10.2147/DMSO.S429068. eCollection 2023.
This article examined the current research on hyperuricemia (HUA) exacerbating diabetic kidney damage and novel anti-diabetic medications for treating these people. Hyperuricemia and type 2 diabetes (T2D), both of which are frequent metabolic disorders, are closely connected. Recent studies have shown that hyperuricemia can increase kidney injury in T2D patients by aggravating insulin resistance, by activating the renin-angiotensin-aldosterone system (RAAS), and by stimulating inflammatory factors, and the diversity, distribution, and metabolites of intestinal flora. Considering this, there are just a few of the research examining the effect of hyperuricemia on diabetic kidney injury via intestinal flora. Through the gut-kidney axis, intestinal flora primarily influences renal function. The primary mechanism is that variations in diversity, distribution, and metabolites of intestinal flora led to alterations in metabolites (such as short-chain fatty acids, Indoxyl sulfate and p-cresol sulfate, Trimethylamine N-oxide TMAO). This article reviewed the research and investigates the association between hyperuricemia and T2D, as well as the influence of hyperuricemia on diabetic kidney injury via intestinal flora. In addition, the current novel antidiabetic drugs are discussed, and their characteristics and mechanisms of action are reviewed. These novel antidiabetic drugs include SGLT2 inhibitors, GLP-1 receptor agonists, DDP-4 inhibitors, glucokinase (GK) enzyme activators (GK agonists), and mineralocorticoid receptor antagonists (MRA). Recent studies suggest that these new anti-diabetic medications may have a therapeutic effect on hyperuricemia-induced kidney impairment in diabetes patients via various mechanisms. Some of these medications may reduce blood uric acid levels, while others may improve kidney function by attenuating the overstimulation of RAAS or by decreasing insulin resistance and inflammation in the kidneys. These novel antidiabetic medicines may have a multifaceted approach to treating hyperuricemia-induced kidney impairment in diabetic patients; nevertheless, additional study is required to establish their efficacy and comprehend their specific mechanisms.
本文探讨了高尿酸血症（HUA）加重糖尿病肾损伤的当前研究以及用于治疗此类患者的新型抗糖尿病药物。高尿酸血症和2型糖尿病（T2D）均为常见的代谢紊乱疾病，二者联系紧密。近期研究表明，高尿酸血症可通过加重胰岛素抵抗、激活肾素 - 血管紧张素 - 醛固酮系统（RAAS）、刺激炎症因子以及影响肠道菌群的多样性、分布和代谢产物，增加T2D患者的肾损伤。鉴于此，仅有少数研究探讨高尿酸血症通过肠道菌群对糖尿病肾损伤的影响。肠道菌群主要通过肠 - 肾轴影响肾功能。其主要机制是肠道菌群多样性、分布和代谢产物的变化导致代谢产物（如短链脂肪酸、硫酸吲哚酚和对甲酚硫酸盐、氧化三甲胺TMAO）发生改变。本文回顾了相关研究，探讨了高尿酸血症与T2D之间的关联，以及高尿酸血症通过肠道菌群对糖尿病肾损伤的影响。此外，还讨论了当前的新型抗糖尿病药物，并综述了其特点和作用机制。这些新型抗糖尿病药物包括钠 - 葡萄糖协同转运蛋白2（SGLT2）抑制剂、胰高血糖素样肽 - 1（GLP - 1）受体激动剂、二肽基肽酶 - 4（DDP - 4）抑制剂、葡萄糖激酶（GK）激活剂（GK激动剂）和盐皮质激素受体拮抗剂（MRA）。近期研究表明，这些新型抗糖尿病药物可能通过多种机制对糖尿病患者高尿酸血症所致的肾损害具有治疗作用。其中一些药物可能降低血尿酸水平，而另一些药物可能通过减弱RAAS的过度刺激或降低肾脏中的胰岛素抵抗和炎症来改善肾功能。这些新型抗糖尿病药物可能对糖尿病患者高尿酸血症所致的肾损害具有多方面的治疗作用；然而，需要进一步研究以确定其疗效并了解其具体机制。
