Urinary albumin-to-creatinine ratio (ACR) is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR, but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR. The association between ACR and microvascular function (responses to acetylcholine [ACH] and sodium nitroprusside) was tested in the SUMMIT study. Two-sample Mendelian randomization (MR) was used to infer the causal effects of 11 metabolic risk factors, including glycemic, lipid, and adiposity traits, on ACR. MR was performed in up to 440,000 UK Biobank and 54,451 CKDGen participants. ACR was robustly associated with microvascular function measures in SUMMIT. Using MR, we inferred that higher triglyceride (TG) and LDL cholesterol (LDL-C) levels caused elevated ACR. A 1 SD higher TG and LDL-C level caused a 0.062 (95% CI 0.040, 0.083) and a 0.026 (95% CI 0.008, 0.044) SD higher ACR, respectively. There was evidence that higher body fat and visceral body fat distribution caused elevated ACR, while a metabolically “favorable adiposity” phenotype lowered ACR. ACR is a valid marker for microvascular function. MR suggested that seven traits have causal effects on ACR, highlighting the role of adiposity-related traits in causing lower microvascular function.

中文翻译：

---

孟德尔随机研究提供证据表明肥胖和血脂异常导致尿白蛋白肌酐比降低，这是微血管功能的标志

尿白蛋白与肌酐比值 (ACR) 是糖尿病肾病和微血管损伤的标志物。代谢相关性状在观察上与 ACR 相关，但其因果作用尚不确定。在这里，我们确认 ACR 是微血管损伤的标志物，并测试了代谢相关性状是否与 ACR 有因果关系。在 SUMMIT 研究中测试了 ACR 与微血管功能（对乙酰胆碱 [ACH] 和硝普钠的反应）之间的关联。两样本孟德尔随机化 (MR) 用于推断 11 种代谢风险因素对 ACR 的因果影响，包括血糖、脂质和肥胖特征。MR 在多达 440,000 名英国生物银行和 54,451 名 CKDGen 参与者中进行。ACR 与 SUMMIT 中的微血管功能测量密切相关。使用 MR，我们推断较高的甘油三酯 (TG) 和低密度脂蛋白胆固醇 (LDL-C) 水平会导致 ACR 升高。TG 和 LDL-C 水平升高 1 SD 分别导致 ACR 升高 0.062 (95% CI 0.040, 0.083) 和 0.026 (95% CI 0.008, 0.044) SD。有证据表明，较高的体脂和内脏体脂肪分布导致 ACR 升高，而代谢“有利肥胖”表型降低了 ACR。ACR 是微血管功能的有效标志物。MR 提出七种性状对 ACR 有因果影响，突出了肥胖相关性状在导致微血管功能降低中的作用。有证据表明，较高的体脂和内脏体脂肪分布导致 ACR 升高，而代谢“有利肥胖”表型降低了 ACR。ACR 是微血管功能的有效标志物。MR 提出七种性状对 ACR 有因果影响，突出了肥胖相关性状在导致微血管功能降低中的作用。有证据表明，较高的体脂和内脏体脂肪分布导致 ACR 升高，而代谢“有利肥胖”表型降低了 ACR。ACR 是微血管功能的有效标志物。MR 提出七种性状对 ACR 有因果影响，突出了肥胖相关性状在导致微血管功能降低中的作用。