血清Klotho水平与糖尿病肾病之间的关联：2007 - 2016年美国国家健康与营养检查调查（NHANES）及孟德尔随机化研究结果
Association between the serum Klotho levels and diabetic kidney disease: results from the NHANES 2007-2016 and Mendelian randomization study.
作者信息
Peng Xuankun, Li Shengyuan, Song Yuqian, Luo Yuanyuan, Liu Shuai, Zhao Tongfeng
机构信息
Department of Endocrinology, Guangdong Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510080 PR China.
Department of Endocrinology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000 China.
出版信息
J Diabetes Metab Disord. 2025 Jun 25;24(2):156. doi: 10.1007/s40200-025-01623-7. eCollection 2025 Dec.
OBJECTIVES
The purpose of this research is to clarify the connection between the serum Klotho levels and diabetic kidney disease (DKD) in American adults with diabetes.
METHODS
Statistic from the 2007-2016 National Health and Nutrition Examination Survey was used to explore correlation between Klotho levels and the risk of diabetic kidney disease (DKD) with multivariate linear regression models. Smoothed curve fitting was conducted to find potential non-linear relationships. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing summary statistics from genome-wide association studies (GWAS). The primary method employed was inverse variance weighting (IVW), complemented by additional MR techniques to investigate the causal link between Klotho levels and diabetic kidney disease (DKD). Furthermore, sensitivity analyses were conducted to evaluate the robustness of the findings.
RESULTS
The cross-sectional study included a total of 3,214 individuals with diabetes mellitus from NHANES, with 1,967 of these participants being diagnosed as diabetic kidney disease (DKD).The multivariate logistic regression model showed that the higher the Klotho levels were, the lower incidence of DKD was. The MR results suggested the serum Klotho concentration to be a direct protective factor of diabetic nephropathy (IVW odds ratio (OR): 0.859 (95% confidence interval 0740-0.998), <0.05), which was consistent with conclusion from observational study from NHANES.
CONCLUSION
This investigation uncovered an inverse relationship between the serum Klotho levels and diabetic kidney disease. To further authenticate these findings, additional randomized controlled trials are essential, as they suggest a robust negative correlation between Klotho levels and DKD.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-025-01623-7.
目的
本研究旨在阐明美国成年糖尿病患者血清α-klotho水平与糖尿病肾病（DKD）之间的联系。
方法
使用2007 - 2016年美国国家健康与营养检查调查（NHANES）的数据，通过多变量线性回归模型探讨α-klotho水平与糖尿病肾病（DKD）风险之间的相关性。进行平滑曲线拟合以发现潜在的非线性关系。随后，利用全基因组关联研究（GWAS）的汇总统计数据进行两样本孟德尔随机化（MR）分析。采用的主要方法是逆方差加权（IVW），并辅以其他MR技术来研究α-klotho水平与糖尿病肾病（DKD）之间的因果关系。此外，进行敏感性分析以评估研究结果的稳健性。
结果
横断面研究纳入了NHANES中总共3214例糖尿病患者，其中1967例参与者被诊断为糖尿病肾病（DKD）。多变量逻辑回归模型显示，α-klotho水平越高，DKD的发病率越低。MR结果表明血清α-klotho浓度是糖尿病肾病的直接保护因素（IVW比值比（OR）：0.859（95%置信区间0.740 - 0.998），P<0.05），这与NHANES观察性研究的结论一致。
结论
本研究发现血清α-klotho水平与糖尿病肾病之间存在负相关关系。由于这些结果表明α-klotho水平与DKD之间存在强烈的负相关，因此需要进一步的随机对照试验来验证这些发现。
补充信息
在线版本包含可在10.1007/s40200 - 025 - 01623 - 7获取的补充材料。
Zotero 插件