代谢组学研究揭示并验证了两个中国2型糖尿病数据集里糖尿病视网膜病变的潜在生物标志物：一项横断面研究。

Metabolomic studies reveal and validate potential biomarkers of diabetic retinopathy in two Chinese datasets with type 2 diabetes: a cross-sectional study.

作者信息

Zhou Xingchen, Hou Guixue, Wang Xin, Peng Zhaoyi, Yin Xiaoming, Yang Jing, Wang Shan, He Yayi, Wang Yue, Sui Jing, Qiang Wei, Guo Hui, Wang Yanan, Lin Liang, Shi Bingyin, He Mingqian

机构信息

Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, No.277, West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.

BGI-SHENZHEN, Building NO.7, BGI Park, No. 21 Hongan 3rd Street, Yantian District, Shenzhen, Guangdong, 518083, People's Republic of China.

出版信息

Cardiovasc Diabetol. 2024 Dec 18;23(1):439. doi: 10.1186/s12933-024-02535-1.

DOI:10.1186/s12933-024-02535-1

PMID:39696333

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11657842/

Abstract

BACKGROUND

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and causes vision impairment and blindness. The presence of major risk factors for DR, such as high levels of HbA1c, does not predict all DR pathogenesis in the clinic, which suggests that uncovering the underlying mechanisms and identifying novel markers are needed. Previous evidence has shown that the serum metabolic signature of DR is unique and detectable compared with that of diabetes mellitus (DM). Here, we aimed to identify serum metabolites as reliable biomarkers for the presence of DR in type 2 DM (T2DM) patients.

METHODS

We performed untargeted and targeted metabolomic studies using liquid chromatography‒mass spectrometry (LC‒MS) and multiple reaction monitoring (MRM) methods on the serum samples of T2DM patients. For the discovery dataset, 39 DR patients and 39 non-DR (NDR) patients were included. For the validation dataset, 95 DR patients and 95 non-DR (NDR) patients were included. Receiver operating characteristic curve analysis was performed to evaluate the discriminating power of the metabolites. Binary logistic regression models were fit to evaluate the associations of metabolite peak areas or neurotransmitter concentrations with the presence of DR and adjusted for known risk factors.

RESULTS

A total of 7123 metabolites were tested. The 39 DR patients had a mean age of 56 years with an average diabetes duration of 12 years, and the 39 NDR patients had a mean age of 57 years with an average diabetes duration of 11 years. Nine serum candidate markers were further identified. Six out of nine markers were associated with DR after we adjusted for covariates, including blood pressure, HbA1c, diabetes duration, fasting blood glucose, triglyceride, eGFR etc. Among them, eicosapentaenoic acid (EPA) and L-tyrosine were validated in an independent, risk factor-matched sample set. The serum L-tyrosine concentration was decreased in DR group by 47% (-0.22 ± 0.87 vs. 0.48 ± 1.05, P < 0.001), of which the cutoff value was 0.10 mg/ml, with 86% sensitivity and 40% specificity (AUC = 0.62, 95% CI = 0.54-0.70, P = 0.005).

CONCLUSIONS

Low levels of circulating L-Tyrosine indicate retinopathy occurrence in T2DM population.

摘要

背景

糖尿病视网膜病变（DR）是糖尿病的一种主要微血管并发症，可导致视力损害和失明。临床中，DR的主要危险因素（如糖化血红蛋白水平升高）的存在并不能预测所有DR的发病机制，这表明需要揭示其潜在机制并确定新的标志物。先前的证据表明，与糖尿病（DM）相比，DR的血清代谢特征是独特且可检测的。在此，我们旨在确定血清代谢物作为2型糖尿病（T2DM）患者DR存在的可靠生物标志物。

方法

我们使用液相色谱-质谱联用（LC-MS）和多反应监测（MRM）方法对T2DM患者的血清样本进行了非靶向和靶向代谢组学研究。对于发现数据集，纳入了39例DR患者和39例非DR（NDR）患者。对于验证数据集，纳入了95例DR患者和95例非DR（NDR）患者。进行受试者工作特征曲线分析以评估代谢物的鉴别能力。拟合二元逻辑回归模型以评估代谢物峰面积或神经递质浓度与DR存在之间的关联，并对已知危险因素进行校正。

结果

共检测了7123种代谢物。39例DR患者的平均年龄为56岁，平均糖尿病病程为12年，39例NDR患者的平均年龄为57岁，平均糖尿病病程为11年。进一步确定了9种血清候选标志物。在我们对协变量（包括血压、糖化血红蛋白、糖尿病病程、空腹血糖、甘油三酯、估算肾小球滤过率等）进行校正后，9种标志物中有6种与DR相关。其中，二十碳五烯酸（EPA）和L-酪氨酸在一个独立的、与危险因素匹配的样本集中得到验证。DR组血清L-酪氨酸浓度降低了47%（-0.22±0.87对0.48±1.05，P<0.001），其截断值为0.10mg/ml，敏感性为86%，特异性为40%（AUC=0.62，95%CI=0.54-0.70，P=0.005）。