School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Endocrine. 2024 May;84(2):328-344. doi: 10.1007/s12020-023-03598-y. Epub 2023 Nov 23.
Novel biomarkers have been suggested for the diagnosis and prognosis of diabetes mellitus. The biomarker utility of netrin-1 in diabetes as an extracellular protein has been investigated. In this systematic review and meta-analysis, we reviewed the role of netrin-1 as a biomarker in prediabetes, diabetes, and complications of diabetes.
PubMed, Embase, Scopus, and Web of Science were systematically searched for studies that measured circulatory and/or urinary netrin-1 levels in diabetes and compared them with non-diabetic patients or evaluated the prognostic role of this marker. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using random-effect meta-analysis to compare netrin-1 levels between groups. The impact of mean age, male sex percentage, sample size, mean body mass index, and publication year on the overall heterogeneity was assessed using meta-regression.
Among 413 records from international databases, 19 original studies were included with 2061 cases (1137 diabetics, 196 prediabetics, and 728 healthy controls). Meta-analysis of eight studies measuring netrin-1 in patients with diabetes and comparing it with healthy controls showed no significant difference between the two groups (SMD 0.69, 95% CI -0.78 to 2.16, I = 98%, p-value = 0.36). On the other hand, a meta-analysis of netrin-1 levels in patients with prediabetes in comparison with healthy controls revealed that they had lower levels (SMD -0.51, 95% CI -0.81 to -0.21, p-value < 0.01). Diabetic patients with microalbuminuria and macroalbuminuria had significantly higher circulatory netrin-1 levels compared to normoalbuminuric group SMD 1.18, 95% CI 0.83 to 1.53, p-value < 0.01 and SMD 1.67, 95% CI 0.76 to 2.58, p-value < 0.01, respectively). Moreover, no difference in urinary netrin-1 levels was found between micro-, macro-, and normoalbuminuric groups (p-value > 0.05).
Netrin-1 showed promising results as a biomarker in diabetes prognosis. However, more studies are required to confirm our findings, and higher sample size studies are needed to evaluate the diagnostic utility of this marker.
新的生物标志物已被提出用于诊断和预测糖尿病。神经导向因子 1 作为一种细胞外蛋白，其在糖尿病中的诊断价值已被研究。在本系统评价和荟萃分析中，我们综述了神经导向因子 1 作为糖尿病及其并发症的预测生物标志物的作用。
我们系统性地检索了 PubMed、Embase、Scopus 和 Web of Science 中评估循环和/或尿液神经导向因子 1 水平在糖尿病及其并发症中的诊断和预后价值的研究，并将糖尿病患者与非糖尿病患者进行比较。使用随机效应荟萃分析计算标准化均数差值（SMD）和 95%置信区间（CI）来比较组间神经导向因子 1 水平。使用 meta 回归评估平均年龄、男性百分比、样本量、平均体重指数和发表年份对总体异质性的影响。
从国际数据库的 413 条记录中，纳入了 19 项原始研究，共纳入 2061 例患者（1137 例糖尿病患者、196 例糖尿病前期患者和 728 例健康对照者）。对 8 项研究进行荟萃分析，评估糖尿病患者与健康对照者之间的神经导向因子 1 水平，结果显示两组间无显著差异（SMD 0.69，95% CI -0.78 至 2.16，I = 98%，p 值 = 0.36）。另一方面，对糖尿病前期患者与健康对照者的神经导向因子 1 水平进行荟萃分析显示，前者的水平较低（SMD -0.51，95% CI -0.81 至 -0.21，p 值 < 0.01）。与正常白蛋白尿组相比，微量白蛋白尿和大量白蛋白尿的糖尿病患者的循环神经导向因子 1 水平显著升高（SMD 1.18，95% CI 0.83 至 1.53，p 值 < 0.01 和 SMD 1.67，95% CI 0.76 至 2.58，p 值 < 0.01）。此外，微量白蛋白尿、大量白蛋白尿和正常白蛋白尿组之间的尿神经导向因子 1 水平无差异（p 值 > 0.05）。
神经导向因子 1 作为糖尿病预后的生物标志物具有较好的预测价值。然而，需要更多的研究来证实我们的发现，并且需要更大的样本量研究来评估该标志物的诊断价值。
