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基于核磁共振的脂质组学在1型糖尿病心血管代谢风险评估中的应用:一项探索性分析

Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis.

作者信息

Serés-Noriega Tonet, Ortega Emilio, Perea Verónica, Giménez Marga, Boswell Laura, Mariaca Karla, Font Carla, Mesa Alex, Viñals Clara, Blanco Jesús, Vinagre Irene, Pané Adriana, Esmatjes Enric, Conget Ignacio, Amor Antonio J

机构信息

Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain.

Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

出版信息

Diabetes Ther. 2023 Mar;14(3):553-567. doi: 10.1007/s13300-023-01372-x. Epub 2023 Feb 3.

Abstract

INTRODUCTION

Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk.

METHODS

We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by H NMR. Bivariate and multivariate-adjusted differences in H NMR lipidomics were evaluated.

RESULTS

We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both).

CONCLUSION

In our preliminary study of individuals with T1D at high risk, several H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.

摘要

引言

心血管疾病(CVD)是1型糖尿病(T1D)患者死亡的主要原因。然而,需要用于识别更易发生这些事件的个体的日常实践工具。我们旨在评估基于核磁共振(H NMR)的脂质组学分析与高危T1D个体的几种CVD风险变量(包括临床前期颈动脉粥样硬化)之间的关系。

方法

我们纳入了无CVD的T1D患者,这些患者至少具备以下一项:年龄≥40岁、糖尿病肾病或合并另一个风险因素病程≥10年。通过标准化超声检查方案确定斑块的存在(内膜中层厚度>1.5 mm)。通过H NMR进行脂质组学分析。评估H NMR脂质组学的双变量和多变量调整差异。

结果

我们纳入了n = 131名参与者(49.6%为女性,年龄46.4±10.3岁,糖尿病病程27.0±9.5年,47.3%使用他汀类药物)。28.2%的个体存在颈动脉斑块(n = 12,有≥3个斑块)。血糖(糖化血红蛋白)、人体测量学指标(体重指数和腰围)以及胰岛素抵抗相关指标(脂肪肝指数和估计的葡萄糖处置率)是与H NMR衍生的脂质组学分析最相关的变量(所有p < 0.01)。关于临床前期动脉粥样硬化,即使在调整年龄、性别、高血压、他汀类药物使用、平均5年糖化血红蛋白和糖尿病病程后,鞘磷脂仍与颈动脉斑块的存在独立相关(每增加0.1 mmol/L,比值比为0.50 [0.28 - 0.86];p = 0.013)。此外,在多变量模型中,亚油酸和ω-6脂肪酸仍与更高的斑块负荷(≥3个斑块)独立相关(分别为0.17 [0.03 - 0.93]和0.27 [0.07 - 0.97];两者p < 0.05)。

结论

在我们对高危T1D个体的初步研究中,几个H NMR衍生的脂质组学参数与临床前期动脉粥样硬化独立相关。具体而言,ω-6脂肪酸和亚油酸在识别斑块负荷较高的个体方面似乎很有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b0/9981843/107ab5c6b3a5/13300_2023_1372_Fig1_HTML.jpg

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