Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya, B2SLab, Barcelona, Spain.
Cardiovasc Diabetol. 2024 Mar 29;23(1):109. doi: 10.1186/s12933-024-02202-5.
In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state.
An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D.
A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D.
Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes.
在这项研究中，我们通过确定与糖尿病整体以及两性相关的脂质和与血糖状态相关的脂质，来评估 1 型糖尿病（T1D）和 2 型糖尿病（T2D）引起的脂质组改变。
对 360 名受试者（91 名 T1D、91 名 T2D、74 名糖尿病前期和 104 名对照（CT））进行非靶向脂质组学分析，以测量其脂质谱。采用超高效液相色谱-电喷雾电离质谱联用（UHPLC-ESI-MS）在正离子和负离子两种模式下进行。我们使用多元线性回归模型来（1）评估每个脂质特征与每种情况之间的关联，（2）确定与糖尿病相关的性别特异性差异，（3）通过考虑糖尿病前期阶段，确定与血糖状态相关的脂质。这些模型通过性别、年龄、高血压、血脂异常、体重指数、血糖、吸烟、收缩压、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、替代地中海饮食评分（aMED）和估计肾小球滤过率（eGFR）进行调整；在 T1D 和 T2D 之间的比较中，还包括糖尿病病程和糖化血红蛋白（HbA1c）。
共注释了来自 15 种独特脂质类别的 54 种独特脂质亚类。溶血磷脂酰胆碱（LPC）和神经酰胺（Cer）在 T1D 患者和 T2D 患者中的作用相反，LPC 在 T1D 中主要上调，在 T2D 中下调，而 Cer 在 T2D 中上调，在 T1D 中下调。此外，在 T1D 患者中，磷脂酰胆碱明显下调。关于性别特异性差异，由于性别，神经酰胺和磷脂酰胆碱表现出与糖尿病相关的重要差异。关于血糖状态，我们发现从正常血糖到糖尿病前期再到 T2D，一组 1-脱氧神经酰胺的水平逐渐升高。
我们的研究结果揭示了 T1D 和 T2D 中广泛的脂质代谢紊乱。此外，我们发现了与糖尿病相关的性别特异性脂质组变化，以及与血糖状态相关的脂质，这些脂质可能与糖尿病中已描述的分子机制有关。
