Aix-Marseille University, INSERM, INRAE, C2VN, 13005 Marseille, France.
Aix-Marseille University, INSERM, INRAE, C2VN, BIOMET Aix-Marseille Technology Platform, 13005 Marseille, France.
Int J Mol Sci. 2023 Jul 27;24(15):12053. doi: 10.3390/ijms241512053.
Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) which is the main cause of vision loss in the working-age population. Currently known risk factors such as age, disease duration, and hemoglobin A1c lack sufficient efficiency to distinguish patients with early stages of DR. A total of 194 plasma samples were collected from patients with type 2 DM and DR (moderate to proliferative (PDR) or control (no or mild DR) matched for age, gender, diabetes duration, HbA1c, and hypertension. Untargeted lipidomic and metabolomic approaches were performed. Partial-least square methods were used to analyze the datasets. Levels of 69 metabolites and 85 lipid species were found to be significantly different in the plasma of DR patients versus controls. Metabolite set enrichment analysis indicated that pathways such as metabolism of branched-chain amino acids (methylglutaryl carnitine = 0.004), the kynurenine pathway (tryptophan < 0.001), and microbiota metabolism (p-Cresol sulfate = 0.004) were among the most enriched deregulated pathways in the DR group. Moreover, Glucose-6-phosphate ( = 0.001) and N-methyl-glutamate ( < 0.001) were upregulated in DR. Subgroup analyses identified a specific signature associated with PDR, macular oedema, and DR associated with chronic kidney disease. Phosphatidylcholines (PCs) were dysregulated, with an increase of alkyl-PCs (PC O-42:5 < 0.001) in DR, while non-ether PCs (PC 14:0-16:1, < 0.001; PC 18:2-14:0, < 0.001) were decreased in the DR group. Through an unbiased multiomics approach, we identified metabolites and lipid species that interestingly discriminate patients with or without DR. These features could be a research basis to identify new potential plasma biomarkers to promote 3P medicine.
糖尿病视网膜病变（DR）是糖尿病（DM）的一种微血管并发症，是工作年龄段人群视力丧失的主要原因。目前已知的危险因素，如年龄、疾病持续时间和糖化血红蛋白（HbA1c），在区分 DR 早期患者方面效率不足。共收集了 194 例 2 型糖尿病（DM）和 DR 患者（中度至增生性（PDR）或对照（无或轻度 DR）的血浆样本，这些患者在年龄、性别、糖尿病持续时间、HbA1c 和高血压方面相匹配。采用非靶向脂质组学和代谢组学方法进行分析。使用偏最小二乘法（PLS）对数据集进行分析。结果发现，DR 患者与对照组相比，血浆中有 69 种代谢物和 85 种脂质种类的水平有显著差异。代谢物集富集分析表明，支链氨基酸代谢（甲基戊二酰肉碱， = 0.004）、犬尿氨酸途径（色氨酸， < 0.001）和微生物群代谢（对-羟苯硫酸， = 0.004）等途径在 DR 组中最为丰富。此外，DR 组中葡萄糖-6-磷酸（ = 0.001）和 N-甲基-谷氨酸（ < 0.001）上调。亚组分析确定了与 PDR、黄斑水肿和与慢性肾病相关的 DR 相关的特定特征。磷酸胆碱（PCs）发生失调，DR 中烷基-PCs（PC O-42：5 < 0.001）增加，而非醚 PC（PC 14：0-16：1， < 0.001；PC 18：2-14：0， < 0.001）减少。通过一种无偏的多组学方法，我们鉴定出了可区分 DR 患者和非 DR 患者的代谢物和脂质种类。这些特征可以作为识别新的潜在血浆生物标志物的研究基础，以促进 3P 医学的发展。
