Mujammami Muhammad, Nimer Refat M, Al Mogren Maha, Almalki Reem, Alabdaljabar Mohamad S, Benabdelkamel Hicham, Abdel Rahman Anas M
Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia.
Diabetes University Center, King Saud University Medical City, King Saud University, Riyadh 12372, Saudi Arabia.
ACS Omega. 2024 Jul 17;9(30):32873-32880. doi: 10.1021/acsomega.4c03626. eCollection 2024 Jul 30.
The most prevalent comorbidity among cystic fibrosis (CF) patients is cystic fibrosis-related diabetes (CFRD). CFRD has been linked to one of the worse clinical outcomes and a higher mortality. Improved clinical results have been related to earlier diagnosis and treatment of CFRD. Therefore, the present study aimed to investigate the metabolome of human serum of patients with CFRD. This might aid in identifying novel biomarkers linked with the pathophysiology of CFRD and its diagnosis. The liquid chromatography-high-resolution mass spectrometry (LC-HRMS) metabolomics approach was utilized for serum samples from patients with CF ( = 36) and healthy controls ( = 36). Nine patients in the CF group had CFRD, and 27 were non-CFRD patients (nCFRD). A total of 2328 metabolites were significantly altered in CF compared with the healthy control. Among those, 799 significantly dysregulated metabolites were identified between CFRD and nCFRD. Arachidonic acid (AA), ascorbate, and aldarate metabolism were the most common metabolic pathways dysregulated in CF. l-Homocysteic acid (l-HCA) levels were significantly reduced in CF and CFRD compared to the control and nCFRD, respectively. In addition, gamma-glutamylglycine and l-5-hydroxytryptophan (5-HTP) had the highest discrimination between CFRD and nCFRD with AUC (0.716 and 0.683, respectively). These biomarkers might serve as diagnostic biomarkers and aid in understanding potential metabolic changes linked to CF and CFRD.
囊性纤维化(CF)患者中最常见的合并症是囊性纤维化相关糖尿病(CFRD)。CFRD与较差的临床结局之一及较高的死亡率相关。临床结果的改善与CFRD的早期诊断和治疗有关。因此,本研究旨在调查CFRD患者的人血清代谢组。这可能有助于识别与CFRD的病理生理学及其诊断相关的新型生物标志物。采用液相色谱-高分辨率质谱(LC-HRMS)代谢组学方法对CF患者(n = 36)和健康对照者(n = 36)的血清样本进行分析。CF组中有9例患者患有CFRD,27例为非CFRD患者(nCFRD)。与健康对照相比,CF患者共有2328种代谢物发生了显著变化。其中,在CFRD和nCFRD之间鉴定出799种显著失调的代谢物。花生四烯酸(AA)、抗坏血酸和醛糖代谢是CF中最常见的失调代谢途径。与对照组和nCFRD相比,CF组和CFRD组中的l-高半胱氨酸(l-HCA)水平分别显著降低。此外,γ-谷氨酰甘氨酸和l-5-羟色氨酸(5-HTP)在CFRD和nCFRD之间的鉴别能力最强,曲线下面积(AUC)分别为0.716和0.683。这些生物标志物可作为诊断生物标志物,并有助于理解与CF和CFRD相关的潜在代谢变化。