Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pediatric Endocrinology, Istanbul, Turkey.
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department Metabolic Diseases and Nutrition, Istanbul, Turkey.
J Pharm Biomed Anal. 2024 Jun 15;243:116072. doi: 10.1016/j.jpba.2024.116072. Epub 2024 Feb 27.
Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be used as biomarkers in the evaluation of oxidative stress. In this study, our aim is to compare the concentrations of serum and urinary pteridine derivatives, as well as serum IDO activity, in children and adolescents diagnosed with T1D and those in a healthy control group.
A cross-sectional study was performed and included 93 patients with T1D and 71 healthy children. Serum and urine biopterin, neopterin, monapterin, pterin, isoxanthopterin, and pterin-6-carboxylic acid (6PTC) and serum tryptophan and kynurenine levels were analyzed and compared with healthy controls. High-performance liquid chromatography was used for the analysis of pteridine derivatives, tryptophan, and kynurenine. Xanthine oxidase (XO) activity, a marker of oxidative stress, was defined by measurement of serum and urine isoxanthopterin. As an indicator of indolamine 2,3-dioxygenase (IDO) activity, the ratio of serum kynurenine/tryptophan was used.
Serum isoxanthopterin and tryptophan concentrations were increased, and serum 6PTC concentration was decreased in children with T1D (p=0.01, p=0.021, p<0.001, respectively). In children with T1D, IDO activity was not different from healthy controls (p>0.05). Serum neopterin level and duration of diabetes were weakly correlated (p=0.045, r=0.209); urine neopterin/creatinine and isoxanthopterin/creatinine levels were weakly correlated with HbA1c levels (p=0.005, r=0.305; p=0.021, r=0.249, respectively). Urine pterin/creatinine level negatively correlated with body mass index-SDS. (p=0.015, r=-0.208).
We found for the first time that isoxanthopterin levels increased and 6PTC levels decreased in children and adolescents with T1D. Elevated isoxanthopterin levels suggest that the XO activity is increased in TID. Increased XO activity may be an indicator of vascular complications reflecting T1D-related endothelial dysfunction.
1 型糖尿病（T1D）及其并发症已知与氧化应激有关。蝶呤衍生物和色氨酸 2,3-双加氧酶（IDO）活性可作为评估氧化应激的生物标志物。本研究旨在比较诊断为 T1D 的儿童和青少年与健康对照组之间血清和尿液蝶呤衍生物以及血清 IDO 活性的浓度。
进行了一项横断面研究，纳入了 93 名 T1D 患者和 71 名健康儿童。分析并比较了血清和尿液中二氢生物蝶呤、新蝶呤、单蝶呤、蝶呤、异黄质、蝶呤-6-羧酸（6PTC）和血清色氨酸、犬尿氨酸水平。采用高效液相色谱法分析蝶呤衍生物、色氨酸和犬尿氨酸。黄嘌呤氧化酶（XO）活性作为氧化应激的标志物，通过测量血清和尿液异黄质来定义。血清犬尿氨酸/色氨酸比值作为 IDO 活性的指标。
T1D 患儿血清异黄质和色氨酸浓度升高，血清 6PTC 浓度降低（p=0.01，p=0.021，p<0.001）。T1D 患儿 IDO 活性与健康对照组无差异（p>0.05）。血清新蝶呤水平与糖尿病病程呈弱相关（p=0.045，r=0.209）；尿液新蝶呤/肌酐和异黄质/肌酐水平与 HbA1c 水平呈弱相关（p=0.005，r=0.305；p=0.021，r=0.249）。尿蝶呤/肌酐水平与体重指数-SDS 呈负相关（p=0.015，r=-0.208）。
我们首次发现 T1D 患儿和青少年血清异黄质水平升高，6PTC 水平降低。异黄质水平升高提示 TID 中 XO 活性增加。XO 活性增加可能是反映 T1D 相关内皮功能障碍的血管并发症的指标。
