Pteridine and tryptophan pathways in children with type 1 diabetes: Isoxanthopterin as an indicator of endothelial
Yavuz Özer1, Mehmet Şerif Cansever2, Hande Turan1
1Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pediatric Endocrinology, Istanbul, Turkey.
Insights
Type 1 diabetes (T1D) is linked to oxidative stress. This study found increased isoxanthopterin and decreased 6PTC levels in children with T1D, suggesting elevated xanthine oxidase activity and potential vascular complications.
Area of Science:
- Biochemistry
- Pediatric Endocrinology
- Oxidative Stress Research
Background:
- Type 1 diabetes (T1D) is associated with increased oxidative stress.
- Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity are potential biomarkers for oxidative stress.
- Evaluating these biomarkers in pediatric T1D populations is crucial for understanding disease mechanisms.
Purpose of the Study:
- To compare serum and urinary pteridine derivatives and serum IDO activity in children and adolescents with T1D versus healthy controls.
- To investigate the relationship between these biomarkers and clinical parameters in T1D.
- To identify novel oxidative stress markers in pediatric T1D.
Main Methods:
- Cross-sectional study involving 93 T1D patients and 71 healthy children.
- Analysis of serum and urine pteridine derivatives (biopterin, neopterin, monapterin, pterin, isoxanthopterin, 6PTC) using high-performance liquid chromatography.
- Assessment of IDO activity via serum kynurenine/tryptophan ratio and xanthine oxidase (XO) activity via isoxanthopterin levels.
Main Results:
- Children with T1D showed increased serum isoxanthopterin and tryptophan, and decreased serum 6PTC.
- IDO activity did not differ significantly between T1D patients and controls.
- Elevated urine neopterin/creatinine and isoxanthopterin/creatinine correlated with HbA1c; urine pterin/creatinine negatively correlated with BMI-SDS.
Conclusions:
- Isoxanthopterin levels are elevated, and 6PTC levels are decreased in pediatric T1D for the first time.
- Increased isoxanthopterin suggests elevated XO activity in T1D.
- Elevated XO activity may indicate vascular complications and endothelial dysfunction in T1D.
Aim:
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.
Method:
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.
Results:
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).
Conclusion:
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.
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