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Endothelial Dysfunction Relates to Folate Status in Children and Adolescents With Type 1 Diabetes

¹ Department of Paediatrics, Wellington School of Medicine and Health Sciences, Wellington, New Zealand
² Department of Ultrasonography, Women’s and Children’s Hospital, Adelaide, Australia
³ Public Health Research Unit, Women’s and Children’s Hospital, Adelaide, Australia
⁴ Department of Diabetes and Endocrinology, Women’s and Children’s Hospital, Adelaide, Australia
⁵ Department of Clinical Pathology, Women’s and Children’s Hospital, Adelaide, Australia
⁶ Department of Paediatrics, University of Adelaide, Adelaide, Australia

Endothelial dysfunction occurs early in the development of vascular disease in diabetes. Total plasma homocyst(e)ine (tHcy) is associated with endothelial dysfunction. We therefore aimed to assess endothelial function in children with type 1 diabetes in relation to tHcy and its determinants. Endothelial function was assessed in 36 children with type 1 diabetes aged 13.7 ± 2.2 years and 20 age- and sex-matched control subjects using ultrasound assessment of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-dependent brachial artery responses. von Willebrand factor (vWF) and thrombomodulin, markers of endothelial activation, were measured in 64 children with type 1 diabetes and 52 control subjects. Fasting glucose, tHcy, serum and red cell folate, vitamin B12, HbA_1c, creatinine, and lipids were also measured. FMD (5.2 ± 4.7 vs. 9.1 ± 4.0%, P = 0.002) and the ratio of FMD:GTN-induced dilatation (0.22 ± 0.39 vs. 0.41 ± 0.29%, P = 0.008) were significantly lower in diabetic subjects, indicating endothelial dysfunction. In diabetic subjects, red cell folate correlated independently with FMD (ß = 0.42, P = 0.028) and the ratio of FMD:GTN-induced dilatation (ß = 0.59, P < 0.001). Resting vessel diameter correlated independently with tHcy (ß = -0.51, P < 0.001) and height (ß = 0.65, P < 0.001). vWF correlated independently with HbA_1c (ß = 0.38, P = 0.003), and thrombomodulin correlated independently with red cell folate (ß = -0.38, P = 0.005), tHcy (ß = -0.37, P = 0.004), diastolic blood pressure (ß = -0.28, P = 0.025), and creatinine clearance (ß = 0.26, P = 0.033). Children with type 1 diabetes have early endothelial dysfunction. Better folate status is associated with better endothelial function, as measured by higher FMD, higher FMD:GTN ratio, and lower thrombomodulin. Folate may therefore protect against endothelial dysfunction in children with diabetes.

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