Hypoglycemia, but Not Glucose Variability, Relates to Vascular Function in Children with Type 1 Diabetes

Abstract

<h4>Background</h4>Chronic sustained hyperglycemia unequivocally predicts vascular disease in diabetes. However, the vascular risk of glucose variability, including hypoglycemia, is uncertain. Vascular dysfunction is present in children with type 1 diabetes and is a critical precursor of atherosclerosis. We aimed to evaluate the relationship between glucose variability and vascular function in children with type 1 diabetes.<h4>Subjects and methods</h4>Fifty-two type 1 diabetes subjects (14 [SD 2.7] years old, 25 males) had continuous glucose monitoring that included 48 h of data used to evaluate glucose variability (mean amplitude of glycemic excursions [MAGE] and other measurements) and hypoglycemia indices (glycemic risk assessment diabetes equation [GRADE] hypoglycemia, Low Blood Glucose Index [LBGI], and observed duration of hypoglycemia). Children with type 1 diabetes and 50 age- and gender-matched controls had assessments of vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation [GTN]).<h4>Results</h4>Children with type 1 diabetes had lower FMD and GTN than controls (P=0.02 and P<0.001, respectively). GRADE hypoglycemia and LBGI were inversely related to FMD (r=-0.36, P=0.009 and r=-0.302, P=0.03, respectively) but did not relate to GTN. GRADE hypoglycemia was independently related to FMD (regression coefficient=-0.25±0.09, P=0.006). MAGE and other measurements of glucose variability measurements did not relate to FMD or GTN.<h4>Conclusions</h4>Hypoglycemia, but not glucose variability, during continuous glucose monitoring relates to impaired vascular endothelial function in children with type 1 diabetes. Hypoglycemia may be an additional risk factor for early cardiovascular disease, but the effect of glucose variability, independent of glycosylated hemoglobin, on vascular function remains uncertain.