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

BACKGROUND: 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. SUBJECTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.