Renal Hyperfiltration Is a Determinant of Endothelial Function Responses to Cyclooxygenase 2 Inhibition in Type 1 Diabetes

OBJECTIVE - Our aim was to examine the effect of cyclooxygenase 2 (COX2) inhibition on endothelial function in subjects with type 1 diabetes analyzed on the basis of renal filtration status. RESEARCH DESIGN AND METHODS - Flow-mediated dilation (FMD) was determined in type 1 diabetic subjects and hyperfiltration (glomerular filtration rate >= 135 ml/min/1.73 m(2), n = 13) or normofiltration (glomerular filtration rate >= 135 ml/min/1.73 m(2), n = 11). Studies were performed before and after celecoxib (200 mg daily for 14 days) during euglycemia and hyperglycemia. RESULTS - Baseline parameters were similar in the two groups. Pretreatment, FMD was augmented in normofiltering versus hyperfiltering subjects during clamped euglycemia (10.2 +/- 5.3% vs. 5.9 +/- 2.3%, P = 0.003). COX2 inhibition suppressed FMD in normofiltering (10.2 +/- 5.3% to 5.8 +/- 3.4%, P = 0.006) versus hyperfiltering subjects (ANOVA interaction, P = 0.003). CONCLUSIONS - Systemic hemodynamic function, including the response to COX2 inhibition, is related to filtration status in diabetic subjects and may reflect general endothelial dysfunction.