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 >or=135 ml/min/1.73 m(2), n = 13) or normofiltration (glomerular filtration rate >or=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.