Renal hyperfiltration is a determinant of endothelial function responses to cyclooxygenase 2 inhibition in type 1 diabetes

Abstract

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 m2, n = 13) or normofiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, 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. © 2010 by the American Diabetes Association.