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

• Published in: Diabetes care Vol. 33; no. 6; pp. 1344 - 1346
• Main Authors: Cherney, David Z.I, Miller, Judith A, Scholey, James W, Nasrallah, Rania, Hébert, Richard L, Dekker, Maria G, Slorach, Cameron, Sochett, Etienne B, Bradley, Timothy J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2010
• Subjects: Adolescent; Adult; analysis of variance; Biological and medical sciences; Blood pressure; Celecoxib; COX-2 inhibitors; Cyclooxygenase 2 Inhibitors; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; drug effects; drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; filtration; foot-and-mouth disease; glomerular filtration rate; Glomerular Filtration Rate - drug effects; Humans; Hyperglycemia; insulin-dependent diabetes mellitus; Kidney; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Male; Medical sciences; Metabolic diseases; Miscellaneous; Original Research; pathology; pharmacology; physiopathology; prostaglandin synthase; Public health. Hygiene; Public health. Hygiene-occupational medicine; Pyrazoles; Pyrazoles - therapeutic use; Rodents; Sample size; Studies; Sulfonamides; Sulfonamides - therapeutic use; therapeutic use; Type 1 diabetes; Veins & arteries; Young Adult; Canada; Endocrinopathy; Human; Immunopathology; Endothelial cell; Nutrition; Enzyme; Cyclooxygenase 2; Determinant; Cyclooxygenase 1; Autoimmune disease; Metabolic diseases; Kidney; Endothelium; Urinary system; Type 1 diabetes; Inhibitor; Oxidoreductases; Inhibition; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc09-2340

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.