P.034 The Influence of Gender, Cyclooxygenase-2 Inhibition, and Hyperglycemia on Vascular Function in Uncomplicated type 1 Diabetes Mellitus

Abstract

Purpose

We have previously shown that young women vs. men with uncomplicated type 1 diabetes mellitus (DM-1) exhibit a deleterious renal vasoconstrictive response to clamped hyperglycemia. Since the cyclooxyge-nase-2 (COX2) system has important systemic hemodynamic effects in DM-1 and is activated by hyperglycemia, we hypothesized we would find a similar gender-based systemic vascular response to selective COX2 inhibition and accentuation during clamped hyperglycemia.

Methods

Outpatient ambulatory blood pressure monitoring and inpatient vascular function assessment (applanation tonometry and brachial artery reactivity) during clamped euglycemia and hyperglycemia were assessed before and after COX2 inhibition (celecoxib 200mg daily for 14 days).

Results

Before COX2 inhibition, women [n = 9] vs. men [n = 12] with DM-1 exhibited a lower ambulatory systolic BP (114 ± 3 vs. 124 ± 3mmHg, p = 0.029), which was no longer present after COX2 inhibition. Radial augmentation index was higher before (euglycemia 11.5 ± 4.2 vs. 0.8 ± 3.1%, p = 0.048; hyperglycemia 10.8 ± 4.5 vs. -3.1 ± 3.6%, p = 0.024) and after COX2 inhibition (euglycemia 13.1 ± 2.3 vs. -1.3 ± 3.5%, p = 0.005; hyperglycemia 9.1 ± 2.7 vs. 1.1 ± 4.0%%, p = 0.045). No differences in pulse wave velocity were detected. Endothelial-dependent FMD responses were also not different, but endothelial-independent GTN response was higher before (euglycemia 14.0 ± 0.2 vs. 10.8 ± 1.0%, p = 0.045; hyperglycemia 16.6 ± 2.3 vs. 11.5 ± 1.1%, p = 0.045) and then no different after COX2 inhibition.

Conclusions

COX2 inhibition in women with DM-1 results in a loss of gender-based systolic BP protection. Increased augmentation index in women with DM-1 does not appear to be COX2 mediated or acutely affected by hyperglycemia. Endothelial-independent vascular smooth muscle response in women may be sensitive to COX2 inhibition and warrants further investigation.