Insulin resistance as the major determinant of endothelial dysfunction in morbidily obese Qataris

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 649-677-Adipocyte Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-667
Nelson Ndubuisi Orie*1, Aysha Ahmad Bakhamis2, Marshal Al-Jaber2, Mohamed Al Emadi3, Samer Rida3, Mohammed Alsayrafi2 and Vidya Mohamed-Ali2
1ADL Qatar, Doha, Qatar, 2Anti Doping Lab Qatar, Doha, Qatar, 3Al Emadi Hospital, Doha, Qatar
Background & objectives: Endothelial dysfunction is a known risk factor for vascular disease in obesity. With the incidence of obesity in the middle east at all-time high, proper management of associated cardiovascular complications will benefit from better understanding of the vascular impact of the expanding fat. Such impact can be made worse by increasing insulin resistance (IR). It is, however, unclear how severe the impact would be on a relatively young obese population. This study investigated the impact of insulin resistance on endothelium-dependent relaxation of small vessels from IR compared with insulin-sensitive (IS) obese and relatively young Qataris.

Methods: Arteries were isolated from omental (OM) and subcutaneous (SC) adipose tissues collected from consented Qatari patients (average age 32 years) undergoing bariatric surgery for weight loss. The arteries (ID ~250 µm for SC and ~ 240 µm for OM) were cut into segments (~2 mm) and mounted on a dual wire Myograph (510A) for measurement of isometric tension. Cumulative concentration-response curves were constructed for acetylcholine (1- 30000 nM, the classical endothelium-dependent relaxant) in the absence or presence of Nω-Nitro-L-arginine methyl ester (L-NAME,100 µM, a nitric oxide [NO] synthase inhibitor) on initial tone generated with noradrenaline (5 µM). Relaxation to sodium nitroprusside (SNP, an endothelium-independent NO donor) and prostaglandin E2 were also recorded.

Results: The mean body mass index of the patients was 43 Kg.m-2 and their blood glucose 5.6 mmol/L. Insulin levels were 19 vs 3 µU/ml for IR vs IS patients and their indices of insulin resistance (HOMA) were 5 vs 1 respectively.

Maximum relaxation to Ach was significantly reduced in OM vessels from IR patients (Emax 37±4 %) but not in IS patients compared with SC vessels (Emax 79±4 %, p<0.001) from same patients. In contrast, the relaxation to SNP and PGE2 in the IR patients were greater in OM vessels compared with the SC vessels. L-NAME caused further shift to the right of the Ach curve.

Conclusions: These results suggest that insulin resistance is the major determinant of altered endothelial physiology in morbidly obese Qataris. The data also demonstrate that early changes in endothelial vasomotor function are depot-specific with more marked impact on OM compared with SC vessels of insulin-resistant Qataris.

Nothing to Disclose: NNO, AAB, MA, MA, SR, MA, VM

*Please take note of The Endocrine Society's News Embargo Policy at