Endothelial dysfunction (ED) is an impairment of endothelium-dependent vasorelaxation due to a loss of nitric oxide (NO) bioactivity in the vessel wall. it is considered an early functional change preceding atherosclerosis. Obesity is also associated with ED, however, the exact cause of ED in obesity is unknown. The effect of weight loss on endothelium-dependent and -independent vasodilatory responses has not been studied. Orlistat, a lipase inhibitor that prevents fat absorption and prevents weight loss, also lowers LDL cholesterol more than expected from weight loss alone. This fact may be beneficial for vascular function because lowering of LDL cholesterol with statins improves endothelial function.
Recently, investigators compared the effects of moderate weight loss with or without simultaneous lowering of fat absorption and LDL cholesterol on endothelial function in obese women. This investigator-initiated, double-blind, placebo-controlled study was designed to achieve an 8% body weight loss both in a group of women receiving orlistat and in another group receiving placebo. The subjects had to fulfill the following inclusion criteria: 1) previous gestational diabetes mellitus; 2) current age 20 to 50 years; 3) current BMI between 28 and 35 kg/[m.sup.2]; and 4) no known acute or chronic disease. A total of 57 women fulfilled the criteria and participated in the following tests before and after weight loss: 1) assessment of in vivo endothelial function; 2) measurement of forearm composition by magnetic resonance imaging (MRI); and 3) measurement of circulating markers of glucose and lipid metabolism.
After baseline testing, the subjects were randomized to receive either orlistat 120 mg three times daily or an identical looking placebo, both in addition to the prescribed hypocaloric diet. Following an 8% body weight reduction, subjects were placed on a weight-maintaining diet for at least two weeks before baseline measurements were collected. A total of 47 women achieved the weight loss goal and completed the study.
Vascular function was assessed in forearm resistance vessels by measuring forearm blood flow responses to intrabrachial artery infusions of endothelium-dependent (acetylcholine [Ach]) and -independent (sodium nitorprusside [SNP]) vasodilators.
The desired weight loss was achieved in both groups. Forearm and body compositions changed similarly in both groups. Responses to Ach increased by 41% to the low dose (5.9 [+ or -] 0.6 versus 8.3 4 [+ or -] 0.3 for flow in the experimental/ control arm, P lesser than 0.01) and by 33% to the high dose (7.6 4 [+ or -] 0.8 versus 10.1 [+ or -] 0.6, P lesser than 0.001) ion the orlistat group, but they remained unchanged in the placebo group. The blood flow responses to SNP did not differ significantly between the groups. LDL cholesterol decreased significantly in the orlistat group from 3.5 4. [+ or -] 0.2 to 3.0 [+ or -] 0.1 mmol/l (P lesser than 0.01) but remained unchanged in the placebo group. Within the orlistat group, the decrease in LDL cholesterol correlated significantly with the improvement in the blood flow response to Ach (r = -044, P lesser than 0.05).
Investigators conclude that orlistat, but not moderate weight loss alone, improves endothelial function in women with previous gestational diabetes. This observed improvement is also associated with a lowering of LDL cholesterol by orlistat.
R. Bergholm, M. Tiikkainen, S. Vehkavaara, et al. Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilation in obese women with previous gestational diabetes, Diabetes Care, (26:1667-1672, June, 2003). Correspondence: Hannele Yki-Jarvinen, MD, FRCP, PhD, Department of Medicine, Division of Diabetes, University of Helsinki, PO Box 340, FIN-00029 HUCH, Helsinki, Finland. E-mail: ykijarvi@helsinki.fi
COPYRIGHT 2003 Frost & Sullivan
COPYRIGHT 2003 Gale Group
Contact
Home
A
Methoxsalen