Lowering of LDL Cholesterol Rather Than Moderate Weight Loss Improves Endothelium-Dependent Vasodilatation in Obese Women With Previous Gestational Diabetes
- Robert Bergholm, MD1,
- Mirja Tiikkainen, MD1,
- Satu Vehkavaara, MD, PHD1,
- Marjo Tamminen, MD1,
- Kari Teramo, MD, PHD2,
- Aila Rissanen, MD, PHD3 and
- Hannele Yki-Järvinen, MD, FRCP, PHD1
- 1Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland
- 2Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
- 3Obesity Research Unit, University of Helsinki, Helsinki, Finland
Abstract
OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3–6 months, effects of orlistat (120 mg t.i.d., n = 23) and placebo (n = 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 ± 0.4 kg/m2) premenopausal nondiabetic women with a history of gestational diabetes.
RESEARCH DESIGN AND METHODS—Forearm blood flow responses to intra-arterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss.
RESULTS—Weight loss averaged 7.3 ± 0.2 kg (8.3 ± 0.1%) and 7.4 ± 0.2 kg (8.2 ± 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 ± 0.6 vs. 8.3 ± 0.3 for flow in the experimental/control arm, P < 0.01) and by 33% to the high dose (7.6 ± 0.8 vs. 10.1 ± 0.6, P < 0.001) in 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 ± 0.2 to 3.0 ± 0.1 mmol/l (P < 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 = −0.44, P < 0.05).
CONCLUSIONS—Orlistat but not moderate (8%) weight loss per se improves endothelial function in women with previous gestational diabetes. This improvement is associated with a lowering of LDL cholesterol by orlistat.
- ACh, acetylcholine
- GDM, gestational diabetes mellitus
- MRI, magnetic resonance imaging
- SNP, sodium nitroprusside
Footnotes
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Address correspondence and reprint requests to Hannele Yki-Järvinen, MD, FRCP, PhD, Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland. E-mail: ykijarvi{at}helsinki.fi.
Received for publication 29 November 2002 and accepted in revised form 2 January 2003.
A.R. is a member of the European scientific advisory board for the weight-reducing agent Xenical (orlistat), manufactured by Roche, and receives compensation for annual meetings.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
See accompanying editorial, p. 1927.
- DIABETES CARE
