Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes.
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/m(2)) premenopausal nondiabetic women with a history of gestational diabetes.


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.
Bergholm
Robert
R
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland.
Tiikkainen
Mirja
M
Vehkavaara
Satu
S
Tamminen
Marjo
M
Teramo
Kari
K
Rissanen
Aila
A
Yki-Järvinen
Hannele
H
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D008078:Cholesterol, LDL / Q000097:blood*; D016640:Diabetes, Gestational; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007783:Lactones / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy*; D000077403:Orlistat; D010919:Placebos; D011247:Pregnancy; D014664:Vasodilation / Q000187:drug effects*; D015431:Weight Loss
D019440:Anti-Obesity Agents; D008078:Cholesterol, LDL; D007783:Lactones; D010919:Placebos; D000077403:Orlistat