Weight change and blood coagulability and fibrinolysis in healthy obese women.
OBJECTIVE
To study the effect of weight loss and subsequent weight maintenance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in obese women consuming a hypoenergetic, low-fat diet with or without orlistat. In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examined.


METHODS
Design-a 12-month randomized double-blind weight reduction trial of placebo and orlistat. Subjects-51 healthy obese women (age 44+/-0.7 y, BMI 36.2+/-0.5 kg/m(2), mean+/-s.e.m.) Treatment-the participants were on a hypoenergetic diet (-600 kcal daily). The diet was adjusted for actual body weight (-300 kcal) at 6 months. Women were randomized to receive either orlistat 120 mg three times daily (n=25) or placebo three times daily (n=26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements-changes of body weight, body composition, haemostatic and other cardiovascular risk factors were measured at 3-6 month intervals. The activity of plasma PAI-1 was measured by a chromogenic method, fibrinogen by the PT-derived method and the activity of FVII by the one-stage method.


RESULTS
The changes in body weight between orlistat and placebo groups were not statistically significantly different. Orlistat did not influence haemostatic factors beyond its effect on weight loss. Therefore, the results of the orlistat and placebo groups were pooled. The average weight loss at 3, 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively (P<0.001). Between 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen concentration were observed at any time point during the trial. During the first 3 months the activities of PAI-1 and FVII decreased. The decline depended on the magnitude of weight loss. Between months 6 and 12 the changes of PAI-1 and FVII activities paralleled the changes of body weight. The activities rose with weight rebound but remained below the 6-month values if weight loss was sustained or continued. The changes of serum insulin were significantly correlated with the changes of both PAI-1 and FVII at 6 months and with PAI-1 at 12 months.


CONCLUSIONS
The maintenance of modest weight loss is associated with long-term benefits in PAI-1 and FVII in obese women. The change of serum insulin is associated with the changes of PAI-1 activities. Fibrinogen is not affected by modest weight loss.
Rissanen
P
P
Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland, and Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland. paivi.risanen@hus.fi
Vahtera
E
E
Krusius
T
T
Uusitupa
M
M
Rissanen
A
A
D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000941:Antigens / Q000378:metabolism*; D001777:Blood Coagulation; D001835:Body Weight; D004038:Diet, Reducing; D005167:Factor VII / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen; D005342:Fibrinolysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007783:Lactones / Q000494:pharmacology*; D009765:Obesity / Q000097:blood* / Q000628:therapy*; D000077403:Orlistat; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*
D019440:Anti-Obesity Agents; D000941:Antigens; D007328:Insulin; D007783:Lactones; D017395:Plasminogen Activator Inhibitor 1; C042580:factor VII clotting antigen; D005167:Factor VII; D005340:Fibrinogen; D000077403:Orlistat