Metabolism in adipose tissue in response to citalopram and trimipramine treatment--an in situ microdialysis study.

The intake of antidepressants is often accompanied by weight gain. Antidepressants may influence lipid and carbohydrate metabolism that can result in metabolic changes and obesity. We investigated the effect of citalopram and trimipramine on interstitial glycerol, glucose and lactate concentration and blood flow in subcutaneous adipose tissue of obese subjects by means of the microdialysis technique. In addition, the effect of stimulation with norepinephrine on metabolic response was investigated. Each subject was compared to a control subject matched for BMI and age. Each group comprised 10 subjects. Circulating plasma triglyceride concentrations were higher in drug-treated groups. In subcutaneous adipose tissue, microdialysis experiments revealed a higher and prolonged glycerol release in the presence of norepinephrine, but not under basal conditions. In citalopram treated subjects, basal glucose and lactate concentrations were higher compared with controls or with the trimipramine treated group. Local administration of norepinephrine induced a decrease in glucose levels and an increase in lactate levels, but without significant differences between groups. Local adipose tissue blood flow decreased in control groups following norepinephrine application, but remained constant in the antidepressant groups. In conclusion, citalopram and trimipramine affected glucose and lipid metabolism in adipose tissue and resulted in enhanced release of glycerol and free fatty acids into the circulation.

Studies of phosphodiesterase effects on adipose tissue metabolism in obese subjects by the microdialysis technique.

The effect of non-selective (theophylline) inhibition of cyclic AMP breakdown on norepinephrine stimulated lipolysis rate was investigated in subcutaneous adipose tissue of obese subjects. In addition, changes in interstitial glucose and lactate concentration were assessed by means of the microdialysis technique. The interaction of endogenous released insulin and theophylline on adipocyte metabolism was determined. Theophylline and norepinephrine alone increased glycerol outflow significantly. When both agents were perfused in combination, interstitial glycerol concentration increased further. The enhanced glycerol level due to theophylline application was slightly decreased by insulin. In the presence of theophylline, extracellular glucose concentration increased, in contrast to the catecholamine. Norepinephrine decreased interstitial glucose level. When both drugs were added in combination, the level of interstitial glucose increased to about 1 mM, greater than with theophylline alone. With each intervention, lactate was synthesized. Local adipose tissue blood flow was increased by theophylline and theophylline plus norepinephrine. In conclusion, post-receptor mechanisms increased norepinephrine maximal stimulated lipolysis rate in subcutaneous adipose tissue. Glucose uptake was inhibited by the non-specific inhibitor of phosphodiesterase. The effect of insulin on inhibition of lipolysis was modest but sustained in the presence of high theophylline (10(-4) M) concentration. Phosphodiesterase activity may be relatively low in obese subjects in comparison with lean subjects. In lean subjects theophylline caused a transient reversal of the antilipolytic effect of insulin.

Effects of moderate consumption of white wine on weight loss in overweight and obese subjects.

BACKGROUND: Patients on dietary, weight-reducing treatment commonly are advised against alcohol consumption. In light of the widespread use of alcoholic beverages and the well-established benefits of light to moderate alcohol consumption in risk reduction, a revision of dietary treatment recommendations may be warranted. OBJECTIVE: To investigate whether daily consumption of moderate amounts of alcohol influences the effectiveness of an energy-restricted diet in overweight and obese subjects. DESIGN: A prospective randomized clinical trial was conducted, with a 3-months intervention period and two isocaloric dietary regimens containing 6.3 MJ (1500 kcal) each, one with 10% of energy from white wine and one with 10% of energy from grape juice. The trial was performed in obese subjects being recruited from the Obesity Outpatient Clinic at the University Hospital, Ulm, who all habitually consumed moderate amounts of alcohol. Out of 87 patients, 49 were eligible to participate and 40 completed the study (age 48.1+/-11.4 y, BMI 34.2+/-6.4 kg/m(2)). Efficacy parameters were body weight and biomarkers of good health. RESULTS: All subjects achieved significant body weight reduction. Weight loss in the grape juice group and white wine group was 3.75+/-0.46 and 4.73+/-0.53 kg, respectively. Percent body fat, waist circumference, blood pressure, blood glucose, insulin, triglycerides, and cholesterol were reduced. The antioxidant status was unchanged, as were liver enzyme activities and other safety parameters. There were no significant differences between the groups. CONCLUSIONS: An energy-restricted diet is effective in overweight and obese subjects used to drinking moderate amounts of alcohol. A diet with 10% of energy derived from white wine is as effective as an isocaloric diet with 10% of energy derived from grape juice.

Lipoprotein responses to weight loss and weight maintenance in high-risk obese subjects.

OBJECTIVE: To examine changes in plasma lipids and lipoproteins after 51 months of reduced energy intake and sustained weight loss. METHODS: One-hundred patients were randomized to one of two dietary interventions for 3 months (weight loss period). Groups A and B received an energy-restricted diet plan of 5.2-6.3 MJ/day but group B was further instructed to replace two of three meals with a nutrient-fortified liquid meal replacement (MR). Upon completion of the weight loss period, all patients were given the same instructions regarding energy intake and were advised to use one MR daily. Body weight and 7 day food diaries were measured monthly or bimonthly and blood lipids at baseline, 3, 9 and 51 months. RESULTS: Of the original 100 patients 75 had completed 4 y. Of those 75, 73 had complete lipid records. Baseline body weights of Groups A and B were 90.7+/-14.0 and 91.6+/-9.8 kg, respectively. The percentage change in total cholesterol (%DeltaTC) decreased in a linear fashion with increasing weight loss, when all data was combined, but did not approach statistical significance (P< or =0.26, r=0.02). Further regression analysis found a significant negative linear relationship (P< or =0.0001, r=0.69) between initial total cholesterol (TC) concentrations and %DeltaTC. Hence, data from 27 of the 73 completers who exhibited an elevated serum total cholesterol (> or =6.2 mmol/l) were isolated and analyzed further. Baseline TC was 6.75+/-0.64, 5.85+/-0.63 at 9 months (P<0.05) and 5.76+/-0.52 mmol/l at 51 months (P<0.05). Similar values for VLDL-cholesterol were 1.33+/-0.80, 0.74+/-0.24 and 0.66+/-0.21 mmol/l by 51 months (P<0.05). Weight decreased by 5.2+/-5.1, 7.6+/-4.9 and 6.7+/-4.6% at 3, 9 and 51 months, respectively. CONCLUSION: Continuous energy restriction associated with a clinically meaningful weight loss significantly improved the lipid profile of high-risk patients. Similar weight and diet changes occurring in patients with normal plasma cholesterol were either increased or without affect.

In vivo alpha(1)-adrenergic lipolytic activity in subcutaneous adipose tissue of obese subjects.

The role of alpha(1)-adrenoceptors in lipid mobilization and blood flow was investigated in situ using microdialysis of subcutaneous adipose tissue in severely obese subjects. The lipolysis rate was assessed by determination of interstitial glycerol concentration. The alpha(1)-adrenoceptor agonist norfenefrine caused an increase in glycerol level in adipose tissue that was similar to that observed with the physiologic alpha(1,2)-beta(1)-adrenoceptor agonist norepinephrine, whereas the alpha(1)-adrenoceptor antagonist urapidil showed no effect on basal lipolysis rate. However, the enhanced glycerol concentration due to norfenefrine and norepinephrine was suppressed in the presence of urapidil. The beta-adrenoceptor antagonist propranolol showed no effect on norfenefrine-stimulated glycerol outflow. Blood flow was assessed using the ethanol escape technique. Perfusion with norfenefrine decreased blood flow, whereas urapidil enhanced blood flow significantly. Despite the increase in blood flow, the basal interstitial glycerol concentration remained unchanged. Although norfenefrine at high concentrations could inhibit the urapidil-induced increase in blood flow, the norfenefrine-induced glycerol output was not affected. These results demonstrate that alpha(1)-adrenoceptors are involved in regulation of lipolysis rate and microcirculation of adipose tissue. However, the observed changes in local blood flow were not related to glycerol output.

Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects.

BACKGROUND: Acipimox is a hypolipidaemic agent reducing serum concentrations of triglycerides and non-esterified fatty acids. Acipimox may reduce triglyceride synthesis by decreasing non-esterified fatty acid availability from adipocytes, but this effect has yet to be demonstrated in vivo. Lipolysis after acipimox treatment was examined in subcutaneous adipose tissue of severely obese subjects with associated metabolic disorders. METHODS: The microdialysis technique was performed in abdominal subcutaneous adipose tissue of eight hyperinsulinaemic subjects. After oral treatment with acipimox, glycerol concentration was determined as an index of lipolysis rate. Blood flow was assessed by the ethanol escape technique. The rates of release of glycerol from human adipose tissue maximally stimulated by norepinephrine were also investigated in the presence of acipimox. Eight weight- and age-matched subjects served as a control group. RESULTS: Under acipimox treatment, basal glycerol release decreased in subcutaneous adipose tissue, whereas no effect was observed on blood flow. In stimulated adipose tissue acipimox showed no effect. CONCLUSION: In the present study basal glycerol outflow from adipose tissue was inhibited by acipimox. The anti-lipolytic action of the agent may diminish elevated plasma concentrations of free fatty acids in subjects with severe obesity.

Value of structured meals for weight management: risk factors and long-term weight maintenance.

OBJECTIVE: To examine changes in biomarkers of disease risk after 51 months of reduced energy intake and sustained weight loss. RESEARCH METHODS AND PROCEDURES: This study was conducted as a prospective, randomized, two-arm, parallel intervention for 12 weeks followed by a prospective, single-arm, 4-year trial in a university-based hospital clinic. One hundred patients were randomly assigned to one of two dietary interventions for 3 months. Group A was prescribed an energy-restricted diet of 1200 to 1500 kcal/d, and group B was prescribed an isocaloric diet, whereby two of three meals were replaced with nutrient-fortified liquid meal replacements. After 3 months, the patients were prescribed the same caloric reduction and used once-daily replacements for the succeeding 4 years. Body weight and blood pressure were checked monthly. Biomarkers of disease risk were measured after 3, 9, 15, 27, and 51 months. RESULTS: During the 3-month weight-loss period, body weight was reduced by 1.5 +/- 0.4% and 7.8 +/- 0.5% (mean +/- SEM) for groups A and B, respectively. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.3 +/- 0.8% and 8.4 +/- 0.8% for groups A and B, respectively. Both groups of patients showed significant improvement in glucose, insulin, triacylglycerol, and systolic blood pressure. Cholesterol concentrations were reduced in patients with high initial cholesterol levels and maintenance of a 7% weight loss. DISCUSSION: Providing a structured meal plan with liquid meal replacements is an effective treatment for obese subjects. Long-term maintenance of weight loss with meal replacements improves biomarkers of disease risk.

[Principles of dietary treatment of obesity]. / Grundlagen der Diättherapie der Adipositas.

One of the first steps in a clinical approach to any obese subject should be focused on the reduction and/or normalization of any potential or existing metabolic abnormality. Overeating and/or unbalanced food intake remains the major element in the origin and maintenance of obesity. The reduction of energy intake is the basis of successful weight loss. In obese subjects there are huge amounts of energy stored, mainly in the adipose tissue, which are mobilized according to the size and duration of an energy deficit. Considerable studies have been devoted to finding the optimal dietary approach that would promote rapid weight loss while maximizing the depletion of adipose tissue and conserving body protein. During fasting adipose tissue lipolysis rate increases and liberated unesterified fatty acids are oxidized in muscle and liver. The liver produces ketones which are oxidized in muscle and brain. The energy need of the brain is not sufficiently covered by ketone oxidation, therefore additional glucose must be provided. The liver produces glucose by gluconeogenesis using amino acids from muscle protein. Because of limited protein sources, protein must be given during energy restricted diet. Besides protein also vitamins, minerals, trace elements, fiber, and linoleic acid must be substituted during fasting and during treatment with very low calorie diets. Meal replacements are helpful to fulfil all the requirements. There is consensus that the first step in dietary treatment is an energy restricted diet with a calorie deficit of at least 600 Kcal/day, but more than 800 Kcal/day must be provided, with all essential nutrients. Observing the regulations, weight reduction with appropriate diet plans improves metabolic disturbances.

Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.

OBJECTIVE: To investigate the contribution of meal and snack replacements for long-term weight maintenance and risk factor reduction in obese patients. RESEARCH METHODS AND PROCEDURES: Prospective, randomized, two-arm, parallel intervention for 12 weeks followed by a prospective single-arm 4-year trial in a University Hospital clinic. One hundred patients, >18 years old and with a body mass index > 25 and < or = 40 kg/m2, were prescribed a 1,200 to 1,500 kcal/d control diet (Group A) or an isoenergetic diet, including two meal and snack replacements (vitamin- and mineral-fortified shakes, soups, and bars) and one meal high in fruits and vegetables (Group B). Following a 3 months of weight loss, all patients were prescribed the same energy-restricted diet (1,200 to 1,500 kcal) with one meal and one snack replacement for an additional 4 years. RESULTS: All 100 patients were evaluated at 12 weeks. Mean percentage weight loss was 1.5 +/- 0.4% and 7.8 +/- 0.5% (mean +/- SEM) for Groups A and B, respectively. At 12 weeks systolic blood pressure, plasma triacylglycerol, glucose, and insulin concentrations were significantly reduced in Group B, whereas no changes occurred in Group A. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.2 +/- 0.8% for Group A and 8.4 +/- 0.8% (mean +/- SEM) for Group B. Both groups showed significant improvement in blood glucose and insulin (p < 0.001), but only Group B showed significant improvement in triacylglycerol and systolic blood pressure compared to baseline values (p < 0.001). DISCUSSION: Providing a structured meal plan via vitamin- and mineral-fortified liquid meal replacements is a safe and effective dietary strategy for obese patients. Long-term maintenance of weight loss with meal replacements can improve certain biomarkers of disease risk.

Reduced epinephrine-stimulated lipolytic activity in male golden-mantled ground squirrel during hibernation: an in situ microdialysis study.

We studied lipolytic activities in vivo in golden mantle ground squirrels during pre-hibernation and hibernation using microdialysis technique. Microdialysis probes were inserted into the abdominal subcutaneous adipose tissues. Baseline lipolysis were assessed by measuring glycerol concentration. Epinephrine-stimulated lipolysis was also examined. Eight squirrels (four male, four female) were studied in each of the two stages. Basal glycerol concentrations were lower in the hibernating state than in the pre-hibernation state in male squirrels (P < 0.05). Epinephrine application induced glycerol release in male and female squirrels (P < 0.001) in both stages. Male squirrels demonstrated a reduced epinephrine-stimulated glycerol release in the hibernating state, which was not observed in female squirrels.

Sympathetic modulation of lipolysis in subcutaneous adipose tissue: effects of gender and energy restriction.

To investigate the differences in the regulation of lipolysis between male and female obese subjects in vivo, we used an in situ microdialysis technique before and after 3 weeks of energy restriction. Using this method, we examined glycerol, glucose, and lactate responses after 5 minutes of epinephrine stimulation in the adipose tissues. Glycerol releases after the perfusion of phentolamine, orciprenaline, and propranolol were also studied. Sixteen subjects were studied (8 men, 8 women, 35 to 45 years of age, body mass index 38 to 50 kg/m2). In women, epinephrine provoked a greater glycerol release than in men in both abdominal and femoral regions (P < .05). In men and women there was a significant decrease in the concentration of glucose and a significant increase in lactate concentration after epinephrine stimulation (P < .001). After 3 weeks of energy restriction, glycerol release after epinephrine stimulation was greater in both sexes than that observed before energy restriction (P < .05). Both phentolamine and orciprenaline stimulated the release of glycerol (P < .01); phentolamine had a higher effect in women, while propranolol had no effect on glycerol release in both sexes. In summary, we have demonstrated that epinephrine provoked a greater lipolytic response in obese women in both abdominal and femoral adipose tissues. The lipolytic response was further enhanced after 3 weeks of energy restriction in each gender. The decrease in glucose concentration suggests that glucose may be reutilized for synthesis into new triacylglycerol. Knowledge about the sensitivity to lipolytic agents in subcutaneous adipose tissue may provide potential new approaches for modulating the lipolytic responses of subcutaneous adipose tissue differently in men and women.

Metabolic and weight-loss effects of a long-term dietary intervention in obese patients.

BACKGROUND: Obesity is a chronic disease that has become one of the most serious health problems in Western society. OBJECTIVE: We assessed the long-term effects of an energy-restricted diet combined with 1 or 2 daily meal replacements on body weight and biomarkers of disease risk in 100 obese patients. DESIGN: Phase 1 consisted of a 3-mo, prospective, randomized, parallel intervention study of 2 dietary interventions to reduce weight. The energy-restricted diet (5.2-6.3 MJ/d) consisted of conventional foods (group A) or an isoenergetic diet with 2 meals and 2 snacks replaced daily by energy-controlled, vitamin-and-mineral-supplemented prepared foods (group B). Phase 2 consisted of a 24-mo, case-control, weight-maintenance study with an energy-restricted diet and 1 meal and 1 snack replaced daily for all patients. RESULTS: Total weight loss (as a percentage of initial body weight) was 5.9+/-5.0% in group A and 11.3+/-6.8% in group B (P < 0.0001). During phase 1, mean weight loss in group B (n = 50) was 7.1+/-3.5 kg, with significant reductions in plasma triacylglycerol, glucose, and insulin concentrations (P < 0.0001). Group A patients (n = 50) lost an average of 1.3+/-2.2 kg with no significant improvements in these biomarkers. During phase 2, both groups lost on average an additional 0.07% of their initial body weight every month (P < 0.01). During the 27-mo study, both groups experienced significant reductions in systolic blood pressure and plasma concentrations of triacylglycerol, glucose, and insulin (P < 0.01). CONCLUSION: These findings support the hypothesis that defined meal replacements can be used for successful, long-term weight control and improvements in certain biomarkers of disease risk.

Metformin inhibits catecholamine-stimulated lipolysis in obese, hyperinsulinemic, hypertensive subjects in subcutaneous adipose tissue: an in situ microdialysis study.

AIMS: Metformin has been reported to decrease the plasma concentrations of non-esterified fatty acids in Type 2 diabetic subjects. This study investigated the effects of metformin on basal and catecholamine-stimulated lipolysis in abdominal subcutaneous adipose tissue of obese, hyperinsulinaemic, hypertensive subjects. METHODS: Fourteen subjects with severe obesity (12 female, twomale, age 35.4 +/- 4 years, body mass index 48.2 +/- 2 kg/m2, body fat mass 63.3 +/- 5 kg) were recruited. Glycerol and lactate concentrations were determined in the presence of metformin and after administration of catecholamines using microdialysis. Simultaneously, blood flow was assessed with the ethanol escape method. RESULTS: Glycerol release was lowered by metformin during the 3-h experiment (P<0.01). The lipolytic activity of catecholamines was suppressed when adipose tissue was pre-treated with metformin (P<0.001). Lactate concentration increased after application of metformin (P<0.01) and catecholamines (P<0.001). Blood flow was decreased in the presence of adrenaline (P < 0.01), but this effect was abolished by metformin. CONCLUSIONS: The present data demonstrate the effects of metformin on lipolysis in subcutaneous adipose tissue in vivo. In the large body fat mass of obese subjects, a reduction of lipolysis in adipose tissue may contribute to a decrease of VLDL synthesis in the liver resulting in a lowered plasma triglyceride concentration.

Blood pressure and plasma norepinephrine responses to dexfenfluramine in obese postmenopausal women.

Dexfenfluramine has been shown to reduce body weight and lower blood pressure in obese individuals. However. it is not clear whether the blood pressure-lowering effect is due to dexfenfluramine or to the loss of weight. This project was designed to study the effect of a 5-d treatment of dexfenfluramine on blood pressure changes in obese postmenopausal women. Twenty women aged 51-60 y matched for body mass index [BMI (in kg/m2) of 34.5-50.1] were assigned to either the dexfenfluramine group (15 mg orally twice a day for 5 d) or the control group. All subjects were instructed about an isoenergetic diet. Twenty-four-hour ambulatory blood pressure, plasma catecholamines, glucose, insulin, and lipids were measured at the beginning and repeated at the conclusion of the study. On day 5 the mean systolic (SBP) and mean diastolic blood pressures (DBP) in the dexfenfluramine group were lower than those of the control group (SBP: 114+/-7 mm Hg in the dexfenfluramine group compared with 124+/-12 mm Hg in the control group, P < 0.05; DBP: 70+/-9 mm Hg in the dexfenfluramine group compared with 76+/-10 mm Hg in the control group, P < 0.05). The mean plasma norepinephrine concentration was lower in the dexfenfluramine group than in the control group (1.60+/-0.5 compared with 2.41+/-0.5 nmol/L, respectively, P < 0.05). No differences were noted in epinephrine, glucose, insulin. and lipid concentrations between the two groups. We showed that a 5-d treatment of dexfenfluramine decreases blood pressure and reduces heart rate in obese postmenopausal women. Our data suggest that these effects are results of the direct action of dexfenfluramine.

Proximal gastric motility functions are normal in severe obesity.

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.

The effects of dexfenfluramine on weight loss and cardiovascular risk factors in female patients with upper and lower body obesity.

BACKGROUND: Obesity has been identified as a risk factor for atherosclerosis, and fat distribution has proved to be a critical variable. Weight loss improves health, but failure rates in dietary treatment are high. The effects of dexfenfluramine, which is useful in many patients, were studied on cardiovascular risk factors in obese female patients with upper and lower body obesity. METHODS: In a placebo-controlled, double-blind trial, which was part of a multicentre study, 52 obese female patients (body mass index 35.1 +/- 7.8 kg/m2, age 43.3 +/- 6.4 years) were given either 15 mg dexfenfluramine twice daily, or placebo in addition to a calorie-restricted diet (1500 kcal/day) for 12 months. Forty-two patients (20 with upper body obesity, 12 dexfenfluramine and 10 placebo; 22 with lower body obesity, 16 dexfenfluramine and six placebo) completed the 14-month study. RESULTS: Patients with upper body obesity lost 14.2 +/- 2.20 kg with dexfenfluramine, and 4.92 +/- 2.99 kg with placebo (P < or = 0.05). In contrast, patients with lower body obesity lost 11.1 +/- 2.89 kg with dexfenfluramine and 2.6 +/- 2.32 kg with placebo (P < 0.05). With dexfenfluramine, patients with upper body obesity lost more weight than patients with lower body obesity (P < 0.05). After 1 year of dexfenfluramine treatment, reduction of systolic blood pressure in patients with upper body obesity (157 +/- 10 versus 133 +/- 8 mmHg, P < 0.05) was significantly (P < 0.05) greater than in patients with lower body obesity (136 +/- 14 versus 127 +/- 12 mmHg). During dexfenfluramine treatment cardiovascular risk factors improved. In upper body obesity blood glucose (5.18 +/- 0.28 versus 4.40 +/- 0.34 mmol/l, P < 0.05), serum insulin (23.4 +/- 8.9 versus 13.2 +/- 4.2 microU/ml, P < 0.05) and triglycerides (1.96 +/- 0.45 versus 1.23 +/- 0.54 mmol/l, P < 0.05) decreased, and high-density lipoprotein cholesterol increased (1.0 +/- 0.14 versus 1.21 +/- 0.14 mmol/l P < 0.05). In lower-body obesity, cardiovascular risk factors were in the normal range and did not change significantly during the study. CONCLUSIONS: Dexfenfluramine lowers body weight in obese patients with upper and lower body obesity and reduces the cardiovascular risk factors clustering in upper body obesity.

The effect of withdrawal and re-introduction of dexfenfluramine in the treatment of obesity.

In this study 25 patients, who had completed the INDEX trial (Guy-Grand et al. Lancet 1989; 2: 1142-1145) were reexamined 2 months after withdrawal of the study medication. The patients then in an open trial received dexfenfluramine (dF) for 6 months. The observed weight gain after withdrawal of study medication was higher in patients treated beforehand with dF (2.6 +/- 1.2 kg) than in patients who had received placebo (0.8 +/- 1.0 kg). In the open dF trial rate of weight loss was lower than it had initially been in the patients receiving dF from the outset of the INDEX trial (13.1 +/- 4.6 kg within 6 months). In the previous dF treated patients weight loss after re-introduction of dF was 3.7 +/- 2.7 kg. The previous placebo-treated patients, now receiving dF for the first time, lost 4.8 +/- 1.1 kg. Thus, after withdrawal of dF, patients experience weight gain, but after re-introduction of dF, renewed weight loss is achieved. However, the rate of weight loss declines with time.

Fibrinogen in obesity before and after weight reduction.

Several studies have shown that obesity is associated with atherosclerosis. The reason may be that there is often a gathering together of risk factors for cardiovascular disease in obesity. Recently plasma fibrinogen level has been identified as an important cardiovascular risk factor. The aim of the study was to investigate fibrinogen levels in obesity before and after weight reduction. Obese but otherwise healthy patients with overweight problems were studied. 448 female patients (39.1 +/- 13.2 years, body mass index 38.7 kg/m2) and 136 male patients (39.4 +/- 12.8 years, body mass index 40.7 kg/m2) were examined after overnight fasting. Sixty patients (44 female, 16 male) were studied after 9.5 +/- 6.2 month of dieting (1200 kcal/day: 20% protein, 30% fat and 50% carbohydrates). The weight loss was 16.7 +/- 11.0 kg in the female and 16.2 +/- 6.7 kg in the male patients, and blood pressure, triglycerides, blood glucose and uric acid had declined. The fibrinogen level correlated with the body mass index, the waist circumference, the hip circumference and the waist to hip ratio. The fibrinogen level also correlated with insulin. A partial correlation of fibrinogen and insulin continued to exist after removing the linear effects of the other variables measured. After weight reduction, the level of fibrinogen was lower. In patients with extreme overweight and high fibrinogen levels, who reduced their BMI by 7.4 +/- 1.24 kg/m2, the weight loss correlated with the decrease in fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine and metabolic effects of dexfenfluramine in patients with android obesity.

The effects of dexfenfluramine on 24-hour profiles of ACTH, GH, norepinephrine, insulin and FFA were studied in a group of obese male patients. A controlled comparison trial under metabolic ward conditions was conducted. Dexfenfluramine (15 mg twice daily) was given for 8 days, while patients adhered to a weight maintaining diet. 9 obese patients were treated with dexfenfluramine. 9 obese patients who were randomized on the basis one after another served as a control group. After a 3 day run-in period at 8 am, 10 am, and 4 pm, 8 pm and 12 pm, and 8 am of the following day ACTH, GH, norepinephrine, insulin and FFA were measured before and during the 8th day of dexfenfluramine treatment. During the study body weight slightly decreased in both groups. In the DF group systolic and diastolic blood pressure declined during treatment. The norepinephrine levels were depressed during DF treatment over the entire day. The 24-hour profile of ACTH levels changed in the treatment group to a more distinct circadian rhythm with slightly higher levels in the morning and lower levels at night. The 24-hour profile of GH changed in the drug treated group with a diminished peak of GH secretion at night. Serum concentrations of insulin and FFA were decreased during DF treatment. The hormonal changes during dexfenfluramine treatment suggest that the drug affects endocrine mechanisms that may be involved in regulation of energy balance. Treatment with dexfenfluramine results in decrease of FFA. The mechanisms by which dexfenfluramine operates and displays its various effects on hormones and lipolysis have not been studied.