Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Overweight and Obesity Based on Four Reference Systems in 18,382 Paediatric Patients with Type 1 Diabetes from Germany and Austria.

AIM: To evaluate the prevalence of overweight and obesity in paediatric type 1 diabetes (T1D) subjects, based on four commonly used reference populations. METHODS: Using WHO, IOTF, AGA (German pediatric obesity), and KiGGS (German Health Interview and Examination Survey for Children and Adolescents) reference populations, prevalence of overweight (≥90th percentile) and obesity (≥97th percentile) and time trend between 2000 (n = 9,461) and 2013 (n = 18,382) were determined in 2-18-year-old T1D patients documented in the German/Austrian DPV database. RESULTS: In 2000, the overweight prevalence was the highest according to IOTF (22.3%), followed by WHO (20.8%), AGA (15.5%), and KiGGS (9.4%). The respective rates in 2013 were IOTF (24.8%), WHO (22.9%), AGA (18.2%), and KiGGS (11.7%). Obesity prevalence in 2000 was the highest according to WHO (7.9%), followed by AGA (4.5%), IOTF (3.1%), and KiGGS (1.8%). In 2013, the respective rates were WHO (9.6%), AGA (6.2%), IOTF (4.5%), and KiGGS (2.6%). Overall, the prevalence of overweight and obesity increased from 2000 to 2006 (p < 0.001) but showed stabilization thereafter in girls and overweight in boys. CONCLUSION: Overweight and obesity prevalence in T1D subjects differs significantly if it is assessed by four separate reference populations. More detailed assessment of each child is required to determine obesity-related risks.

Influence of plasma cortisol and other laboratory parameters on nonalcoholic Fatty liver disease.

The objective of the present study was to analyse the association between the plasma cortisol concentration and nonalcoholic fatty liver disease (NAFLD). A total of 1 326 subjects (age 18-65 years) were examined in the context of an epidemiological study of a population-based random sample. Medical history and anthropometric data of 662 women and 664 men were documented. In addition, laboratory examinations were performed and the fat concentration of the liver was estimated by ultrasound examination. Mean cortisol concentration in plasma was 260.4±156.8 nmol/l for women and 295.8±161.2 nmol/l for men. NAFLD was identified in 17.7% in women and 35.1% in men. Plasma cortisol concentration showed no association with the existence of NAFLD. NAFLD correlated positive with age, body-mass index (BMI), waist-to-hip-ratio (WHR), alanine aminotransferase (ALT), and triglycerides. The present study failed to establish any association of plasma cortisol concentrations and NAFLD.

Associations of fatty liver disease and other factors affecting serum SHBG concentrations: a population based study on 1657 subjects.

Sex hormone binding globulin (SHBG) is a glycoprotein expressed predominantly in the hepatocytes. It regulates the transport of sex steroid hormones in the blood stream to their target tissues. The expression of the SHBG gene is subject to multifactorial regulation including hormonal, metabolic, and nutritional aspects. Against this background, we investigated the effect of fatty liver and metabolic syndrome, together with other parameters, on serum SHBG concentrations in a population-based cohort in Germany. This cross-sectional study included 870 women and 787 men (average age 42.3±12.8 years), who underwent ultrasound screening for fatty liver in addition to providing a complete medical history and undergoing physical and laboratory examination. Fatty liver was diagnosed on ultrasound criteria in 159 women (18.3%) and 287 men (36.5%). Fatty liver was shown to exert a significant influence on serum SHBG concentrations in men and in premenopausal women. Men with grade 1 fatty liver had a 1.96-fold increased risk (95%-confidence interval=1.28-3.02; p=0.0022) and postmenopausal women with grade 1 fatty liver a 2.4-fold risk (95%-confidence interval=1.11-5.27; p=0.0267) for low SHBG concentrations. Among metabolic parameters, HDL-C represented as affecting factor in men (p=0.0058) and premenopausal women (p=0.0002), while cholesterol only showed an association in premenopausal women (p=0.0439) and triglyceride in postmenopausal women (p=0.0436). No association of concentrations of SHBG and metabolic syndrome was observed. Age, BMI and waist-to-hip ratio also influence the SHBG concentration. Based on these findings, we conclude that fat accumulation in the liver influences SHBG concentrations in men and premenopausal women.

[Hypertension, dyslipoproteinemia and BMI-category characterise the cardiovascular risk in overweight or obese children and adolescents: data of the BZgA-observational study (EvAKu-J-project) and the KiGGS-study]. / Hypertonie, Dyslipoproteinämie und BMI-Kategorie charakterisieren das kardiovaskuläre Risiko bei übergewichtigen oder adipösen Kindern und Jugendlichen: Daten der BZgA-Beobachtungsstudie (EvAKuJ-Projekt) und der KiGGS-Studie.

BACKGROUND: The considerable increase of obesity in children and adolescents poses a major challenge to the health care system. METHODS: In an observation study of the Bundeszentrale für gesundheitliche Aufklärung (BZgA) somatic data of 1916 overweight and obese children and adolescents aged 8-17 years were compared to data of 7 451 normal weight children and adolescents (KiGGS). Age, sex, body weight, height, BMI-SDS, blood pressure, and lipids were analyzed. Body weight was assessed using the BMI categories of the Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter (AGA) guidelines. Blood pressure measurements were given as above 95 (th) percentile and categorized according to the classification of the European Society of Hypertension (ESH). In addition blood pressure in BZgA-patients were estimated as above 95 (th) percentile by age, sex and height in German normal weight children and adolescents. Lipid values were evaluated according to American Heart Association specifications. RESULTS: Out of the participants of BZgA-study 14% were overweight, 48% obese, and 38% extremely obese. Blood pressure values were above the 95 (th) percentile (ESH) in 35%. The blood pressure in normal weight participants of the KiGGS-study were elevated in 5%. Total cholesterol of BZgA-patients was elevated in 13%, LDL-cholesterol was elevated in 13%, HDL-cholesterol was low in 7%, and triglycerides in the fasting state were elevated in 12%. CONCLUSIONS: The rising prevalence of cardiovascular risk factors in children and adolescents with increasing BMI category requires effective strategies for prevention and treatment of obesity.

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.

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.

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.