Very-low-energy Diet Research Articles

Effect of Orlistat on Eating Behavior Among Participants in a 3‐year Weight Maintenance Trial

To examine the effect of orlistat on dietary restraint, disinhibition, hunger, and binge eating and to understand the relation between changes in eating behavior and weight maintenance. Subjects were 306 women and men (age: 19-45 years; BMI: 37.5 +/- 4.1 kg/m(2)) included in the Scandinavian Multicenter study of Obese subjects with the Metabolic Syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week very low energy diet (VLED). Outcomes were changes in weight and in the Three Factor Eating Questionnaire (TFEQ) and Binge Eating Scale (BES) between screening and 17 and 33 months after randomization. As reported previously, weight gain following VLED was lower in subjects treated with orlistat than with placebo. Compared to screening results, dietary restraint was increased and disinhibition, hunger, and binge eating were decreased in both groups. These changes were similar in both groups with the exception of the hunger score at month 33 that was reduced more in the placebo than in the orlistat group (difference between groups -1.1 (95% CI (-2.0, -0.2)) P = 0.014). In multivariate analyses, scores for restraint, disinhibition and binge eating were associated with weight loss after adjustment for BMI, gender, age, and treatment (all P < or = 0.002, model R (2) = 0.12-0.17). Orlistat did not affect eating behavior differently in any substantial way than the placebo did in this long-term weight maintenance trial. The results indicate that increased restraint and decreased disinhibition and binge eating are important for sustained weight maintenance in obese subjects with the metabolic syndrome.

A retrospective comparison of two very low energy diets on weight loss and health status in obese women completing a 26-week program

To retrospectively compare the effects of two very low energy diets (VLED) on weight, girths, and health status by auditing clinic database. Obese women (n = 150) who consumed either 420 kcal/day (n = 75) or 800 kcal/day (n = 75) were retrospectively matched for age, height and entry weight. The 26-week program comprised 12 weeks of 420 or 800 kcal/day energy intake then 12 weeks of reintroduction of normal food, with behavioural management. Pre-post measures of weight, BMI, girths, blood pressure (BP) and blood glucose, cholesterol and triglycerides were made. Within groups, all variables significantly improved at 26 weeks, except fasting glucose (420 group only). In the 420 and 800 groups, mean weight loss was 18.7 and 19.0 kg, BMI reduced by 7.7 and 7.0 kg/m(2), waist girth by 15.6 and 16.2 cm and hip girth by 16.5 and 14.1 cm (all p < 0.001). With weight loss expressed as % of entry weight, 58.7% of the 420 and 42.6% of the 800 groups lost >20% weight (p = 0.05). The only post-between group differences were in decreases in systolic BP (14 mmHg in 420 vs. 7 mmHg in 800; p < 0.05) and fasting glucose (0.1 mmol/L in 420 vs. 0.4 mmo1/L in 800; p < 0.05). Both levels of VLED with behavioural management produced similar improvements in weight and health status in obese women after 26 weeks. A VLED of 800 kcal/day (instead of 420) might be recommended for calorie control programs, to minimise health risks, while producing similar improvements in weight and health.

The effect of total starvation and very low energy diet in lean men on kinetics of whole body protein and five hepatic secretory proteins

It is unclear whether the rate of weight loss, independent of magnitude, affects whole body protein metabolism and the synthesis and plasma concentrations of specific hepatic secretory proteins. We examined 1) whether lean men losing weight rapidly (starvation) show greater changes in whole body protein kinetics, synthesis, and circulating concentrations of selected hepatic secretory proteins than those losing the same amount of weight more slowly [very low energy diet (VLED)]; and 2) whether plasma concentrations and synthetic rates of these proteins are related. Whole body protein kinetics were measured using [1-(13)C]leucine in 11 lean men (6 starvation, 5 VLED). Fractional and absolute synthetic rates of HDL-apolipoprotein A1 (apoA1), retinol binding protein, transthyretin, alpha(1)-antitrypsin (alpha(1)-AT), and transferrin were measured using a prime-constant intravenous infusion of [(13)C(2)]glycine. Compared with VLED group, the starvation group showed greater increases (at a 5% weight loss) in whole body protein oxidation (P < 0.05); fractional synthetic rates of HDL-apoA1 (25.3 vs. -1.52%; P = 0.003) and retinol binding protein (30.6 vs. 7.1%; P = 0.007); absolute synthetic rates of HDL-apoA1 (7.1 vs. -3.8 mg.kg(-1).day(-1); P = 0.003) and alpha(1)-AT (17.8 vs. 3.6 mg.kg(-1).day(-1); P = 0.02); and plasma concentration of alpha(1)-AT (P = 0.025). Relationships between synthetic rates and plasma concentrations varied between the secreted proteins. It is concluded that synthetic rates of hepatic secreted proteins in lean men are more closely related to the rate than the magnitude of weight loss. Changes in concentration of these secreted proteins can occur independently of changes in synthetic rates, and vice versa.

Impact of Different Levels of Weight Loss on Blood Pressure in Overweight And Obese Women

This study sought to determine the impact of different levels of weight loss on blood pressure in overweight/obese women. One hundred fifty-nine overweight/obese women (age 48.7 +/- 9.7, weight 101.3 +/- 18.7 kg, BMI 37.3 +/- 6.6 kg/m(2)) completed a six-month clinical weight loss program that included weekly nutrition, behavior, and exercise instruction. Participants consumed a very-low-energy diet (VLED) for 12 weeks. VLED was followed by four weeks of gradual reintroduction to solid foods. At week 16, participants received a diet to maintain weight or slightly reduce weight (<0.5 lb/week) which they followed for the duration of the study. All lab and blood pressure assessments were performed at baseline and six months. Three groups were formed according to the proportion of weight loss after six months; Group 1 had < 10% (n = 19), Group 2 had 10%-20% (n = 64), and Group 3 had >20% (n = 76) weight loss. Differences in systolic blood pressure (mm Hg) were found in dose response fashion for weight loss at six months with 125 +/- 17 (<10%), 119 +/- 13 (10%-20%), and 117 +/- 15 (>20%; p = 0.005). Differences in diastolic blood pressure (mm Hg) were also found in dose response fashion with 81 +/- 9 (<10%), 77 +/- 9 (10%-20%), and 75 +/- 9 (20%; p = 0.003). These data indicate that increasing weight loss beyond 10% of initial body weight may provide added improvements in blood pressure compared to less than 10% weight loss in overweight or obese women.

Effect of Orlistat on Weight Regain and Cardiovascular Risk Factors Following a Very-Low-Energy Diet in Abdominally Obese Patients

To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet (VLED) in obese patients with metabolic risk factors such as dyslipidemia, impaired fasting glucose, and diet-treated type 2 diabetes. Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day) in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost > or = 5% of their body weight (309 of 383 patients) were then randomized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d. or matching placebo capsules. Primary end points were the maintenance of > or = 5% weight loss after 3 years. Additionally, differences in the development of type 2 diabetes between orlistat and placebo were analyzed. The VLED induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized patients. The mean weight gain after 3 years was lower with orlistat than with placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037). Waist circumference was significantly more reduced in the orlistat group (P < 0.05), but no other differences in the risk factors were observed between the two groups. The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out of 156 subjects) (P = 0.041). The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects. The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes.

Preoperative weight loss with a very-low-energy diet: quantitation of changes in liver and abdominal fat by serial imaging1–3

A very-low-energy diet (VLED) can result in substantial, rapid weight loss and is increasingly prescribed before obesity surgery to minimize risk and difficulty by reducing liver size and abdominal adiposity. Despite its growing popularity, a VLED in this setting has received little attention. The aim of this study was to investigate the efficacy and acceptability of a preoperative VLED. In a prospective observational study, 32 subjects (n = 19 men and 13 women) with a mean (+/-SD) age of 47.5 +/- 8.3 y and a body mass index (in kg/m(2)) of 47.3 +/- 5.3 consumed a VLED for 12 wk. Primary outcomes included changes in liver volume (LV) and in visceral and subcutaneous adipose tissue (VAT/SAT). Changes in body weight, anthropometric measures, and biochemical variables were also recorded, and compliance with, acceptability of, and side effects of treatment were assessed. Changes in LV and VAT/SAT area were measured by computed tomography and magnetic resonance imaging at baseline and weeks 2, 4, 8, and 12. Mean (+/-SD) LV, VAT/SAT, and body weight decreased significantly (P < 0.001 for all). The degree of LV reduction was directly related to the reduction in relative body weight (r = 0.54, P = 0.001) and initial LV (r = 0.43, P = 0.015). Eighty percent of the reduction in LV occurred between weeks 0 and 2 (P < 0.001). Reductions in body weight and VAT were uniform over the 12-wk period. Attrition was 14%. Acceptability was adequate but waned over time, and mild transitory side effects occurred. Given the observed early reduction in LV and the progressive reduction in VAT, we suggest that the minimum duration for a preoperative VLED be 2 wk. Ideally, the duration should be 6 wk to achieve maximal LV reduction and significant reductions in VAT and body weight without compromising compliance and acceptability.

Nutrient-stimulated glucagon-like peptide 1 release after body-weight loss and weight maintenance in human subjects

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released in response to nutrient ingestion. Postprandial GLP-1 release has been reported to be attenuated in obese subjects, but reports on the effect of weight loss on GLP-1 are conflicting. The aim of the present study was to clarify the effect of a weight-loss period and a consecutive weight-maintenance period on nutrient-stimulated GLP-1 release in obese subjects. Nutrient-stimulated (standard breakfast; 1.9 MJ) GLP-1 release was investigated in thirty-two obese subjects on three occasions: before weight loss (T1) (BMI 30.0 (sd 2.5) kg/m(2)); after a 6-week very-low-energy diet (VLED) (T2) (BMI 27.6 (sd 2.3) kg/m(2)); after a 3-month weight-maintenance period (T3) (BMI 27.9 (sd 2.3) kg/m(2)). At each occasion, following a fasting blood sample the test meal was fed and blood was drawn every 30 min for 2 h relative to ingestion in order to determine plasma GLP-1, insulin, glucose and NEFA concentrations. Subjects lost 7 (sd 3.4) kg during the VLED (P<0.0001) and regained 1 (sd 3.2) kg during the weight-maintenance period (NS). The area under the curve for nutrient-stimulated plasma GLP-1 (pmol/l x h) was significantly decreased (P=0.01) at T2 (6.8 (sd 1)) compared with T1 (12.8 (sd 2.9)) and T3 (11.1 (sd 1.5)). Since we found a rebound of concentrations after a weight-maintenance period, decrease after weight loss seems to be transient and possibly due to a negative energy balance.

A Comparison of Meal Replacements and Medication in Weight Maintenance after Weight Loss

Objective: To compare the use of meal replacements or medication during weight maintenance subsequent to weight loss using a very low-energy diet (VLED) in overweight or obese adults.Design: Participants followed a liquid VLED of 2177 kJ for 12 weeks followed by 4 weeks of re-orientation to solid foods. Participants were randomized at week 16 to receive either meal replacements or Orlistat both combined with a structured meal plan containing an energy value calculated to maintain weight loss.Subjects: Sixty-four women (age = 49.9 ± 10 y, weight = 101.6 ± 17.1 kg, height = 164.9 ± 6.0 cm, BMI = 36.7 ± 5.4 kg/m2) and 28 men (age = 53.7 ± 9.6 y, weight = 121.8 ± 16.0 kg, height = 178.7 ± 5.6 cm, BMI = 37.8 ± 4.9 kg/m2) completed a 1 year weight management program. Behavioral weight management clinics included topics on lifestyle, physical activity (PA), and nutrition. Participants met for 90 min weekly for 26 weeks, and then biweekly for the remaining 26 weeks.Outcomes: Minutes of PA, fruits and vegetables (FV), and pedometer steps were recorded on a daily basis and reported at each group meeting. Body weight was obtained at each group meeting.Results: During VLED, the MR group decreased body weight by 22.8 ± 6.1 kg and the Orlistat group decreased body weight by 22.3 ± 6.1 kg. During weight maintenance, there was no significant group by time interaction for body weight, PA, FV consumption, or pedometer steps. At week 16, the meal replacement group had a body weight of 85.4 ± 14.3 kg that increased to 88.1 ± 16.5 kg at 52 weeks (p < 0.05). At week 16, the Orlistat group had a body weight of 85.7 ± 17.9 kg that increased to 88.5 ± 20.3 kg at 52 weeks (p < 0.05).Conclusions: Subsequent to weight loss from a VLED, meal replacements and Orlistat treatments were both effective in maintaining weight significantly below baseline levels over a 52 week period of time. Meal replacements may be a viable alternative strategy to medications for weight maintenance.

Health-related quality of life in obese outpatients losing weight with very-low-energy diet and behaviour modification--a 2-y follow-up study.

To study health-related quality of life (HRQL) in a clinically selected sample of obese outpatients. A single-strand before and after study with 2-y follow-up after treatment comprising 10 weeks on very-low-energy diet (VLED) and 4 months of behaviour modification in groups. A total of 126 (mean (s.d.) age 48.2 (11.1) y and body mass index 42.8 (6.2) kg/m(2) obese patients (63% women) referred for treatment in an obesity clinic. Weight and HRQL using questionnaires (RAND 36-Item Health Survey 1.0 and Obesity-related Psychosocial problems scale (OP-scale)). A total of 100 patients (61% women) completed the treatment and 67 (71% women) completed the 2-y follow-up. The mean (s.d.) weight loss was 12.5 (5.6)% at the end of group therapy, 6.0 (7.1)% at 1 y, and 2.6 (7.5)% at 2 y. At baseline, the mean (s.d.) score for the OP-scale was 61.9 (24.6). The mean scores on every RAND-36 scale were markedly lower than in the Finns without chronic conditions. All the scales in HRQL improved markedly during the treatment. During the follow-up, all the scales started to return towards baseline levels, and at 2 y only obesity-related psychosocial problems and physical functioning were still improved relative to baseline. In categories of weight change at 2 y (>or=10% weight loss, 0-9.9% weight loss, weight gain), obesity-related psychosocial functioning, physical functioning, and general health showed dose-response improvement with increasing weight loss. A >or=10% weight loss at 2 y after treatment was associated with clear improvement in obesity-related psychosocial problems, physical functioning, physical role functioning, bodily pain, general health, mental health, and vitality. A 0-9.9% weight loss was associated with improvement in obesity-related psychosocial problems and physical functioning. Weight gain was associated with improvement in obesity-related psychosocial problems and social functioning. The study population was too small to examine possible gender differences. Treatment with VLED and behaviour modification produces marked short-term weight loss and clear improvement in all aspects of HRQL. At 2 y after treatment, the average maintained weight loss is modest. However, 1/3 of patients maintained a >or=5% weight loss. Improvement in obesity-related psychosocial problems and physical functioning is associated even with less than 10% of maintained weight loss. Since the pattern of HRQL changes only partly followed the pattern of weight change as expected, other factors, such as the therapeutic effect of participating in the weight loss programme or increase in physical activity, may affect HRQL responses.

Health-related quality of life in obese outpatients losing weight with very-low-energy diet and behaviour modification: a 2-y follow-up study.

To study health-related quality of life (HRQL) in a clinically selected sample obese outpatients. A single-strand before and after study with 2-y follow-up after treatment comprising 10 weeks on very-low-energy diet (VLED) and 4 months of behaviour modification in groups. A total of 126 patients (mean (s.d.) age 48.2 (11.1) y and body mass index (BMI) 42.8 (6.2) kg/m(2) (63% women)) referred for treatment in an obesity clinic. Weight and HRQL using questionnaires (RAND 36-Item Health Survey 1.0 and Obesity-related Psychosocial problems-scale). In all, 100 patients (61% women) completed the treatment and 67 (71% women) completed the 2-y follow-up. The mean (s.d.) weight loss was 12.5 (5.6)% at the end of group therapy, 6.0 (7.1)% at 1 y, and 2.6 (7.5)% at 2 y. At baseline, the mean (s.d.) score for OP-scale was 61.9 (24.6). The mean scores on every RAND-36 scale were markedly lower than in the Finns without chronic conditions. All the scales in HRQL improved markedly during the treatment. During the follow-up, all the scales started to return back towards baseline levels and at 2 y, only obesity-related psychosocial problems and physical functioning were still improved relative to baseline. In categories of weight change at 2 y (> or =10% weight loss, 0-9.9% weight loss, weight gain), obesity-related psychosocial functioning, physical functioning, and general health showed dose-response improvement with increasing weight loss. A > or =10% weight loss at 2 y after treatment was associated with clear improvement in obesity-related psychosocial problems, physical functioning, physical role functioning, bodily pain, general health, mental health, and vitality. A 0-9.9% weight loss was associated with improvement in obesity-related psychosocial problems and physical functioning. Weight gain was associated with improvement in obesity-related psychosocial problems and social functioning. The study population was too small to examine possible gender differences. Treatment with VLED and behaviour modification produces marked short-term weight loss and clear improvement in all aspects of HRQL. At 2 y after treatment, the average maintained weight loss is modest. However, one-third of patients maintain > or =5% weight loss. Improvement in obesity-related psychosocial problems and physical functioning is associated even with &<10% of maintained weight loss. Since the pattern of HRQL changes did only partly follow the pattern of weight change as expected, other factors, such as the therapeutic effect of participating in the weight loss programme or increase in physical activity, may affect HRQL responses.

Long-term weight-loss maintenance: a meta-analysis of US studies

Current perception is that participants of a structured weight-loss program regain all of their weight loss within 5 y. The objective was to examine the long-term weight-loss maintenance of individuals completing a structured weight-loss program. Studies were required to 1) have been conducted in the United States, 2) have included participants in a structured weight-loss program, 3) have provided follow-up data with variance estimates for > or =2 y. Primary outcome variables were weight-loss maintenance in kilograms, weight-loss maintenance as a percentage of initial weight loss, and weight loss as a percentage of initial body weight (reduced weight). Twenty-nine studies met the inclusion criteria. Successful very-low-energy diets (VLEDs) were associated with significantly greater weight-loss maintenance than were successful hypoenergetic balanced diets (HBDs) at all years of follow-up. The percentage of individuals at 4 or 5 y of follow-up for VLEDs and HBDs were 55.4% and 79.7%, respectively. The results for VLEDs and HBDs, respectively, were as follows: weight-loss maintenance, 7.1 kg (95% CI: 6.1, 8.1 kg) and 2.0 (1.5, 2.5) kg; percentage weight-loss maintenance, 29% (25%, 33%) and 17% (13%, 22%); and reduced weight, 6.6% (5.7%, 7.5%) and 2.1% (1.6%, 2.7%). Weight-loss maintenance did not differ significantly between women and men. Six studies reported that groups who exercised more had significantly greater weight-loss maintenance than did those who exercised less. Five years after completing structured weight-loss programs, the average individual maintained a weight loss of >3 kg and a reduced weight of >3% of initial body weight. After VLEDs or weight loss of > or =20 kg, individuals maintained significantly more weight loss than after HBDs or weight losses of <10 kg.

Effect of insulin and energy restriction on the thermic effect of protein in type 2 diabetes mellitus.

The objective of this study was to test whether the thermic effect of oral protein is blunted in poorly controlled type 2 diabetes and is corrected by normalization of glycemia with insulin and 28 days of a very-low-energy diet. Resting energy expenditure (REE) and the thermic effect of 90 g of oral protein were measured, using indirect calorimetry, in nine (five women and four men) obese diabetic people [weight, 108 +/- 10 kg; waist circumference, 123 +/- 8 cm; body mass index, 40 +/- 3 kg/m(2)] who were hyperglycemic on day 8 or euglycemic with insulin on day 16 of a weight-maintaining diet and euglycemic on day 28 of a very low energy diet (VLED). Results were compared with those of seven (six women and one man) weight- and body mass index-matched obese nondiabetic subjects with a waist circumference of 111 +/- 6 cm. Substrates and hormonal responses were determined concurrently. Fasting glucose was normalized in the diabetic subjects with insulin from day 9 of VLED onward. Weight decreased in both groups by 9.9 +/- 0.9 kg with VLED. REE was 8 +/- 2% lower with insulin treatment and decreased by another 14 +/- 3% with VLED in the diabetic and by 15 +/- 1% in the nondiabetic subjects by week 4. After the protein meal, the thermic response was significantly (p < 0.05) less with hyperglycemia than with insulin-induced euglycemia, as percentage above REE (15.3 +/- 1.4 compared with 21.2 +/- 1.5%), as percentage of the energy content of the meal (19.5 +/- 1.5 compared with 25.2 +/- 1.7%), as kilocalories per 405 minutes (86 +/- 5 compared with 110 +/- 7), and less than in nondiabetic obese controls (21.0 +/- 2.2% above REE, 24.4 +/- 1.7% of energy of meal). After the VLED, the thermic effect of protein was significantly higher in both groups only as percentage above REE. The initial glucagon response was greater with hyperglycemia compared with euglycemia and post-VLED but not compared with the nondiabetic subjects. Hyperglycemia was associated with 21 +/- 4% greater urinary urea nitrogen excretion and urinary glucose losses of 134 +/- 50 mmol/d. This study shows a blunted thermic effect of protein in obese hyperglycemic type 2 diabetic subjects compared with matched nondiabetic subjects that can be corrected with insulin- or energy restriction-induced euglycemia.

Very low energy diets in the treatment of obesity.

Very low energy diets (VLEDs) are defined as diets which contain energy levels of less than 3.4 MJ (800 kcal) per day and contain daily allowances of all essential nutritional requirements. These diets have been in clinical use for more than 20 years. They are used as the only source of nutrition for 8-16 weeks, which usually achieves a weight loss of 1.5-2.5 kg per week. Before using this type of diet a medical investigation is necessary to evaluate contraindications and to check medication use during the diet. To facilitate maintenance, cognitive behavioural counselling should always be included in a weight reduction programme using a very low energy diet. VLEDs have no serious harmful effects and can safely be used in patients with various chronic diseases. Programmes using VLEDs produce better short-term weight loss than programmes without the diet. However, in randomized controlled trials VLED-based programmes have not achieved significantly better long-term maintenance than conventional programmes. VLEDs are used when rapid weight loss is necessary because of an obesity-related disease. In other patients with obesity it is an alternative to other conservative approaches for treatment of obesity. In type 2 diabetes it may improve long-term glucose metabolism better than conventional weight reducing diets. Some studies suggest that after a VLED-based programme long-term maintenance is better among men than women. This possible gender difference is an important topic for further research.

Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women

Plasma leptin in humans is subject to both long- and short-term regulation; it correlates with indexes of body fat that can only change slowly. However, short-term fasting causes large and rapid decreases. We tested the interactions between energy intake and fat loss on plasma leptin during prolonged moderate and severe energy restriction, with a view to understanding mechanisms of control. Postabsorptive leptin was measured with an enzyme-linked immunosorbent assay specific for the human peptide in 21 obese women aged 41 +/- 3 y (weight: 102 +/- 4 kg; 48 +/- 1% body fat) after 1 wk of a weight-maintaining diet and then weekly for 4 wk during a total fast (group 1); a 1.9-MJ/d all-protein, very-low-energy diet (VLED) (group 2); or a low-energy, balanced-deficit diet (BDD) providing 50% of maintenance energy (group 3). In groups 1 and 2, leptin was also measured after 1 wk of refeeding with a diet equivalent to the BDD. Mean leptin decreased markedly by up to 66% (P < 0.001) at week 1 of energy restriction and then gradually thereafter. The change in leptin per kilogram fat mass correlated with that in glucose concentrations [r = 0.538 (P = 0.012) at week 1 and r = 0.447 (P = 0.042) at week 4] but not with that in fat mass. During refeeding postfasting, leptin increased (P = 0.008), despite an ongoing loss of fat mass and correlated positively with changes in resting energy expenditure. At times with comparable cumulative energy restriction and fat loss between diets, the percentage change in leptin paralleled that in glucose. In obesity, changes in energy intake over days to weeks are a primary modulator of plasma leptin concentrations that are related to the change in glycemia and are able to override the regulatory influence of fat mass.

Effect of exercise training on long-term weight maintenance in weight-reduced men

This study investigated whether endurance training is effective for successful long-term weight maintenace after weight reduction. Fifteen male obese subjects (age, 37.3 ± 5.2 years; body weight [BW], 96.2 ± 13.6 kg; body mass index [BMI], 30.9 ± 2.8 kg · m −2) participated in a 16-month exercise-intervention study. During the first 4 months, all subjects trained three to four times weekly, consuming a very-low-energy diet (VLED) during the first 2 months. After the 4-month treatment period, seven subjects continued training for 12 months (3 to 4 times per week). The other eight subjects served as a control group not involved in a training program. The regain (increase during the intervention period as a percentage of the 4-month treatment) of BW at 16 months was 64% (±26%) for the whole group (trained v control, 52% ± 28% v 74% ± 20%, P = .09). The increase in absolute fat mass (FM) was significantly lower at 16 months for the trained group (trained v control, 4.8 ± 1.9 v 9.0 ± 3.3 kg), as was the regain of FM at 16 months (trained v control, 61% ± 24% v 92% ± 32%, P = .05). The amount of regain of the waist circumference, waist to hip ratio (WHR), and sagittal diameter were correlated with the amount of training (hours) performed weekly (Δwaist, r = − .55, P < .05; ΔWHR, r =−.50, P = .06; Δsagittal diameter, r = −.53, P < .05). Physical fitness parameters (maximal power output [Wmax] and oxygen uptake [Vo 2 max]) were significantly increased in both groups at 4 months. Trained subjects maintained high levels of physical fitness at 16 months, in contrast to the control group. In conclusion, although BW regain was not significantly different between the groups, trained subjects showed less regain of FM and higher levels of physical fitness, factors related to a lower risk for cardiovascular disease (CVD), compared with the control group. Furthermore, the regain of FM, which occurred even in the exercising group with a relatively intensive training program, suggests that maintenance of fat loss is extremely difficult.

The effect of exercise training on leptin levels in obese males.

The effect of endurance training on plasma leptin levels was investigated in 15 obese male subjects (age 37.3 +/- 5.2 yr, body weight 96.5 +/- 13.6 kg, and body mass index 29.8 +/- 3.0 kg/m2) in a weight loss and exercise program. After 4 mo of treatment consisting of a very low energy diet (VLED) and endurance exercise training (3-4 times weekly, 1 h sessions, moderate intensity), two groups were formed. One group continued the exercise sessions (trained subjects, n = 7) and the other group stopped with the exercise program (control, n = 8). Measurements of anthropometry, aerobic power, and fasted blood samples were executed at fixed time points (0, 2, 4, 10, and 16 mo). With partial regression analysis, keeping the changes in insulin and body fat percentage constant, it was shown that the number of hours of exercise training was significantly correlated with changes in leptin levels, during the 16-mo period (r = 0.56, P < 0.05). Changes in insulin levels were significantly related to the changes in leptin levels (r = 0.47, P < 0.05), which were less for changes in body fat percentage (r = 0.42, P = 0.07). During the VLED, the change in insulin concentration affected leptin levels significantly (r = 0.79) but changes in body fat percentage were not noted. It is concluded that endurance exercise training decreased plasma leptin levels independently of changes in plasma insulin levels and body fat percentage.

Comparison of Behavior Therapy With and Without Very-Low-Energy Diet in the Treatment of Morbid Obesity

Very-low-energy diets (VLEDs) together with behavior therapy (BT) are widely used in the treatment of morbid obesity, but there is no evidence of their long-term effectiveness as compared with behavior therapy alone. Fifty-nine morbidly obese patients (25 men and 34 women; mean weight, 132.8 +/- 20.7 kg; mean age, 43.1 +/- 9.2 years) were treated with combined therapy of VLED and BT or BT alone. No maintenance program was used. Eighty-seven percent of eligible patients were contacted 4.8 to 6.2 years after the program. During treatment, 56% of patients dropped out of the VLED + BT group and 28% from the BT group (P = .03). High scores on the Symptom Checklist-90R before treatment predicted dropout from the VLED+BT group, but not from BT. At the end of therapy, mean weight change was -22.9 kg in the VLED+BT group and -8.9 kg in the BT group (P < .001). The overall weight change from pretreatment to the 5-year follow-up was greater in the VLED+BT group than in the BT group (-16.9 kg vs -4.9 kg, respectively; P = .03). Men succeeded better in the VLED+BT group than in BT. Among the dropouts, the mean weight change from baseline was +5.2 kg in the VLED+BT group and +13.0 kg in the BT group. Our data suggest that in the treatment of morbid obesity, VLED combined with BT may produce a better 5-year maintenance than BT alone, especially among men. A satisfactory weight loss can be achieved without a maintenance program.

Changes in iron status during weight loss with very-low-energy diets

For several decades, very-low-energy diets (VLEDs) have been used by obese individuals to achieve weight loss. During the weight loss, patients often have dramatic drops in circulating thyroid hormone concentrations and experience cold intolerance. Because poor iron status is known to alter thermogenesis, we investigated the possibility that iron intake interacts with energy intake during weight loss in obese individuals. The effects on indicators of iron and thyroid status of increasing the iron content of a VLED from 18 to 27 mg/d during 12 wk of a VLED were compared with the effects on the same indicators of increasing energy intake from 1752 kJ(420 kcal) to 3347 kJ(800 kcal)/d. Although all VLED groups initially had 30% declines in plasma transferrin saturation, increases in plasma ferritin concentrations, and decreases in plasma thyroid hormone concentrations, patients who received iron supplementation had significantly higher circulating concentrations of triiodothyronine and thyroxine at the end of the VLED than did patients who received only the recommended dietary allowance of iron. The patients who received iron supplementation also had a more rapid return of iron indicators to normal values over the course of the VLED. The transitory fall in iron delivery to bone marrow was not associated with anemia. These data suggest that higher thyroid hormone concentrations can be maintained during VLEDs that provide higher iron intakes.

Effect of glycemic control on the kinetics of whole-body protein metabolism in obese subjects with non-insulin-dependent diabetes mellitus during iso- and hypoenergetic feeding

We postulated whether interventions capable of restoring euglycemia would correct whole-body protein metabolism, shown previously to be elevated in hyperglycemic persons with non-insulin-dependent diabetes (NIDDM). The kinetics of protein metabolism were estimated in obese subjects with NIDDM in the hyper- and normoglycemic states during isoenergetic feeding and in the normoglycemic state induced by 4 wk of a very-low-energy diet (VLED) with constant protein intake. Seven NIDDM subjects [three males and four females with a body mass index (in kg/m2) of 39 +/- 2] were given a weight-maintaining, liquid formula providing 95 g protein/d for 15 d, followed in six subjects (two males and four females) for 27 d by a diet providing 1.7 MJ, 93 g protein derived from casein-soy, 13 g carbohydrate, 2 g fat, multivitamins and minerals, and a potassium bicarbonate supplement (32 mmol) per day. Exogenous insulin was given to achieve normoglycemia during the first 8 d of isoenergetic feeding. On days 6-8, 12-14, and 25-27, nitrogen flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain "integrated" feeding and fasting values. Rates of synthesis and breakdown were calculated from nitrogen flux. During isoenergetic feeding, normoglycemia was associated with more positive nitrogen balance (2.6 +/- 0.5 compared with -0.6 +/- 0.6 g N/d, P < 0.05); 18-23% lower nitrogen flux, and synthesis and breakdown rates (P < 0.05), and a 3% decrease in resting energy expenditure (P < 0.05). During the VLED, euglycemia was achieved but nitrogen balance, although it became less negative with time, never reached equilibrium. This was associated with significant (P < 0.05) decreases in the synthesis rate, resulting in net protein losses. Thus, the altered protein metabolism in moderately hyperglycemic NIDDM subjects was improved with exogenous insulin in doses sufficient to restore normoglycemia in the isoenergetic fed state, but it remained abnormal with a reduced non-protein energy intake. This suggests that protein metabolism is more sensitive to insulinization than was thought previously.

Thermic and metabolic responses to oral glucose in obese subjects with non-insulin-dependent diabetes mellitus treated with insulin or a very-low-energy diet

Increased resting energy expenditure (REE) and a blunted thermic effect of glucose (TEF) have been reported in obese subjects with non-insulin-dependent diabetes mellitus (NIDDM). I questioned whether the abnormal REE and TEF would be corrected by normalizing glycemia with insulin or a very-low-energy diet (VLED). Three male and four female obese subjects with NIDDM [weighing 108 +/- 6 kg and with body mass index (in kg/m2) of 39 +/- 2] received a weight-maintaing formula diet containing 95 g protein/d for 15 d then a 1.7-MJ, 93-g-protein VLED for 27 d. Insulin was given from days 1 to 8 in doses sufficient to normalize glycemia. REE was measured weekly and TEF was measured on days 8 and 15 of isoenergetic feeding and 28 d after the VLED by using a ventilated-hood indirect calorimeter. Weight decreased 9.8 +/- 1 kg during the VLED. REE was 3% lower with insulin treatment than during hyperglycemia (7878 +/- 364 compared with 8125 +/- 381 kJ/d, P = 0.002). REE decreased by 20% to 6494 +/- 280 kJ/d by week 4 of the VLED. After 112 g oral glucose, increments in energy expenditure were significantly greater during isoenergetic feeding with insulin than without (7.5 +/- 1.3% compared with 4.3 +/- 0.9% above REE) and after the VLED (10.5 +/- 1.0% above REE, P < 0.05). Plasma glucose excursions were greatest without exogenous insulin (peak 21.5 +/- 1.8 mmol/L at 120 min, 16.3 +/- 1.9 mmol/L at 225 min). Plasma fatty acid excursions were the lowest with insulin treatment. The integrated plasma glucose and fatty acid responses above baseline did not differ among studies; the integrated insulin and C-peptide responses were greater after the VLED. Cumulative nonoxidative glucose disposal (stored glucose) was higher with insulin therapy than without (52 +/- 6 compared with 35 +/- 7 g/210 min, P < 0.05) and increased significantly to 66 +/- 6 g after the VLED (compared with the isoenergetic diet without insulin). TEF correlated significantly with integrated C-peptide and insulin responses. The percentage increase in TEF with euglycemia (with insulin and VLED) correlated with the percentage increase in stored glucose (P < 0.05). The greater TEF was associated with a greater insulin response, which was probably responsible for the greater stored glucose.