The PREVIEW intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes.

AIM: To compare the impact of two long-term weight-maintenance diets, a high protein (HP) and low glycaemic index (GI) diet versus a moderate protein (MP) and moderate GI diet, combined with either high intensity (HI) or moderate intensity physical activity (PA), on the incidence of type 2 diabetes (T2D) after rapid weight loss. MATERIALS AND METHODS: A 3-year multicentre randomized trial in eight countries using a 2 x 2 diet-by-PA factorial design was conducted. Eight-week weight reduction was followed by a 3-year randomized weight-maintenance phase. In total, 2326 adults (age 25-70 years, body mass index ≥ 25 kg/m2 ) with prediabetes were enrolled. The primary endpoint was 3-year incidence of T2D analysed by diet treatment. Secondary outcomes included glucose, insulin, HbA1c and body weight. RESULTS: The total number of T2D cases was 62 and the cumulative incidence rate was 3.1%, with no significant differences between the two diets, PA or their combination. T2D incidence was similar across intervention centres, irrespective of attrition. Significantly fewer participants achieved normoglycaemia in the HP compared with the MP group (P < .0001). At 3 years, normoglycaemia was lowest in HP-HI (11.9%) compared with the other three groups (20.0%-21.0%, P < .05). There were no group differences in body weight change (-11% after 8-week weight reduction; -5% after 3-year weight maintenance) or in other secondary outcomes. CONCLUSIONS: Three-year incidence of T2D was much lower than predicted and did not differ between diets, PA or their combination. Maintaining the target intakes of protein and GI over 3 years was difficult, but the overall protocol combining weight loss, healthy eating and PA was successful in markedly reducing the risk of T2D. This is an important clinically relevant outcome.

Preliminary evidence that endoscopic gastroplication reduces food reward.

Morbidly obese patients are most successfully treated with bariatric surgery. Although restrictive gastric surgery physically limits food intake, it is also suggested that eating behavior and food-reward mechanisms are affected. Therefore, eating behavior and food-reward were assessed in ten patients that underwent gastric volume reduction by endoscopic gastroplication. Patients participated in test days before and one, three and twelve months after the procedure. Weight loss, food intake, appetite, gastric emptying rate, food-reward (i.e. liking and wanting) and eating behavior were assessed. Body mass index decreased from 38.3 (37.6-42.6) to 33.9 (31.0-35.9) kg/m2 after one year. Ad libitum food intake decreased significantly after one month, but not after one year. Gastric emptying rate did not change. AUC of VAS scores for desire to eat, quantity, fullness, hunger, snacking and satiety changed after one month, but not all remained significantly changed after one year. Thirst did not change. Liking scores of food items decreased significantly in the fasted as well as the satiated state after the procedure. Wanting scores did not change. Uncontrolled eating decreased significantly after three and twelve months; emotional eating was only significantly decreased after three months. The results show that food intake decreases, while VAS scores for appetite and eating behavior change accordingly. Liking, but not wanting of food items changed to benefit the weight losing patient. The effects were stronger at one-month follow-up than at 12 months, which may be a risk of relapse after initial successful weight loss. The effects of new bariatric procedures on food-reward should be studied in future randomized trials to further elucidate their impact. REGISTERED AT CLINICALTRIALS. GOV: NCT02381340.

Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (-56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = -0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

Capsaicin increases sensation of fullness in energy balance, and decreases desire to eat after dinner in negative energy balance.

Addition of capsaicin (CAPS) to the diet has been shown to increase satiety; therefore, CAPS is of interest for anti-obesity therapy. We investigated the effects of CAPS on appetite profile and ad libitum energy intake in relation to energy balance. Fifteen subjects (seven women and eight men, age: 29.7 ± 10.8yrs, BMI: 23.3 ± 2.9 kg/m(2)) underwent four conditions in a randomized crossover design in 36 hour sessions in a respiration chamber; they received 100% of their daily energy requirements in the conditions "100%Control" and "100%CAPS", and 75% of their daily energy requirements in the conditions "75%Control" and "75%CAPS", followed by an ad libitum dinner. In the 100%CAPS and 75%CAPS conditions, CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units) with every meal. Satiety (P < 0.05) and fullness (P = 0.01) were measured every waking hour and before and after every meal using visual analogue scales, and were higher in the 100%CAPS versus 100%Control condition. After dinner desire to eat, satiety and fullness did not differ between 75%CAPS and 100%Control, while desire to eat was higher (P < 0.05) and satiety (P = 0.06) and fullness (P = 0.06) tended to be lower in the 75%Control versus 100%Control condition. Furthermore, ad libitum intake (P = 0.07) and overconsumption (P = 0.06) tended to decrease in 100%CAPS versus 100%Control. In energy balance, addition of capsaicin to the diet increases satiety and fullness, and tends to prevent overeating when food intake is ad libitum. After dinner, capsaicin prevents the effects of the negative energy balance on desire to eat.

Catechin- and caffeine-rich teas for control of body weight in humans.

Maintaining the level of daily energy expenditure during weight loss and weight maintenance is as important as maintaining satiety while decreasing energy intake. In this context, different catechin- and caffeine-rich teas (CCRTs), such as green, oolong, and white teas, as well as caffeine have been proposed as tools for maintaining or enhancing energy expenditure and for increasing fat oxidation. Tea polyphenols have been proposed to counteract the decrease in metabolic rate that is usually present during weight loss. Their effects may be of particular importance during weight maintenance after weight loss. Although the thermogenic effect of CCRT has the potential to produce significant effects on these metabolic targets as well as on fat absorption and energy intake, possibly via its impact on the gut microbiota and gene expression, a clinically meaningful outcome also depends on compliance by the subjects. Limitations to this approach require further examination, including moderating factors such as genetic predisposition, habitual caffeine intake, and catechin composition and dose. Nevertheless, CCRTs may be useful agents that could help in preventing a positive energy balance and obesity.

Satiating capacity and post-prandial relationships between appetite parameters and gut-peptide concentrations with solid and liquefied carbohydrate.

BACKGROUND: Differences in satiating capacity of liquid and solid meals are unclear. OBJECTIVE: Investigating appetite parameters, physiological measurements and within-subject relationships after consumption of a single macronutrient, subject-specific carbohydrate meal in liquefied versus solid form, controlled for energy density, weight and volume. DESIGN: In a cross-over design, ten male subjects (age = 21.1±3.9 y, BMI = 22.4±1.2 kg/m(2)) consumed a solid (CS, whole peaches +750 ml water) and liquefied carbohydrate (CL, peach blended in 500 ml water +250 ml water) lunch. Appetite profiles, insulin-, glucose- and ghrelin concentrations were measured over three hours. Post-prandial relationships between appetite and blood parameters were calculated using subject-specific regression analyses. RESULTS: Fullness ratings were higher in the CL (85±5 mm) compared to the CS condition (73±8 mm) at 20 min (p<0.03). Glucose concentrations peaked 20 to 30 min after the start of the lunch in the CL condition, and 30 to 40 min after start of the CS condition. Correspondingly, insulin concentrations were peaked at 20-30 min in the CL condition, and at 30-40 min in the CS condition. AUC or condition x time interactions were not different comparing the CL and the CS condition. Insulin was significantly higher in the CS compared to the CL condition 40 min after the start of the lunch (p<0.05). Fullness scores were significantly related to insulin concentrations but not to glucose concentrations; desire to eat scores were significantly associated with ghrelin concentrations in both, the CL and the CS condition. The relationship between fullness scores and glucose concentrations was not statistically significant. CONCLUSION: Liquefied and solid carbohydrate meals do not differ in satiating capacity, supported by appetite profile and relevant blood parameters. Postprandially, fullness and desire to eat were associated with respectively insulin and ghrelin concentrations.

Effects of sleep fragmentation in healthy men on energy expenditure, substrate oxidation, physical activity, and exhaustion measured over 48 h in a respiratory chamber.

BACKGROUND: Epidemiologic studies show an inverse or U-shaped relation between sleep duration and BMI. Decreases in total energy expenditure (TEE) and physical activity have been suggested to be contributing factors. OBJECTIVE: The objective was to assess the effect of sleep fragmentation on energy metabolism and energy balance in healthy men. DESIGN: Fifteen healthy male subjects [mean ± SD BMI (in kg/m(2)): 24.1 ± 1.9; age: 23.7 ± 3.5 y] were included in a randomized crossover study in which energy expenditure, substrate oxidation, and physical activity (by radar) were measured twice for 48 h in a respiration chamber while subjects were monitored by electroencephalography to determine slow-wave sleep (SWS), rapid eye movement (REM) sleep, and total sleeping time (TST). During 2 nights, sleep (2330-0730 h) was either fragmented or nonfragmented. RESULTS: Fragmented sleep led to reductions in TST, SWS, and REM sleep (P < 0.001). TEE did not differ (9.96 ± 0.17 compared with 9.83 ± 0.13 MJ/d, NS) between the sleep groups, nor did the components of energy expenditure, with the exception of activity-induced energy expenditure (AEE; 1.63 ± 0.15 compared with 1.42 ± 0.13 MJ/d for fragmented and nonfragmented sleep, respectively; P < 0.05). Physical activity, exhaustion, sleepiness, respiratory quotient (RQ), and carbohydrate oxidation were elevated in comparison with nonfragmented sleep [physical activity counts: 2371 ± 118 compared with 2204 ± 124 counts/d, P < 0.02; exhaustion: 40.1 ± 3.8 compared with 21.8 ± 2.4 mm (by using a visual analog scale; VAS), P < 0.001; sleepiness: 47.4 ± 4.2 compared with 33.9 ± 4.6 mm (VAS), P < 0.001; RQ: 0.94 ± 0.04 compared with 0.91 ± 0.03, P < 0.05; and carbohydrate oxidation: 346.3 ± 23.8 compared with 323.7 ± 22.5 g/d, P < 0.05], whereas fat oxidation was reduced (29.1 ± 9.1 compared with 61.0 ± 6.6 g/d, P < 0.01). CONCLUSIONS: Fragmented compared with nonfragmented sleep induced reductions in the most important sleep phases, which coincided with elevated AEE, physical activity, exhaustion, and sleepiness. RQ and carbohydrate oxidation increased and fat oxidation decreased, which may predispose to overweight. This trial is registered at www.who.int/ictrp and www.trialregister.nl as NTR1919.

Consumption of milk-protein combined with green tea modulates diet-induced thermogenesis.

Green tea and protein separately are able to increase diet-induced thermogenesis. Although their effects on long-term weight-maintenance were present separately, they were not additive. Therefore, the effect of milk-protein (MP) in combination with green tea on diet-induced thermogenesis (DIT) was examined in 18 subjects (aged 18-60 years; BMI: 23.0 ± 2.1 kg/m(2)). They participated in an experiment with a randomized, 6 arms, crossover design, where energy expenditure and respiratory quotient (RQ) were measured. Green tea (GT)vs. placebo (PL) capsules were either given in combination with water or with breakfasts containing milk protein in two different dosages: 15 g (15 MP) (energy% P/C/F: 15/47/38; 1.7 MJ/500 mL), and 3.5 g (3.5 MP) (energy% P/C/F: 41/59/0; 146.4 kJ/100 mL). After measuring resting energy expenditure (REE) for 30 min, diet-induced energy expenditure was measured for another 3.5 h after the intervention. There was an overall significant difference observed between conditions (p < 0.001). Post-hoc, areas under the curve (AUCs) for diet-induced energy expenditure were significantly different (P ≤ 0.001) for GT + water (41.11 [91.72] kJ·3.5 h) vs. PL + water (10.86 [28.13] kJ·3.5 h), GT + 3.5 MP (10.14 [54.59] kJ·3.5 h) and PL + 3.5 MP (12.03 [34.09] kJ·3.5 h), but not between GT + 3.5 MP, PL + 3.5 MP and PL + water, indicating that MP inhibited DIT following GT. DIT after GT + 15 MP (167.69 [141.56] kJ·3.5 h) and PL + 15 MP (168.99 [186.56] kJ·3.5 h) was significantly increased vs. PL + water (P < 0.001), but these were not different from each other indicating that 15 g MP stimulated DIT, but inhibited the GT effect on DIT. No significant differences in RQ were seen between conditions for baseline and post-treatment. In conclusion, consumption of milk-protein inhibits the effect of green tea on DIT.

Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on energy intake and satiety.

AIM: To compare the effects of whey versus whey without glycomacropeptide (GMP) in a high and a normal amount of protein in a breakfast custard on satiety and energy intake (EI), taking concentrations of amino acids (AA), glucose, insulin, glucagon-like peptide 1 (GLP-1) and ghrelin into account. METHODS: Twenty-five healthy subjects (mean+/-S.E.M., BMI: 23.9+/-0.3 kg/m(2); age: 22+/-1 years) received a breakfast containing whey or whey without GMP as protein type with 10/55/35 or 25/55/20 En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scale, VAS), glucose, insulin, GLP-1, ghrelin and AA concentrations were measured, and the adequate moment for ad libitum lunch was determined based on differences in ghrelin concentration. In a second set of experiments subjects received the same breakfasts; ad libitum lunch was offered at the pre-determined moment. RESULTS: After a breakfast with 25 En% protein increases in insulin and GLP-1 and decreases in ghrelin concentrations were larger; increases in satiety ratings were lower than after 10 En% (p<0.05); there was a treatment x time interaction effect on glucose and insulin concentrations (p<0.001). After a breakfast with whey without GMP insulin concentrations were increased more than after whey (p<0.05). EI at lunch was lower after whey than after whey without GMP (2877+/-165 kJ versus 3208+/-178 kJ, p<0.05), coinciding with more increased concentrations of serine, threonine, alanine, alpha-aminobutyric acid and isoleucine (p<0.05). CONCLUSION: GMP as a whey-fraction reduced energy intake coinciding with increased concentrations of certain amino acids, irrespective of the concentration of whey-protein. Although between different concentrations of whey-protein differences in hormone responses were observed, these were unrelated to satiety ratings or energy intake.

Somatotropic responses to soy protein alone and as part of a meal.

CONTEXT: GH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal. OBJECTIVE/DESIGN: We compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19-26 kg/m(2), 19-36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min. RESULTS: GH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05). CONCLUSION: The somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.

Effects of very low calorie diet induced body weight loss with or without human pegylated recombinant leptin treatment on changes in ghrelin and adiponectin concentrations.

The aim of the study was to investigate the effects of energy restriction with or without pegylated recombinant leptin (PEG-leptin) treatment on ghrelin, adiponectin, insulin and glucose concentrations. A randomized double-blind placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG-leptin or placebo was administered weekly for 6 weeks, combined with a restricted energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and body-weight (BW) was measured. Days 1-25 was named phase 1, and days 25-46 phase 2. During phase 1 the rate of BW loss was significantly higher in the PEG-leptin compared to the placebo group (0.38+/-0.07 vs 0.32+/-0.06 kg/d, p<0.05). The rate of BW loss during phase 2 was 0.24+/-0.08 and 0.18+/-0.09 kg/d, respectively (p=0.07). In both groups the rate of BW loss during phase 1 was significantly higher than during phase 2 (p<0.001). Energy balance (EB) was significantly more negative during phase 1 than during phase 2 in both groups (p<0.0005). During phase 1 insulin, glucose and adiponectin decreased significantly in both groups. Adiponectin and ghrelin concentrations changed in the opposite direction between phase 1 and phase 2 (p<0.05). Initial BW loss due to a considerable negative EB induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when EB became less negative and the rate of BW loss decreased, these changes were reversed for adiponectin and ghrelin. The PEG-leptin injections did not have an effect on the changes in insulin, glucose and adiponectin, but had an effect on the changes in ghrelin concentrations.

Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber.

BACKGROUND: The mechanism of protein-induced satiety remains unclear. OBJECTIVE: The objective was to investigate 24-h satiety and related hormones and energy and substrate metabolism during a high-protein (HP) diet in a respiration chamber. DESIGN: Twelve healthy women aged 18-40 y were fed in energy balance an adequate-protein (AP: 10%, 60%, and 30% of energy from protein, carbohydrate, and fat, respectively) or an HP (30%, 40%, and 30% of energy from protein, carbohydrate, and fat, respectively) diet in a randomized crossover design. Substrate oxidation, 24-h energy expenditure (EE), appetite profile, and ghrelin and glucagon-like peptide 1 (GLP-1) concentrations were measured. RESULTS: Sleeping metabolic rate (6.40 +/- 0.47 compared with 6.12 +/- 0.40 MJ/d; P < 0.05), diet-induced thermogenesis (0.91 +/- 0.25 compared with 0.69 +/- 0.24 MJ/d; P < 0.05), and satiety were significantly higher, and activity-induced EE (1.68 +/- 0.32 compared with 1.86 +/- 0.41; P < 0.05), respiratory quotient (0.84 +/- 0.02 compared with 0.88 +/- 0.03; P < 0.0005), and hunger were significantly lower during the HP diet. There was a tendency for a greater 24-h EE during the HP diet (P = 0.05). Although energy intake was not significantly different between the diet groups, the subjects were in energy balance during the HP diet and in positive energy balance during the AP diet. Satiety was related to 24-h protein intake (r2 = 0.49, P < 0.05) only during the HP diet. Ghrelin concentrations were not significantly different between diets. GLP-1 concentrations after dinner were higher during the HP than during the AP diet (P < 0.05). CONCLUSION: An HP diet, compared with an AP diet, fed at energy balance for 4 d increased 24-h satiety, thermogenesis, sleeping metabolic rate, protein balance, and fat oxidation. Satiety was related to protein intake, and incidentally to ghrelin and GLP-1 concentrations, only during the HP diet.

The utility of animal models of human energy homeostasis.

The prevalence of obesity among adults and children has increased steadily over the last few years worldwide, reaching epidemic proportions. Particularly alarming is the link between obesity and the development of chronic disorders such as heart disease, type 2 diabetes, hypertension and some cancers (Bjorntorp, 1997). Environmental causes of obesity are thought to include a sedentary lifestyle and an abundance of highly palatable energy-dense foods (Hill et al. 2003). Genetic factors also contribute to susceptibility to obesity, although the genetic basis of most human obesities is thought to be polygenic (Comuzzie & Allison, 1998; Barsh et al. 2000). The present paper considers some of the animal models used to infer aspects of human obesity, with an emphasis upon their usefulness.

Leptin and the proinflammatory state associated with human obesity.

It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.

The effect of addition of linoleic acid on food intake regulation in linoleic acid tasters and linoleic acid non-tasters.

In a randomised, single blind, placebo-controlled crossover design study, we investigated whether healthy, non-smoking, dietary unrestrained women (n 24), divided into linoleic acid tasters (LAT, n 14) and linoleic acid non-tasters (LANT, n 10), differed in food intake regulation when linoleic acid was added to ice creams. The determination of subjects as LAT or LANT was done using a 10 microm-linoleic acid solution. The ice creams were characterised by the subjects and a taste perception test using the triangle test was conducted three times. Food intake and appetite were measured using the universal eating monitor. LAT and LANT did not differ in characterisation or in taste perception of the ice creams, even though LAT were able to increase their ability to discriminate between the ice cream with linoleic acid from the one containing oleic acid. No effect of LAT status or type of ice cream was found for hedonic value of the ice creams. Linoleic acid taster status did affect food intake regulation. For LAT, but not LANT, the amount eaten was a function of Deltasatiety. Subjects ate by weight of food and not by energy content. In conclusion, differences in food intake regulation were seen between LAT and LANT, in that the amount eaten by LAT was a function of Deltasatiety, but was not for LANT.