W. H. M. Saris

The Diet, Obesity and Genes (Diogenes) Dietary Study in eight European countries – a comprehensive design for long-term intervention

Diogenes is a Pan‐European, randomized, controlled dietary intervention study investigating the effects of dietary protein and glycaemic index on weight (re)gain, metabolic and cardiovascular risk factors in obese and overweight families in eight European centres. The article is methodological in character, and the presentation of ‘results’ will be limited to baseline characteristics of the study populations included. A total of 891 families with at least one overweight/obese parent underwent screening. The parents started an initial 8‐week low‐calorie diet and families with minimum one parent attaining a weight loss of ≥8%, were randomized to one of five energy ad libitum, low‐fat (25–30 E%) diets for 6 or 12 months: low protein/low glycaemic index, low protein/high glycaemic index, high protein/low glycaemic index, high protein/high glycaemic index or control (national dietary guidelines). At two centres the families were provided dietary instruction plus free foods for 6 months followed by 6‐month dietary instruction only. At the remaining six centres the families received dietary instruction only for 6 months. The median weight loss during the low‐calorie diet was 10.3 kg (inter‐quartile range: 8.7–12.8 kg, n = 775). A total of 773 adults and 784 children were randomized to the 6‐month weight (re)gain prevention phase. Despite major cultural and dietary regional differences in Europe, interventions addressing effects of dietary factors are feasible with a reasonable attrition.

Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance.

1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched‐chain amino acids (BCAAs) affect performance. Ten endurance‐trained male athletes were studied during cycle exercise at 70‐75% maximal power output, while ingesting, ad random and double‐blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l‐1), (2) a low dose of BCAA (6 g l‐1) or (3) a high dose of BCAA (18 g l‐1). 2. These treatments greatly increased the plasma concentration of the respective amino acids. Using the kinetic parameters of transport of human brain capillaries, BCAA supplements were estimated to reduce brain tryptophan uptake at exhaustion by 8‐12%, while tryptophan ingestion caused a 7‐ to 20‐fold increase. Exercise time to exhaustion was not different between treatments (122 +/‐ 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise or that manipulation of serotoninergic activity functionally does not contribute to mechanisms of fatigue.

Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle

Lipotoxicity in skeletal muscle plays a critical role in the aetiology of insulin resistance and type 2 diabetes mellitus by interference of lipid metabolites with insulin signalling and action. The dynamics of lipid oxidation and fine tuning with fatty acid uptake and intramyocellular triacylglycerol turnover may be very important to limit the accumulation of lipid intermediates. The use of metabolic inflexibility, defined as the impaired capacity to increase fat oxidation upon increased fatty acid availability and to switch between fat and glucose as the primary fuel source after a meal, does more justice to the complexity of changes in fuel oxidation during the day. Fatty acid availability, uptake and oxidation all play a role in metabolic flexibility and insulin resistance. During high fatty acid availability, fatty acid transporters may limit cellular and mitochondrial fatty acid uptake and thus limit fat oxidation. After a meal, when the demand for fatty acids as fuel is low, an increased fractional extraction of lipids from plasma may promote intramyocellular lipid accumulation and insulin resistance. Furthermore, defects in fuel switching cluster together with impaired mitochondrial content and/or function. Lifestyle changes in dietary fat intake, physical activity and weight loss may improve metabolic flexibility in skeletal muscle, and thereby contribute to the prevention of type 2 diabetes.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.

Background:Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective:This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design:A free-living, single-blinded dietary intervention study.Subjects and Methods:MetS subjects (n=417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results:In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P<0.01), particularly in men.Conclusion:There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Determinants of weight maintenance in women after diet-induced weight reduction.

OBJECTIVE: Assessment of determinants for relatively successful weight maintenance in women after diet-induced weight reduction.DESIGN: Subjects followed two weight cycles over two years, each cycle starting with a Very Low Energy Diet (VLED) (2.8 MJ/d), in a free-living situation. They completed the Herman Polivy Restraint Questionnaire and the Three Factor Eating Questionnaire twice, that is, before and during the first VLED.SUBJECTS: Twenty seven obese women, body mass index (BMI) (28–38 kg/m2), age (19–53 y), being premenopausal and healthy, participated twice in the energy restriction periods with one year follow-up.MEASUREMENTS: Weight and body composition were measured at weeks 0, 8, 60, 68 and 120 after the start of the first VLED. Scores on the restraint scales before and during the first VLED were analysed. Percentages regain after one year and after two years follow-up were related to these scores.RESULTS: Three groups appeared with respect to success regarding weight maintenance. Group 1 (successful): twice a regain <50% of weight loss; group 2 (partly successful): once a regain <50% of weight loss and group 3 (unsuccessful): twice a regain of >50% of weight loss. Percentage regain was negatively correlated to an increase in cognitive restrained eating behaviour (r=0.8; P=0.0001). A change in attitude with respect to food intake, expressed as an increase in cognitive restraint, and as a positive relationship between cognitive restraint and disinhibition was related to successful weight maintenance.CONCLUSION: An increase in cognitive restraint from before, to during, the diet, and a positive correlation between cognitive restraint and disinhibition, are two determinants representing eating behaviour for successful weight maintenance.

Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults

Introduction:Mechanisms for liraglutide-induced weight loss are poorly understood.Objective:We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals.Design:Participants (N=49, 18–75 years, body mass index: 30–40 kg m−2) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed.Results:Five-hour gastric emptying (AUC0–300 min) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80–1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5–0.6 mmol l−1 versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC0–300 min (by ∼26% versus placebo, P=0.02). Glucagon iAUC0–300 min decreased by ∼30%, and iAUC0–60 min for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk.Conclusion:Gastric emptying AUC0–300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects after weight loss on weight regain, body composition, resting metabolic rate, substrate oxidation, and blood plasma parameters.DESIGN: This study had a double-blind, placebo-controlled randomized design. Subjects were first submitted to a very-low-calorie diet (VLCD 2.1 MJ/d) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day (low dosage, LD) or 3.6 g CLA or placebo per day (high dosage, HD).SUBJECTS: A total of 26 men and 28 women (age 37.8±7.7 y; body mass index (BMI) 27.8±1.5 kg/m2).MEASUREMENTS: Before VLCD (t=−3), after VLCD but before CLA or placebo intervention (t=0) and after 13-week CLA or placebo intervention (t=13), body weight, body composition (hydrodensitometry and deuterium dilution), resting metabolic rate, substrate oxidation, physical activity, and blood plasma parameters (glucose, insulin, triacylglycerol, free fatty acids, glycerol and β-hydroxy butyrate) were measured.RESULTS: The VLCD significantly lowered body weight (6.9±1.7%), %body fat, fat mass, fat-free mass, resting metabolic rate, respiratory quotient and plasma glucose, insulin, and triacylglycerol concentrations, while free fatty acids, glycerol and β-hydroxy butyrate concentrations were increased. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not affect %body weight regain (CLA LD 47.9±88.2%, CLA HD 27.4±29.8%, Placebo LD 32.0±42.8%, Placebo HD 22.5±37.9%). The regain of fat-free mass was increased by CLA (LD 6.2±3.9, HD 4.6±2.4%) compared to placebo (LD 2.8±3.2%, HD 3.4±3.6%), independent of %body weight regain and physical activity. As a consequence of an increased regain of fat-free mass by CLA, resting metabolic rate was increased by CLA (LD 12.0±11.4%, HD 13.7±14.4%) compared to placebo (LD 9.1±11.0%, HD 8.6±8.5%). Substrate oxidation and blood plasma parameters were not affected by CLA.CONCLUSION: In conclusion, the regain of fat-free mass was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day and consequently increased the resting metabolic rate. However, it did not result in improved body weight maintenance after weight loss.

Daily physical activity of schoolchildren with spastic diplegia and of healthy control subjects

OBJECTIVE To assess the differences in daily physical activity between children with spastic diplegia and healthy schoolchildren, to determine whether special physical activity programs are needed in the population with cerebral palsy. DESIGN Cross-sectional design. SETTING Childrens rehabilitation center Franciscusoord (day care center) and elementary schools. SUBJECTS Children with spastic diplegia (5 boys; mean (+/- SD) age 8.0 +/- 1.4 years; 9 ambulant, 1 wheelchair use) and healthy children (5 boys; mean (+/- SD) age 8.4 +/- 1.0 years). MEASUREMENTS Total daily energy expenditure (TEE) and sleeping metabolic rate (SMR) were measured by the doubly labeled water technique and a respiration chamber. The TEE/SMR ratio was used as an index for the level of daily physical activity. RESULTS The TEE/SMR ratio under normal daily conditions in the children with cerebral palsy (mean +/- SD): 1.56 +/- 0.19) was significantly lower (p < 0.05) than in their healthy peers (mean +/- SD: 1.83 +/- 0.23) and was similar to the TEE/SMR ratio in a room-sized chamber. CONCLUSION Children with spastic diplegia are considerably less active than their healthy peers. We recommend special physical activity programs for these children.

The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors.

Background:High-protein (HP) diets are often advocated for weight reduction and weight loss maintenance.Objective:The aim was to compare the effect of low-fat, high-carbohydrate (HC) and low-fat, HP ad libitum diets on weight maintenance after weight loss induced by a very low-calorie diet, and on metabolic and cardiovascular risk factors in healthy obese subjects.Design:Forty-eight subjects completed the study that consisted of an energy restriction period of 5–6 weeks followed by a weight maintenance period of 12 weeks. During weight maintenance subjects received maltodextrin (HC group) or protein (HP group) (casein (HPC subgroup) or whey (HPW subgroup)) supplements (2 × 25 g per day), respectively and consumed a low-fat diet.Results:Subjects in the HP diet group showed significantly better weight maintenance after weight loss (2.3 kg difference, P=0.04) and fat mass reduction (2.2 kg difference, P=0.02) than subjects in the HC group. Triglyceride (0.6 mM difference, P=0.01) and glucagon (9.6 pg ml−1 difference, P=0.02) concentrations increased more in the HC diet group, while glucose (0.3 mM difference, P=0.02) concentration increased more in the HP diet group. Changes in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, insulin, HOMAir index, HbA1c, leptin and adiponectin concentrations did not differ between the diets. No differences were found between the casein- or whey-supplemented HP groups.Conclusions:These results show that low-fat, high-casein or whey protein weight maintenance diets are more effective for weight control than low-fat, HC diets and do not adversely affect metabolic and cardiovascular risk factors in weight-reduced moderately obese subjects without metabolic or cardiovascular complications.

Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year

AIMS: Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity, diet and physical inactivity. The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance (IGT).METHODS: A total of 102 subjects were studied, randomised into two groups. Subjects in the intervention group received regular dietary advice, and were stimulated to lose weight and to increase their physical activity. The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity. Before and after the first year, glucose tolerance was measured and several other measurements were done.RESULTS: Body weight loss after 1 y was higher in the intervention group. The 2-h blood glucose concentration decreased 0.8±0.3 mmol/l in the intervention group and increased 0.2±0.3 mmol/l in the control group (P<0.05). Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity.CONCLUSION: A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle, which improve glucose tolerance in subjects with IGT. Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity.