Marie Kunesova

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.

Intrapair resemblance in very low calorie diet- induced weight loss in female obese identical twins

OBJECTIVE: To assess intrapair resemblance in changes of body weight, total body fat, fat distribution, resting metabolic rate, fasting respiratory quotient and cardiovascular disease risk factors in response to therapeutic weight loss in female obese identical twins.DESIGN: Patients stayed for 40 days on an inpatient metabolic unit under careful supervision. The stay was divided into three parts: an initial period of 7 days for adjustment to the hospital environment and for baseline measurements, 28 days of the weight reduction regimen when negative energy balance was achieved mainly by a very low calorie diet (1.6 MJ per day) and 5 days of testing after weight reduction.SUBJECTS: Fourteen pairs of premenopausal female obese identical twins (age: 39.0±1.7 y; body weight (BW): 93.9±21.2 kg; body mass index (BMI): 34.2±7.8 kg/m2) participated in the study.MEASUREMENTS:. Before and after weight loss, the following measurements were made: body composition by anthropometry and hydrodensitometry, intra-abdominal fat by ultrasonography, resting metabolic rate by indirect calorimetry. Total cholesterol, high-density lipoprotein-cholesterol, triglycerides and uric acid were determined by standard laboratory procedures. Blood pressure was measured in the morning in the recumbent position.RESULTS: Subjects lost 8.8±1.9 kg of weight, from 93.9±21.2 to 85.1±10.9 kg (P<0.0001) and 6.5±2.3 kg of body fat (P<0.001). Weight losses varied widely among subjects, with a high correlation between losses of members of twin pairs for body weight (r=0.85; P<0.001) and for body fat (r=0.88; P<0.0001). Changes in uric acid resulting from weight loss were also correlated among members of twin pairs whereas changes in blood pressure, cholesterol and triglycerides were not.CONCLUSION: The great intrapair resemblance observed in very low calorie diet-induced weight and fat losses in female obese identical twins suggests an important role of genetic factors in response to the weight reduction regimen.

Serotonin and Norepinephrine Reuptake Inhibition and Eating Behavior

Abstract:  Brain neurotransmitters, serotonin and norepinephrine, play an important role in the central nervous control of energy balance and are involved in symptomatology related to both obesity and depression. Therefore both serotonin and norepinephrine neural pathways have been paid a special attention as targets for the antiobesity drugs, antidepressants, and drugs used in the treatment of eating disorders. Selective serotonin reuptake inhibitors (SSRI) have been used in the treatment of depression and eating disorders but have failed to achieve sustained weight loss in the treatment of obesity. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, which induces satiety and prevents decline in metabolic rate associated with a hypocaloric diet, is currently the sole centrally acting drug indicated for the long‐term treatment of obesity. Depression, dietary disinhibition (evaluated by the Eating Inventory [EI]), and stress are associated with the accumulation of abdominal fat and the development of metabolic syndrome and related diseases. Subjects with abdominal obesity demonstrate neuroendocrine abnormalities which result in disturbances in hypothalamo‐pituitary‐adrenal (HPA) function. Treatment with SSRI might interrupt the vicious circle which leads to endocrine abnormalities and the accumulation of abdominal fat. Obesity treatment with sibutramine results, not only in significant weight loss, but also in reduction of abdominal fat and in the improvement of health risks associated with metabolic syndrome (lipid profile, blood glucose, insulin, HbA1c, and uric acid), as well as in the decline in disinhibition score of the EI. In a 1‐year sibutramine trial, only a decrease in the disinhibition score remained a significant correlate of weight loss among the psychobehavioral and nutritional factors which were taken into account.

The Effect of Protein and Glycemic Index on Children's Body Composition: The DiOGenes Randomized Study

OBJECTIVE: To investigate the effect of protein and glycemic index (GI) on body composition among European children in the randomized, 6-month dietary intervention DiOGenes (diet, obesity, and genes) family-based study. PATIENTS AND METHODS: In the study, 827 children (381 boys and 446 girls), aged 5 to 18 years, completed baseline examinations. Families with parents who lost ≥8% of their weight during an 8-week run-in low-calorie diet period were randomly assigned to 1 of 5 ad libitum diets: low protein (LP)/low glycemic index (LGI); LP/high GI (HGI); high protein (HP)/LGI; HP/HGI; and control diet. The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups. There were 658 children examined after 4 weeks. Advice on food-choice modification was provided at 6 visits during this period. No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation. Anthropometric measurements and body composition were assessed at baseline, week 4, and week 26. RESULTS: In the study, 465 children (58.1%) completed all assessments. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points, respectively. The LP/HGI group increased body fat percentage significantly more than the other groups (P = .040; partial η2 = 0.039), and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention (P = .031). CONCLUSIONS: Neither GI nor protein had an isolated effect on body composition. However, the LP/HGI combination increased body fat, whereas the HP/LGI combination was protective against obesity in this sample of children.

Weight loss maintenance in overweight subjects on ad libitum diets with high or low protein content and glycemic index: the DIOGENES trial 12-month results.

Background:A high dietary protein (P) content and low glycemic index (LGI) have been suggested to be beneficial for weight management, but long-term studies are scarce.Objective:The DIOGENES randomized clinical trial investigated the effect of P and GI on weight loss maintenance in overweight or obese adults in eight centers across Europe. This study reports the 1-year results in two of the centers that extended the intervention to 1 year.Method:After an 8-week low-calorie diet (LCD), 256 adults (body mass index >27 kg m−2) were randomized to five ad libitum diets for 12 months: high P/LGI (HP/LGI), HP/high GI (HP/HGI), low P/LGI (LP/LGI), LP/HGI and a control diet. During the first 6 months, foods were provided for free through a shop system and during the whole 12-month period, subjects received guidance by a dietician. Primary outcome variable was the change in body weight over the 12-month intervention period.Results:During the LCD period, subjects lost 11.2 (10.8, 12.0) kg (mean (95% confidence interval (CI))). Average weight regain over the 12-month intervention period was 3.9 (95% CI 3.0–4.8) kg. Subjects on the HP diets regained less weight than subjects on the LP diets. The difference in weight regain after 1 year was 2.0 (0.4, 3.6) kg (P=0.017) (completers analysis, N=139) or 2.8 (1.4, 4.1) kg (P<0.001) (intention-to-treat analysis, N=256). No consistent effect of GI on weight regain was found. There were no clinically relevant differences in changes in cardiometabolic risk factors among diet groups.Conclusion:A higher protein content of an ad libitum diet improves weight loss maintenance in overweight and obese adults over 12 months.

Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine

OBJECTIVE:To reveal whether baseline body mass index (BMI), and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program, including low-energy diet, increased physical activity, cognitive behavior therapy and sibutramine. The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated.DESIGN:During a double-blind placebo-controlled 4-month period, subjects received either sibutramine (10 mg/day) or placebo. Then, an open phase with sibutramine administered to all patients continued until month 12.SUBJECTS:In total, 80 obese women (age: 43.9±10.6 y, BMI: 36.7±4.8 kg/m2).MEASUREMENTS:The dependent variable was change in BMI while baseline BMI, mode of treatment, the Beck depression score, the three items (dietary restraint, disinhibition and perceived hunger) of the Eating Inventory (EI), energy and macronutrient intakes were independent variables. At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake.RESULTS:Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI, whereas a borderline negative relationship was observed with the baseline restraint score. Baseline BMI, depression score, restraint score and total energy intake predicted weight loss at month 12. These predictive variables accounted for 43.8% of the variance in BMI loss at 12 months. When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment, a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease.CONCLUSIONS:Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine.

A twin study of weight loss and metabolic efficiency

OBJECTIVE: To assess the genetic contribution to determinants of therapeutic weight loss in obese female identical twins.DESIGN: Subjects were studied for 40 days on an inpatient unit in three phases: 7 baseline days; 28 days of weight reduction by a very low calorie diet (1.6 MJ per day); and 5 days after weight reduction.SUBJECTS: Fourteen pairs of premenopausal obese female identical twins (age: 39.0±1.7 y; body weight (BW): 93.9±21.2 kg; body mass index (BMI): 34.2±7.8 kg/m2).MEASUREMENTS: Body composition by hydrodensitometry and resting metabolic rate by indirect calorimetry were assessed before and after weight loss.RESULTS: There was great variability among pairs in loss of weight (5.9–12.4 kg) and body fat (3.1–12.4 kg). By contrast, the intraclass correlation (ICC) within twin pairs was 0.85, P<0.001 for weight and 0.88, P<0.001 for body fat. A measure of metabolic efficiency, calculated as the difference between ‘estimated’ and ‘measured’ energy deficit showed high intrapair correlation (ICC=0.77; P<0.001).CONCLUSIONS: The high correlation in metabolic efficiency within twin pairs in response to therapeutic weight loss suggests a strong genetic contribution.International Journal of Obesity (2001) 25, 533–537

Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CE), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 IPR, of which 6 were essential FA including arachidonate (r=0.76, P<0.0005), eicosapentaenoate (r=0.78, P<0.0005), and docosahexaenoate (r=0.86, P<0.0001). The PC IPR could not be explained by analysis of preadmission 7-d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene-environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet.

Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: The Diogenes study

Objective:The purpose of this study was to investigate whether pre-treatment subject characteristics and weight change during the first weeks of a low-calorie diet (LCD) can predict weight loss outcomes at the end of a controlled 8-week weight loss period in overweight and obese adults.Subjects:A total of 932 overweight and obese subjects of both genders were included at eight European centers, and underwent an 8-week LCD period.Results:The weight loss at week 8 was positively correlated with initial body weight (Spearmans ρ=0.62), height (ρ=0.43), body mass index (ρ=0.43), waist (ρ=0.48) and hip circumference (ρ=0.33), sagittal diameter (ρ=0.45), fat mass (ρ=0.35) and fat-free mass (ρ=0.52), and gender (ρ=−0.36) (all P<0.01). In the multivariate regression model, adjusted for center, only initial body weight, early weight loss (week 1) and weight loss at week 3 were significant predictors of weight loss outcome at week 8: weight loss (kg) at week 8=0.09+0.046 × baseline body weight (kg)−0.311 × weight loss (kg) at week 1+1.284 × weight loss (kg) at week 3 (R 2=68%, P<0.0001). A weight loss of ⩾2.6 kg at week 1 during the LCD period was identified as the optimal cut-off predictor for at least 10 kg weight loss at week 8.Conclusions:This study suggests that initial body weight, early weight loss (week 1) and weight loss at week 3 are predictors of final weight loss during an 8-week LCD, and may be used as early biomarkers of subsequent responses to an LCD diet.

The Eating Inventory, body adiposity and prevalence of diseases in a quota sample of Czech adults.

Objective:To study the relationships between the Eating Inventory (EI) factors (restraint, disinhibition and hunger), body adiposity and prevalence of selected diseases in a quota sample of Czech adults.Subjects and methods:The sample included 1429 men and 1624 women who were interviewed individually by trained investigators. The sample was quota representative – for gender, age, size of residential location, region and socioeconomic status in Czech adults. Anthropometric data, socioeconomic and lifestyle information were obtained. Subjects filled out the EI questionnaire. Physicians reported about subjects’ morbidity.Results:Backward stepwise regression analysis revealed that restraint and disinhibition were significant predictors of body mass index (BMI) along with gender, age, parental obesity, weight loss attempts, present dieting and educational level. The same factors plus income predicted the waist circumference. BMI and waist circumference were negatively related to restraint but positively to disinhibition. According to logistic regression analysis restraint and disinhibition were significantly associated with hypertension, cardiovascular diseases and hyperlipidaemia. Diabetes was significantly related to restraint and hunger scores. The observed association between EI factors and diseases remained significant even when BMI and age were taken into account.Conclusion:As shown in earlier studies, disinhibition was positively and restraint negatively associated with BMI and waist circumference. For the first time, factors of the EI were also identified as significant predictors of diseases characterizing the metabolic syndrome.