Monday, June 10, 2013

Diet, obesity and genes

The World Health Organization projects that by 2015, approximately 700 million adults will be obese. The Diogenes Project is one of the largest projects worldwide targeting the obesity problem from a dietary perspective.
Diogenes, an acronym for “Diet, Obesity and Genes” is one of the largest projects worldwide targeting the obesity problem from a dietary perspective. The Diogenes Team, with Professor Wim Saris from the University of Maastricht as its Executive Director, has performed multi-disciplinary, multi-center international research by integrating studies of dietary, genetic, physiological, psychological and food technological factors.
This project has a total budget of €21 million, including €14.5 million of European Union funding, and includes 32 partners across Europe — both (academic) research institutes and private companies. Final results will be available later this year.
Saris proudly reports on the successful integration of disciplines in the Diogenes Project. All research lines, from basic genetics up to food application, were connected to a large dietary intervention study in 8 countries, which included whole families with overweight, obese, and normal weight members. A central data hub facilitated standardization of protocols and data collection, storage of (and access to) collected research data, and the rapid and detailed analysis of the results. Furthermore, a bio bank containing, for example, plasma, adipose tissue and isolated DNA, was established.

Pan-European weight loss study

A healthcare worker assesses a child’s health.
The primary focus of Diogenes was an investigation into the role of the Glycemic Index (GI) of carbohydrates and the role of high protein content in relation to satiety enhancement. “We considered the role of fat in relation to weight to be sufficiently known,” Saris explains.
In foods with a reduced amount of fat, carbohydrate and/or protein levels will be elevated. Literature reveals that both GI and protein could be promising dietary factors for weight control with potential for the food industry.
“Literature, however, is conflicting with respect to GI effects,” Saris adds. “Therefore, for the first time, we conducted an intervention trial with respect to the effectiveness of GI and protein in prevention of weight (re)gain in an ad libitum setting.”

Long-term

The Diogenes Team managed a large, long-term, randomized, parallel dietary intervention study in eight geographic centers, in which 763 participating adults were successfully enrolled after losing more than 8% of their weight during an eightweek low-calorie diet.
After the weight loss phase of the selected adults, 565 families (763 adults and 787 children) were enrolled in the intervention study and randomly distributed into five study groups — each following different diets, either high or low in protein and/or high or low in GI carbohydrates. The fifth diet, the control diet, was based on national guidelines for a healthy diet. Special attention was paid to minimizing the burden for the children and to the potential risks associated with a high protein diet for children, in particular, with respect to growth and metabolism.

Families

In two centers (Maastricht and Copenhagen), supermarkets set up for the study provided whole families with free food for the first six months. In the subsequent six months, the same subjects only received dietary advice and support. The other six centers provided families with six months of dietary advice and support only.
The supermarket dietary intervention had been validated to allow a strict compliance to a targeted diet composition with a concomitant allowance of variable energy intake. All food items in the supermarkets were commercially available and barcoded. A dietician scanned the barcodes of all the chosen items in order to monitor macronutrient composition of the diet and assisted in altering the selection to meet the prescribed diet composition.
The calculated energy content of the chosen groceries was not made known to the subjects. Outcome measures like weight (regain) and (changes in) BMI, waist circumference, waist/hip circumference ratio, body fat (%), risk factors of type 2 diabetes and cardiovascular disease and satiety factors were determined. Physical activity was registered.

High protein content favorable

Although complete analysis of the results is still pending, interesting results already have been obtained from the two well-controlled supermarket centers.

Saris states, “Our study clearly indicates that an increased dietary protein content significantly affects weight regain in adults after a period of weight loss in a positive manner, whereas GI had no effect in these two centers. However, we have to be cautious since the number of participants is relatively low and certainly not sufficient to draw a final conclusion.”
Saris goes on to explain, “As could be expected, the positive effect of protein content on weight regain turned out to be somewhat more variable in the less-controlled setting than in the strictly controlled supermarket settings in Maastricht and Copenhagen.”
Saris continues: “We are now analyzing all other gathered data. For example, results on the (change in) weight of more than 700 children included in the trial, will become available soon.”
Researchers are studying the role genetics plays in a person’s weight.
In addition, the intervention study has been coupled to the analysis of genetic variation in candidate genes. Furthermore, characterization of biomarkers, for example, by measurement(s) of gene expression in adipose tissue and peptidomics in plasma — both types of samples having been obtained during the intervention trial — has been performed. In combination with the genetic data that the Diogenes Team is drawing from pre-existing cohorts, the Diogenes Project will significantly contribute in predicting an individual’s response to nutrients in terms of weight change, which, in turn, will guide a diet-based treatment.

Nutritional factors

The Diogenes Project could not only benefit from two twin cohorts in Finland and Denmark, but also from the large EPIC cohorts in five EU countries with a total of 145,000 subjects,for example, by comparing gene polymorphisms from 6,000 selected humans whose weight remained stable with those of 6,000 selected subjects out of the total number of subjects that gained more than 10 kg in 7 to 8 years’ time. “Understanding the genetic elements in weight management has been limited up to now,” Saris explains. “We know that energy efficiency may differ by as much as a factor of 3 between individuals. Individual susceptibility is determined largely by genetics. In this obesogenic environment, knowledge of the interactions of gene function, nutritional status, and the role of nutritional factors will be crucial in offering more individual, better matching diet-based treatments.”

Toward individual approaches

It is clear that in choosing dietary approaches with respect to weight management, other factors, like physical activity, psychological factors and behavior patterns can also influence an individual’s success in controlling weight. “A series of these kinds of predictors has been validated in the intervention study as well. For example, measurement of free living energy expenditure by the double-labelled water technique has been performed. These predictors have been integrated with the biomarker data and the actual responses to diet composition in the intervention trial. A new Obesity Risk and Behavior Advice Screening Tool (ORBAST) will be developed based on all these results. This software-based tool will assist consumers in devising, and health professionals in prescribing, individual approaches with respect to weight control,” Saris concludes.
For announcements, please check the Diogenes website: www.diogenes-eu.org.
This post is a reprint of an article that appeared in Food for Thought, a newsletter from the Netherlands Foreign Investment Agency that reports on agrofood activities and advances within the Netherlands.

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