Physical activity for a long and healthy life (FINE)

Overweight and obesity - an epidemic?

The increase in the prevalence of overweight and obesity among all age groups in the Western world is so dramatic that the World Health Organisation (WHO) has classified it as an epidemic. Overweight is caused by a positive energy balance, which is partially due to a modern lifestyle that involves using forms of transportation that do not require physical exertion, working at sedentary jobs, and having a lack of physically active leisure pursuits in addition to regularly over-consuming food.

Overweight and lifestyle diseases

Overweight and obese individuals have a much higher risk of developing lifestyle diseases such as type 2 diabetes and cardiovascular disease, but the risk varies from person to person and cannot be explained only by differences in lifestyle factors. Thus, both genetic and epigenetic factors appear to regulate insulin sensitivity as well as beta cell function, and these conditions seem to determine an individual's likelihood for developing conditions later in life that are related to being overweight, such as diabetes and cardiovascular disease.

Physical activity is the key to a long and healthy life

Due to the rapidly increasing prevalence of overweight and obesity in modern society, there is now a growing focus on the fact that physical activity is a cornerstone of successful weight management. Health authorities in Denmark and a number of other countries recommend at least 30 minutes of daily physical activity, in order to prevent lifestyle diseases related to being overweight, and to add "years to life" as well as "life to years". However, at least 60 minutes of physical activity every day is recommended for overweight individuals who want to lose weight.

Objective

This study investigates overweight and physical exercise from the perspective of health promotion, and uses medical, scientific and humanities research methods. In our opinion, this variety of approaches is particularly relevant and innovative. Central to this study is the concept of health, which is defined by the WHO as "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity."

Hypotheses

The molecular mechanisms behind the large variation of insulin sensitivity within the population may essentially be attributed to differences in the molecular and structural conditions of skeletal musculature. This is investigated in subproject 1.

The dose-response effects of physical exercise vary among different metabolic health parameters. Parameters related to the metabolism of skeletal musculature show a maximum response even with moderate doses of physical exercise, whereas parameters related to the metabolism of fatty tissue and the liver require high doses of physical exercise to achieve a maximum response. This is investigated in subproject 2.

Twelve weeks of high-dose physical exercise do not significantly affect the caloric intake of overweight men, which results in a negative energy balance in relation to the energy burned during exercise and thus weight loss. The energy use during 12 weeks of moderate-dose physical exercise is not great enough to significantly affect energy balance. This is investigated in subproject 3.

Identifying the social and cultural barriers to a change in behaviour and practice - as well as the health-promotion initiatives that have a positive effect - could contribute to the production of better strategies that encourage changes in health behaviour. This is investigated in subproject 4.

Criteria

All the people who participated in the project met the following criteria:

• Men between 20 and 40 years of age.
• Moderately overweight, BMI = 25-30 kg/m2. Body Mass Index = weight (in kg) divided by height squared (m2). 
• Healthy and not regularly taking any medications.
• No type 2 diabetes in their immediate families (parents and siblings). 
• Do not exercise regularly. 
• Caucasian (other ethnicities may increase data variation). 
• Do not suffer from anaemia: haemoglobin concentration ≥ 8.0 mmol/L.

The three test groups

After drawing lots, the participants in the exercise study were divided into 3 groups:

Group 1 - High-dose physical exercise
Participants in this group exercised 7 days a week with a calorie consumption of 600 kcal per exercise session. This was equivalent to approximately 1 hour per day. From previous studies, our experience was that this is a realistic goal. The participants were not asked to change their habits in any other way.

Group 2 - Moderate-dose physical exercise
Participants in this group exercised 7 days a week with a calorie consumption of 300 kcal per exercise session. This was equivalent to approximately ½ hour per day. The participants were not asked to change their habits in any other way.

Group 3 - Control group
Participants in this group continued to live as usual. That is, they did not change their exercise or dietary habits at all. After the test period, they were offered advice on exercise and diet, and a follow-up fitness test, if they wished.

Test period

The test period was approximately 15 weeks, and the exercise intervention period lasted 12 weeks. During the test period, the diet and activity levels of the participants were periodically registered. They also had to meet regularly at the Faculty of Health Sciences, the Panum Institute.

Before and after the test period, there was 1 long day of tests at Copenhagen University Hospital, and 4 shorter test days at the University of Copenhagen's Department of Human Nutrition (Frederiksberg), the Panum Institute and Glostrup Hospital.

Test schedule

Test day 1 at the Panum Institute (approx. 4 hours): The participants fasted prior to their arrival. Their body composition was measured using DXA (dual-emission X-ray absorptiometry) scans, and their sugar metabolism was measured after they drank 75g of a sugar solution. Their fitness levels were also measured using a cycling test.

Test day 2 at the Panum Institute (approx. 3 hours): The participants fasted prior to their arrival. They cycled for 1 hour at 60% of their maximum performance level, and then rested for 1 hour.

Test day 3 at Copenhagen University Hospital (approx. 10 hours): The participants fasted prior to their arrival. Their sugar metabolism was measured, and they each had two muscle and fat biopsies taken. After this, the sugar metabolism of their muscles was measured using a low-dose PET-CT scan.

Test day 4 at the Department of Human Nutrition (approx. 4 hours): The participants fasted prior to their arrival, but were served a morning meal and a lunchtime meal. After this, they were provided with all of their food for the next 8 days.

Test day 5 at Glostrup Hospital (approx. 2 hours): The participants fasted prior to their arrival in the afternoon, and the amount of fat in their stomachs and thighs was determined using magnetic resonance imaging (MRI) scans.

The tests also included taking blood and tissue samples. At the end of the test period, the participants each received DKK 7.000 in remuneration for their involvement in the project.

Subproject 1: The variation of insulin sensitivity in the population

In the population as a whole, the effectiveness of the hormone insulin varies greatly. The objective of this part of the project was to identify the molecular mechanisms underlying the variation in insulin sensitivity. The consequence of a variation in insulin sensitivity is that the most insulin-resistant individuals have a concentration of insulin in their blood throughout the day that is 2 to 3 times higher than the most sensitive individuals, leading to the development of dyslipidaemia. This results in an increased incidence of arteriosclerosis and type 2 diabetes. The skeletal musculature is mainly responsible for dispersing carbohydrates after a meal; therefore, it is primarily in this tissue that the pathophysiological mechanisms of insulin resistance are expected to be identified.

Subproject 2: Dose-response effects of physical exercise

Physical exercise exerts dose-response effects, and in general, ‘the more, the better' applies. However, dose-response effects vary between different metabolic risk parameters (e.g., cholesterol levels, insulin resistance). Therefore, the maximum beneficial effect for a given parameter is not necessarily achieved at the same dose of physical activity as for a different parameter.

The objective of this part of the project was to identify and describe in more detail the mechanisms underlying the dose-response effects of physical exercise on metabolic health parameters, using both integrative and molecular techniques as well as self-evaluations of health.

Subproject 3: Physical exercise and energy balance

It is widely believed that physical exercise is not an effective method to induce weight loss because physical exercise stimulates caloric intake. However, very few human studies have investigated the long-term effects of physical exercise on caloric intake.

Therefore, the objective of this part of the project was to investigate how physical exercise influences the overweight men's caloric intake, body weight and appetite-regulating hormones as well as the composition of their diets and dietary choices.

Subproject 4: Cultural barriers to physical exercise

This part of the project used qualitative methods to focus on the test participants' motivations, experiences and potential barriers in relation to physical exercise.

The main objective was to identify the social and cultural ideas, expectations, and experiences related to the effects of exercise. An additional objective was to contribute social and cultural insights in order to qualify what it means to add not only ‘years to life' but also ‘life to years'. Furthermore, this subproject focused on the long-term effects of physical exercise on health and the quality of life as well as on how a user-perspective can be included in health promotion efforts in general.

Project FINE is a collaboration between a number of faculties and hospitals. The objective is to:

The FINE team and its collaborative partners aim at preventing and treating lifestyle diseases.

Faculty of Health Sciences (SUND)
Department of Biomedical Sciences: Professor Jens Juul Holst, professor Thomas Mandrup-Poulsen, professor Klaus Qvortrup.

SCIENCE
Department of Human Nutrition: Professor Lars Ove Dragsted. 
Department of Food Science, Quality & Technology: Professor Søren Balling Engelsen

Faculty of Humanities
Saxo Institute: Associate Professor Astrid Pernille Jespersen.

Faculty of Pharmaceutical Sciences
Department of Pharmacology and Pharmacotherapy: Professor Harald S. Hansen. 

Rigshospitalet
Metabolic Mass-Spectrometry Facility: Senior researcher Gerrit van Hall. 
Department of Clinical Physiology, Nuclear Medicine & PET: Professor Liselotte Højgaard, Professor Andreas Kjær, Head physicist Søren Holm.

Glostrup Hospital
 Functional Imaging Unit: Professor Henrik Larsson, Chief physician Egill Rostrup, Physicist Adam Espe Hansen