Chris Adriaanse talks to Dr Rosemary Hall about her research on human nutrition and risks of obesity and diabetes

Tell me a bit about the MRC HNR.

The MRC HNR is one of 40 MRC units throughout the country. Our unit was formed just under 10 years ago when the MRC Dunn Nutrition Research unit, based at Addenbrooke's Hospital, was restructured. Our role is to advance the knowledge of the relationships between human nutrition and health.

What research does the HNR conduct?

We carry out research into the relationships between nutrition and health that are considered a national or international priority, and work with governments, industry and academic groups. The unit is involved in translating the research we do into important public health and nutrition messages for the population, by acting as an independent source of advice and information. In practice this means a number of different research groups working towards the common goal of determining how nutrition affects various aspects of health.

What is your group's focus?

My group, led by Dr Susan Jebb, is called Nutrition and Health Research and we are looking at the link between obesity and metabolic diseases. We're interested in why some people become overweight-what causes it? How does it occur? And then, more importantly, why do some overweight people develop metabolic and cardiovascular diseases? We look at what is termed the 'metabolic syndrome': a cluster of factors that predict your risk of developing these diseases. Those at high risk typically have a large waist circumference, high blood-glucose levels, high cholesterol and high blood pressure. The rate of obesity in the UK, and in fact worldwide, has increased dramatically over the last 50 years and the public health burden is really significant. It is important to work out how we can reduce it, and particularly how we can reduce the number of people who develop diabetes and heart disease as a result of their excess body fat. We're trying to find out which factors predispose people to being overweight, with the aim of being able to alter their metabolic risk by altering their diet.

How did you become involved in nutrition research? Why did you specialise in this particular area?

I am a specialist physician in diabetes and endocrinology, the medicine of metabolic diseases and hormone-related diseases. This is an interesting area for a number of different reasons. One of these is that it is preventative medicine-treating people with diabetes is treating essentially healthy people (with established risks for future problems) in order to prevent them from becoming unwell. There is fascinating medicine and physiology involved, and it's a growing area-which is obviously not a great thing-so it's important to have people who can provide treatment.

I worked as a physician in New Zealand before coming to Cambridge. What brought me to the MRC HNR was the desire to do some research outside of New Zealand and gain a thorough understanding of nutrition in order to help my patients. In the majority of the patients I saw, an important factor in their disease management was improving their lifestyle risk factors, particularly diet and exercise.

What can you tell me about your current research interests?

I am looking at how particular aspects of diet impact upon energy regulation. If we're not gaining or losing weight we are in energy balance. What goes in equals what goes out; energy from food is equal to our energy expenditure from physical activity, expenditure at rest and our basal metabolic rate. I am doing experimental work to see whether particular types of food have any impact on this balance and also whether they affect body composition: the ratio of fat to lean tissue to bone.

It is not just weight as such that puts you at risk of metabolic diseases, but whether your weight is made up of lean or fat tissue. Stored fat is one of the biggest producers of hormones-previously we thought fat was inert and just sat there as a storage depot. In fact, it produces a lot of different hormones, many of which we don't really know much about. And if you reduce the fat, particularly central (or abdominal) fat, it appears that you change the ratio of circulating hormones. These can interact with your hypothalamus (the centre in your brain that controls appetite) to regulate your body weight. Reducing weight, particularly abdominal fat can reduce your metabolic risk and risk of developing diabetes and heart disease.

You need volunteers for research. How does that work?

In my current project we have volunteers who come to the MRC HNR for a week at a time on three different occasions to allow us to look at the effects of diet on energy balance. Being able to compare the same person over time makes for a much more meaningful study. During the week we provide all of the food they eat and measure energy expenditure; both metabolic rate and body composition are measured, culminating in time spent in a room calorimeter where we can very carefully calculate energy expenditure under controlled conditions. If you can change the type of food that people eat to help increase their energy expenditure this could help to either maintain their weight or prevent weight gain by adjusting the energy balance equation. If we can establish whether different macronutrients can alter energy balance following a meal, we can advise people on an appropriate diet to help maintain their body weight.

The other component is the important process of glucose metabolism, which, when it goes wrong, leads to diabetes and a major risk of heart disease. If we can affect the way we metabolise glucose, particularly after a meal, then that can reduce the risk of metabolic disease. When you eat a meal your glucose value rises quite substantially and then falls back to your baseline. This pattern changes quite significantly for different amounts and types of food. Your risk of metabolic diseases is increased by longer and higher excursions from the baseline glucose levels. If we can alter the ratio of macronutrients to even out the post-meal glucose levels we can reduce this risk, or help people to manage their diabetes.

It must take quite a lot of work to prepare the food.

It does take quite a bit of time. We have a research kitchen with all the facilities to prepare and cook the food. All of the food has been carefully calculated so we know exactly what goes into everything we make. The way it is cooked is standardised, the way it is stored is standardised and the way it is heated is standardised. It's just like being in a lab but these carefully controlled conditions mean that we can really pinpoint any existing differences.

You hold certain information back from volunteers about the aims of the study. Why is this?

We are trying to measure particular factors that would be altered if people knew they were being measured. We are trying to find out how our physiology, rather than the brain, controls what we do. If we tell people exactly what is going on all the time then their brain may override their natural response. For example if we told participants that we were looking at fruit and vegetable intake they may alter their usual intake of these foods because they know it is the focus of the study, rather than behaving naturally. It's the same with any drug trial. You don't tell people what drug they are taking to avoid the placebo effect. However the study is explained in detail to participants when it has been completed.

How does your week unfold?

Before the volunteers come for the week we ensure we have all the food and equipment prepared, making sure everything is carefully labelled and everyone knows what is happening. When volunteers come it is really a matter of making sure they are comfortable in the volunteer suite and then continuing with food preparation and provision. When the volunteers are not around we upload all the collected information onto the database. Much of the analysis, including blood test and data analysis, will be done later when this year's group of volunteers is finished.

Feeding experiments were popular over 100 years ago. What can technology bring and why repeat them?

In order to be sure that what you found the first time is actually correct, it is always necessary to repeat experiments. That said, at the MRC HNR we are obviously trying to do something new as well. One of the major factors that has changed in the past 100 years is the realisation of the importance of having enough people in a study. We will be looking at about 20 people over two years, and because they come for three visits each this increases the statistical power and accuracy of the study.

There is an enormous amount of new information on metabolites and hormones and the ease with which we can analyse them just wasn't there in the past. At Addenbrooke's Hospital we have some very sophisticated room calorimeters. They allow us to measure energy expenditure very accurately-we can break it down into how much energy is used sleeping, after meals, at rest or exercising.

What have you learnt from your own research? Any take-home messages?

My research and my involvement in the Nutrition and Health Research group has emphasised to me the importance of a good diet in maintaining good health and reducing future risk of disease. It is important for everyone to know what they are eating and to enjoy nutritious food in an appropriate quantity.

www.mrc-hnr.cam.ac.uk

Chris Adriaanse is a PhD student in the Department of Chemistry