Fredrik Karpe: Obesity and Diabetes

Q: How does obesity influence diabetes?

FK: At several levels, and obesity is actually the single most important factor for the increase in diabetes we see right now. We all know that people are becoming fatter and fatter, that is something we can see. The way it works is not entirely clear, but we know that obesity increases the demand for insulin secretion, and where the demand is not met, the pancreas doesn't secret enough insulin, there isn't enough insulin around to lower the glucose, and we actually get diabetes.

Q: Are there different types of obesity?

FK: Yes, I think the focus has been very much on abdominal obesity, the male pattern type of obesity, because it is so strongly associated with diabetes and heart disease and a variety of other illnesses as well. It is interesting to note however that there is a female pattern of obesity, that is the lower body fat, and that has the opposite associations; you are actually protected as a woman with big hips. Women don't like to hear that but it is actually the case! The most extreme variant is when adipose tissue doesn't work any longer, and you lose the fat completely, or in parts of the body, and then you get into real trouble metabolically.

Q: I thought that fat was just stored, how can they be so different?

FK: I think that is something we are learning more and more about. It is probably down to the architecture and the origin of the actual fat cells. They seem, when we look at them closely, to be coming from different types of stem cells and have markers with that. I think that in that we have some of the origins of the rather troublesome and difficult conditions that I talked about, the lipodystrophy, when you lose fat. We have actually recently studied one particular patient who underwent surgery, bariatric surgery for obesity, and she lost a phenomenal amount of fat. Her diabetes disappeared after only a couple of weeks. It was a bit of a miracle, and we have actually never done that in such a patient before so that is actually new for Oxford.

Q: What are the most important lines of research that have developed over the last five or ten years?

FK: In this particular area (obesity and the links to diabetes), I think it has become clear over the past years that obesity as such emerges from energy balance that is driven by satiety, and that is governed by central systems; recognition in the brain etc. Whereas the complications of obesity and this is new, arises from things going wrong in the periphery; in the skeletal muscle, adipose tissue, and also the liver.

Q: Why does your line of research matter? Why should we put money into it?

FK: I think it is almost self evident when more than 10% of the entire NHS budget goes to obesity and diabetes and its complications, and it might not be enough to count only 10% because obesity is related to so many other things which cost society a lot of money such as depression, cancer, and other major disease areas.

Q: How does your research fit into translational medicine within the department?

FK: We have benefited a lot from one of Oxford's real strengths, and that's the elucidation of some of the genes underlying complex disorders such as diabetes and obesity. Now is the time to harvest and translate this into the benefit of patients. We are actually funded by the Oxford Biomedical Research Centre to do research along that line. It is not trivial; it is not an easy step to go from molecule to patient. It needs several steps and one of the steps that I believe is quite important is to have a link between the molecule and the patient to understand physiology and function. For that reason we have set up something called the Oxford Biobank where we can go into the population and ask people with certain genetic variants, or certain characteristics to come back and take part in research and help us to understand function before we move into studying patients and liaise with external companies or our own research lines to find new therapies for diabetes and obesity.