I come from Finland, and that’s where I completed high school. For a long time I’d wanted to work as a doctor, and I was fortunate to get admittance to medical school in Bern, Switzerland. Then for my PhD I stayed in Switzerland, and when I had completed that I went back to Helsinki, where I worked on a second doctoral thesis for my M.D. This was on diabetes, which has formed the basis of my research ever since. Actually, as a doctoral student I found the work quite boring, and I didn’t initially get into diabetes research with a really passionate ambition to work on that particular condition!

  How was your early research career developed?

The person who introduced me to medical science was a neurologist in Bern, so I did a small amount of research initially in neurology and wrote a short dissertation. But the reason I switched to diabetes was because one of the first research positions brought me into contact with a consultant who unfortunately had a very cynical attitude towards diabetic patients. I was upset by his attitude, and just felt I wanted to show him his attitude was wrong. So I suppose I am an example of a person going into a scientific area because of a personal challenge that I wanted to overcome.

My postdoctoral training was at Yale University (1984-86), which attracted me because at that time it was probably one of the best centers in the world for diabetes research. For example, in terms of the effects of diabetes on metabolism, a lot of the people who were at Yale in my time are now world-famous diabetologists today, although at the time I wasn’t aware of the high level of excellence in the department!

After two years at Yale I returned to Finland for some years, and then in 1993 I moved to Sweden. So today I am working at Lund University, Malmö, in the Wallenberg Laboratory and the Department of Endocrinology.

  What’s been the intellectual driver of your research program for the past decade or so?

Diabetes mellitus is increasing worldwide, and it’s probably the disease with the most rapid rate of increase right now: it’s even more rapid than AIDS. There are two main types of the disease. The more severe form, type 1, is insulin-dependent. Type 2, or non-insulin-dependent diabetes, is commoner. Basically we’ve set up a research program that can be described in very simple terms: what causes diabetes and why is its growth exploding?

To get to the bottom of this we’re using all the available tools, particularly genetics, metabolism, and cell biology with the aim of getting knowledge that will enable us to find a treatment.

The need for effective treatments is underscored by the fact that, worldwide, 150 million people have diabetes, but really the tragedy is that 10 years from now we estimate that it will afflict 220 million, a 50% increase. Diabetes mellitus is not an innocent condition. Most people in the developing countries in Africa, Asia, and China are getting this disease from the age of 30 and they die from the complications between the ages of 40 and 50. This is a really severe problem.

In the earlier part of my career I had success with a paper which described the basic defects in pre-diabetic individuals. (J. Eriksson, A. Franssila-Kallunki, A. Ekstrand, C. Saloranta, E. Widen, C. Schalin, L. Groop, "Early metabolic defects in persons at increased risk for non-insulin dependent diabetes mellitus," New England Journal of Medicine, 321 [6]: 337-43, 1989). What we did was assemble the available tools to get good estimates of insulin secretion, insulin action, and also glucose produced in the liver. Good luck was involved: the right idea and having the right tools to follow it up. When I was in the USA we had a lot of technical difficulties with equipment, to the point where engineers were making weekly calls to keep us going. Back in Finland I found that young engineers had solved all the technical problems that plagued us. We had good instrumentation to monitor energy consumption, and to see how much comes from sugar, how much from fat, and how much from protein. I could hardly believe it: suddenly I had access to the best equipment in the world for monitoring metabolism in the diabetic patient. Now everybody is using what we, as world leaders, pioneered.

  In your papers since 1990, the most-cited is about the effect of a drug captopril, on patients with type 1 diabetes. (G. Viberti et al., "Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria," Journal of the American Medical Association, 271 [4]: 275-279, 1994). Why has this created so much interest?

This is not one of my favorites, and I did not give the lead. It was a straightforward randomized double-blind trial of the drug, and we used 12 diabetes centers. We found that the drug has a significant effect of slowing progression to a kidney disease associated with type 1 diabetes. The work is very important, but the paper touched on a very commercialized field, and I think the high citation level is due to citations from within the pharmaceutical industry, in conference proceedings and supplements to journals.

  Your next most-cited paper from this period is about the classification of adults with diabetes. (T. Tuomi et al., Antibodies to glutamic-acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease," Diabetes, 42 [2]: 359-362, 1993). What particular contribution did this make?

We defined a new subgroup of diabetes, which was major news at the time. The subgroup consists of people who start out with type 2, the milder condition, but who then progress to type 1. About 10% of patients fall into this group, which is comparable to the numbers presenting with type 1. So this latent subgroup is just as important as the type 1 group. This paper is actually a follow-up to research published in 1986. But in the 1993 paper we really get to grips with defining this diabetic subgroup, which is now widely accepted. The measurement of antibodies to glutamic-acid decarboxylase provides a means for the correct classification, and opens up the possibility for earlier intervention.

  I’m very interested in the third paper we’ve picked, because this one illustrates the extraordinary diversity of your research. This is where you make a decisive move into the genetics of diabetes. (L. C. Groop, et al., "Association between polymorphism of the glycogen-synthase gene and non-insulin-dependent diabetes mellitus," New England Journal of Medicine, 328 [1]: 10-4, 1993).

This is the area we’re working on today in fact. The paper is a follow-up to our earlier 1989 paper, but this time we’re looking at the genetics of why the storage of glucose as glycogen in skeletal muscle is impaired in patients with type 2 diabetes. The reason for the high level of interest in this study is that we had a very good patient population and first-rate analytic techniques. It was a question of bringing everything together at the right time. We found a genotype that is present in 30% of patients with a family history of type 2, whereas the genotype appeared in only 8% of patients with no family history of the disease. Our discovery set the scene for genetic investigations.

In a nutshell, we’re continuing with the lines of research suggested by the above papers. We are really trying to dissect the genetic element in diabetes, and explain the heterogeneity of the disease. This disease is a collision between genetics and the natural environment, the food we eat. I am trying to identify the genes that in another environment could well be protective because they help us to store energy very efficiently, but in our environment they are threatening. I want to know what these genes are and what they mean.

The classification into type 1 and type 2 is too simple. What I’m now trying to do is to create a pie chart covering the spectrum of the disease. This is part of finding all the causes, and putting the data into the melting pot to see what’s really going on.

When I’m not fishing genes I’m fishing fish from my summer house in the Gulf of Botnia.

Coincidentally, this is where we have the Botnia Study, which has been running 10 years. We have 1,400 families with type 2 diabetes which we assess every three years. Our major task is performing a genome-wide search of these families. There is frequently type 1 and 2 in the same families, so another target of our research is to explore whether a genetic interaction exists between type 1 and type 2 diabetes. The strength of this research group is the access to unique family material from isolated populations and the close connection between physiology, metabolism, and molecular biology. This is the largest study in the world for type 2 diabetes.

Professor Leif Groop, M.D., Ph.D.
Lund University
University Hospital Malmö
Malmö, Sweden