Dr Roy Taylor is a world-renowned researcher who pioneered studies on the possibility of diabetes remission. On his recent visit to Kerala, Taylor spoke to THE WEEK about his research and his famous twin-cycle hypothesis. Excerpts from an exclusive interview:
How did you arrive at the twin-cycle hypothesis?
The basis of the hypothesis was the work that I had done to try and understand how the body and, in particular, how the liver was controlling the glucose level. I found that the fat in the liver makes it resistant to insulin and glucose production is far too high in type 2 diabetes [patients]. If we reduce the amount of fat in the liver, the insulin sensitivity goes back to normal. That explains the control of sugar in type 2 diabetes. So, this was 2008. And, I put that together with another thought which was if it is too much fat in the liver that is causing this, type 2 diabetes has to be a simple condition. It is always associated with putting on a little bit more weight than ideal. So, I put together my thoughts on the liver with what is happening where the insulin was produced, which is the pancreas. And I said, ‘What if it is too much fat in the pancreas that is causing the problem of not making enough insulin?’Because not only does the insulin not work because of insulin resistance but also not enough insulin is being made rapidly after eating. As I played with these ideas on a piece of paper and drew arrows between the things, I could see it all work as two vicious cycles.
One vicious cycle in the liver would cause a steady buildup of fat in the liver, but then that fat is going to be exported. That is what the liver does. It just gives fat to the rest of the body. If it is too much fat in the liver, maybe too much fat is coming out of it as well and settling in the pancreas and other places. And then that would cause blood sugar to go higher, and that will make more fat in the liver. So we have two vicious cycles, which are interacting.
So that was the twin-cycle hypothesis and it carried the vital prediction that if we reduce the amount of fat in the organs, everything should go back to normal. Now that seemed unbelievable because everybody used to think that type 2 diabetes [cannot be reversed], but I was looking at a hypothesis that says it could be reversed. So, I decided to test this and that's where our counterpoint study came in. I had to invent a diet or a way of losing weight very rapidly. I wanted people to lose 15kg in eight weeks. I chose that target partly because the research money was for a short period of just two years and to be able to study all the patients we needed to have a sure-fire way of losing weight that would work over a short period. But there was an ulterior motive. I know from talking to my patients over many decades that it is much easier to do things for a short while―so focus on weight loss. In eight weeks, the average weight loss observed was 15.3kg. So, it was enormously successful in doing what we needed to do to test the hypothesis. So, we have produced the right conditions. To my astonishment, the blood sugar came down to normal after seven days. They were a mixture of people with a body mass index of 27 up to 45.
But it is not only blood sugar that we measured. I developed a magnetic resonance research centre to help my research on the liver. And, using it we started investigating what happened when the level of fat inside the liver went down. When the fat in the liver went down rapidly, gradually the level of fat in the pancreas went down. People with diabetes had higher than normal levels and this is the first time it was shown that it came down with weight loss. And the insulin-producing cells in the pancreas woke up. So, this was revolutionary stuff and it was so dramatic that doctors were very slow to believe it.
Could you please tell me about your further studies and the publishing of the famous DiRECT study?
After 2011, when we published the counterpoint study―as it was called―we needed answers to two questions. The first: is this something that can be achieved in everyone with type 2 diabetes? Because to test the hypothesis, I studied people only in the first four years after diagnosis. So in counterbalance, we studied people of any duration and what we found was very striking. In the first 10 years, there was a very good chance of reversing diabetes, but it did go down even in those first 10 years and after 10 years the chance of reversing it was much less. So we then knew the diagnosis had to be fairly early and that's why in the DiRECT study, I made the arbitrary decision: six years would be a nice compromise to have most people who could reverse their diabetes; some would not be able to, but most people could.
But the second thing about this counterbalance study was we wanted to follow up. Because a lot of the experts said ‘Look you've just starved people. Of course, diabetes went away. But it's going to come right back as soon as people go back to normal eating.’I did not think that was true. So, we did this counterbalance study where we dropped people's weight by a similar amount and then just asked them to keep their weight steady and we achieved that over six months. The improvements remained; the level of fat inside the liver stayed normal. The insulin production from the pancreas went back to normal. So, it was the counterbalance that set the scene for the big DiRECT study because here we see this could be clinically useful.
Now, most people with type 2 diabetes are managed in primary care. So we had to run a study in primary care; it had to be quite a large study. We studied just under 300 people divided equally between people who have the best possible treatment and people who have undergone weight loss treatment and we found that at 12 months, almost half of the people in weight loss treatment had no diabetes. They stopped their tablets; the sugar level was normal.
Naysayers were still saying this won't last and people will grow heavier than they used to be. It didn't happen so. In two years, people had let their weight creep up a little bit. But even so over a third had no diabetes. Now, we are analysing the five-year followup of the DiRECT study and I don't yet have the final data of that but I know from individuals that if people lose weight and keep the weight off, type 2 diabetes does not come back.
How challenging is it to prevent weight gain and sustain the effects of weight loss?
Losing weight is comparatively easy compared with preventing weight gain because when we humans go back to the same food environment that we had before, eating with a family, eating with our friends and meeting socially, it is very difficult to just backpedal and keep the weight down. There's a real human problem, but it's not a biological problem and we need to distinguish between these two things. If people are successful in keeping their weight down, diabetes stays away. But if the weight goes back to what it was, there's 100 per cent certainty that diabetes will come back.