Author: Dr. Sean Wheatley, PhD – Science and Research Lead/9th August
The DiRECT study, as well as other research, has shown us that type 2 diabetes can be put into remission. The latest paper from this study has helped shine a little bit more light on why; and on what the difference is between responders (those who achieve remission) compared to the non-responders (those who don’t). Although we don’t currently have an easy way of telling who will be a responder or a non-responder before trying an intervention, this information could have important implications and might lead to a situation where our usual “one size doesn’t fit all” message breaks down.
What is diabetes remission? A brief recap
I’ve covered this before in a little more detail, but essentially it is when someone who has type 2 diabetes is able to return to having “normal” blood glucose levels whilst not requiring any diabetes medication to maintain this.
Weight loss is important to achieve remission, but as you’ll see below it isn’t a guarantee of success. The key factor is whether or not beta cell function can be returned. The beta cells are cells in the pancreas that produce and release insulin. In people with type 2 diabetes beta cell function is compromised because too much fat is stored in the pancreas. This loss of specialist function is called “de-differentiation”, which leads to the first phase insulin response – the ability to quickly react to an increase in glucose in the blood – being lost or delayed. In a nutshell: if you return beta cell function you can reverse type 2 diabetes.
What did this latest study look at?
In the most recent paper from the DiRECT study, a sample of the participants from the main study had a number of additional measurements taken to help establish the mechanisms of diabetes remission. The paper split the sample into responders (29 participants) and non-responders (16 participants) to try and work out what was different between the two groups.
Responders versus non-responders: similarities
Largely the groups were very similar. They lost a similar amount of weight (16.2kg in responders compared to 13.4kg in non-responders) and a similar amount of fat from their liver (13.4% v 11.9%) and pancreas (0.90% v 0.78%). Weight loss seemed to be the biggest predictor of success in the previous studies (for example this one), with the loss of fat from the liver and pancreas being necessary for diabetes remission. However, there is clearly another factor at play that explains why, despite losing a similar amount of weight and fat, the non-responders did not see a return to “normal” blood glucose levels.
Responders versus non-responders: differences
I’ve already alluded to the fact the non-responders didn’t see a return of the first phase insulin response, which is one key difference. Another potentially important difference, which might help explain this, is that the average amount of time the individuals had had type 2 diabetes was slightly longer in the non-responders (3.8 years) than in the responders (2.7 years). Previous research looking at remission of type 2 diabetes, this for example, suggests this is important.
The theory is that the longer the cells in the pancreas are exposed to elevated levels of fat, which lead to the de-differentiation described above, the more difficult it is for them to return to their specialised functions (“re-differentiation”). After a certain point they may no longer be able to do this at all, though it is important to note that there is evidence that people who have had type 2 diabetes for many years can still achieve remission (so please DO NOT interpret the 3.8 years average duration in the non-responders in this study to be a cut-point for success).
The level of fat at which beta cell function is compromised, or the amount of time after which beta cell function cannot be returned, seems to be very different for different people. For these reasons we can’t yet predict who will be a responder or a non-responder.
Practical implications: what will work?
If someone is a responder they haven’t gone past the point where their beta cells can be “fixed”. For beta cell recovery they need to lose fat from their liver and pancreas. Overall weight loss is a good predictor of this. In the DiRECT study participants lost the required weight with a very low calorie diet. This is an extreme option that can produce quick results, and if someone can then transfer onto a dietary approach they can sustain – and can as a result maintain these benefits long term – then it may well be a good option. It does need appropriate medical supervision though.
If weight loss is the key factor, which it seems to be (remember we are only talking about the responders here), then any approach that can achieve sustained weight loss can lead to the return of beta cell function and the remission of type 2 diabetes.
So, in theory at least, one size doesn’t fit all for these people.
What about the non-responders, is there any hope?
Although it cannot be completely ruled out that the non-responders in the DiRECT study would still see beta cell recovery with further weight loss, or by following an alternative intervention, it is possible that non-responders have gone past the point of no return. That is to say: no amount of weight loss, or more importantly fat loss from the liver and pancreas, is going to result in the beta cells returning to their normal function. If this is the case then the first phase insulin response isn’t coming back. For these people therefore the “one size doesn’t fit all” approach we generally champion at X-PERT Health potentially falls down. For these people the ability to effectively metabolise carbohydrates is gone, and so the only way they are going to be able to manage their blood glucose effectively is by giving their body less carbohydrate (which breaks down into glucose) to deal with.
The work of Virta in the United States, which I have previously written about, has shown that a very low carb diet can safely and sustainably lead to the remission of type 2 diabetes. This approach doesn’t rely on the return of beta cell function because the limiting of carbs means the body’s ability to deal with them isn’t as important. So for those who the weight loss approach demonstrated to be an option by DiRECT doesn’t work for: there may not be as many options, but that doesn’t mean there isn’t any hope.
So what’s the bottom line?
For “responders” one size probably doesn’t fit all. If they can lose enough weight and keep it off their body may well be able to return to a state that it can deal with consumed carbs and, consequently, manage their blood glucose levels. But for the “non-responders” there is perhaps only one solution. If the body cannot be “repaired” to be able to deal with carbs, then the restriction of carbs might well be the only way forward for managing type 2 diabetes or even putting it into remission.
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