Roy Taylor on causes of T2D (Lancet podcast)

[JITR]

The most current available data is for the period up to end 2022: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00194-3/fulltext

Findings​

Between Sept 1, 2020, and Dec 31, 2022, 7540 people were referred to the programme; of those, 1740 started TDR before January, 2022, and therefore had a full 12-month opportunity to undertake the programme by the time of data extraction at the end of December, 2022. Of those who started TDR before January, 2022, 960 (55%) completed the programme (defined as having a weight recorded at 12 months). The mean weight loss for the 1710 participants who started the programme before January, 2022 and had no missing data was 8·3% (95% CI 7·9–8·6) or 9·4 kg (8·9–9·8), and the mean weight loss for the 945 participants who completed the programme and had no missing data was 9·3% (8·8–9·8) or 10·3 kg (9·7–10·9). For the subgroup of 710 (42%) of 1710 participants who started the programme before January, 2022, and also had two HbA1c measurements recorded, 190 (27%) had remission, with mean weight loss of 13·4% (12·3–14·5) or 14·8 kg (13·4–16·3). Of the 945 participants who completed the programme, 450 (48%) had two HbA1c measurements recorded; of these, 145 (32%) had remission, with mean weight loss of 14·4% (13·2–15·5) or 15·9 kg (14·3–17·4).

Interpretation​

Findings from the NHS T2DR programme show that remission of type 2 diabetes is possible outside of research settings, through at-scale service delivery. However, the rate of remission achieved is lower and the ascertainment of data is more limited with implementation in the real world than in randomised controlled trial settings.

Lots of missing data, but short term adherence & therefore outcomes maybe a bit disappointing.

At five years, there's no reason to expect that it will be much different to any other lifestyle program (low carb, low fat, whatever: low long term adherence, maybe 5% remission rates?

@Eddy Edson
Published: September 2024 !!!
I'll reserve comment until I've read it.
Thanks.

 

[Foz556]

I was on 1000mg of metformin initially.
I lost 3 stone in weight and cut the 'bulk' carbs (Still occasionally ate potatoes and oats.)
Metformin was cut after 3 months to 500mg as hba1c was 36
I kept the weight off and hb1ac remained in the 30s, even when I introduced more carbs to my diet.
So they stopped the last 500mg of metformin this year and the next blood test was lower than the previous one.

Meals consist of veg and meat (Chicken and fish mainly) but will small portions of things like chips and seem to be able to handle potato and oats without an issue now. Occasionally have a burger (With bun). If I go out I sometimes don't restrict myself at all, and in the two weeks before my last hba1c I ate normally (As I was on holiday!)

I also do a walk every day, but I was doing that already when I was diagnosed.

Thank you for this - interesting that metformin got you down but then you were able to maintain with diet and exercise. I desparately want to get to a non-diabetic range but also don't want to take medication. Food for thought though....

 

[beating_my_betes]

My (maternal) grandfather was underweight when diagnosed with type 2 diabetes.

But it's possible to be underweight while being over-fat. While more commonly known as being skinny-fat, this situation can arise when people lose too much weight too quickly, with a commensurate loss of muscle. But in the case of those of a more advanced age, it's certainly possible to have lost muscle and bone mass, while still carrying more fat than would be proportionate to such an amount of lean mass.

Without deeper testing, preferably including a DEXA scan, it's not possible to have much more than a guess at the proportions of fat and lean mass tissue. But even if it's not a case of being skinny-fat, any of this seems to be able to be explained by the "personal" aspect of 'personal fat threshold'. Given that there are people who are non-diabetic while being over 400lbs (their personal fat threshold seemingly much higher than most), it could be a possibility that there are others at the opposite extremes, who would start accumulating ectopic fat with only a small amount of excess fat.

 

[harbottle]

Thank you for this - interesting that metformin got you down but then you were able to maintain with diet and exercise. I desparately want to get to a non-diabetic range but also don't want to take medication. Food for thought though....

I don't think the Metformin was doing anything to be honest. It was the weight loss and diet that got it down. I was only ever on a low dose, despite a high hba1c, and when I stopped taking it there was no change in hba1c.

 

[42istheanswer]

But it's possible to be underweight while being over-fat. While more commonly known as being skinny-fat, this situation can arise when people lose too much weight too quickly, with a commensurate loss of muscle. But in the case of those of a more advanced age, it's certainly possible to have lost muscle and bone mass, while still carrying more fat than would be proportionate to such an amount of lean mass.

Without deeper testing, preferably including a DEXA scan, it's not possible to have much more than a guess at the proportions of fat and lean mass tissue. But even if it's not a case of being skinny-fat, any of this seems to be able to be explained by the "personal" aspect of 'personal fat threshold'. Given that there are people who are non-diabetic while being over 400lbs (their personal fat threshold seemingly much higher than most), it could be a possibility that there are others at the opposite extremes, who would start accumulating ectopic fat with only a small amount of excess fat.

He didn't have excess fat. He was significantly underweight

 

[Foz556]

I don't think the Metformin was doing anything to be honest. It was the weight loss and diet that got it down. I was only ever on a low dose, despite a high hba1c, and when I stopped taking it there was no chance in hba1c.

Sorry yes I jumped to conclusions there! Thanks for clearing that up 🙂

 

[Burylancs]

The range of weight loss for remission from Taylor's studies is approx 10% - 15%. Lower end for people with normal-ish BMI, higher end for people with obesity.

For me, starting at BMI ~25, the magic number was around 10%.

These percentages are averages - so for example some people with obesity in the DiRECT trial got to remission with less than 15% weight loss. It's interesting to note that at the 5 year mark, it seems like the only people who maintained weight loss sufficient to maintain remission were these 10-percenters.

When I was dxed in 1992 all the literature said losing just 10% of weight significantly improved insulin resistance and control. That Was based on the researches in the 1950s by a chap whose name I have forgotten. But from the 1950s onwards in the NHS and the British Diabetic Association ( now trading as Diabetes UK) the advice was to lose weight by any means and keep it off. I think Taylor's gone back to that traditional message after the failure of his crash diet in the DiRECT study. And of course it was established early doors that going on a diet was a predictor of weight gain. So the traditional advice was always to look for a sustainable change of diet and lifestyle by baby steps.

 

[JITR]

When I was dxed in 1992 all the literature said losing just 10% of weight significantly improved insulin resistance and control. That Was based on the researches in the 1950s by a chap whose name I have forgotten. But from the 1950s onwards in the NHS and the British Diabetic Association ( now trading as Diabetes UK) the advice was to lose weight by any means and keep it off. I think Taylor's gone back to that traditional message after the failure of his crash diet in the DiRECT study. And of course it was established early doors that going on a diet was a predictor of weight gain. So the traditional advice was always to look for a sustainable change of diet and lifestyle by baby steps.

I agree with all the underlying points in your post except your oft repeated personal attack on Professor Taylor.

 

[Burylancs]

I agree with all the underlying points in your post except your oft repeated personal attack on Professor Taylor.

I haven't made a 'personal attack' on anybody. Wasn't I implying that Taylor was being rather sensible in returning to the traditional messaging ? 'Lose weight by any means and keep it off'.

 

[harbottle]

I haven't made a 'personal attack' on anybody. Wasn't I implying that Taylor was being rather sensible in returning to the traditional messaging ? 'Lose weight by any means and keep it off'.

Isn't that what he's always said?

His research shows that weight loss can improve insulin response in some people in the short term, but regaining weight stops it again, which is what his 'model' (That twin cycle thingy) predicts.

 

[Burylancs]

Isn't that what he's always said?

His research shows that weight loss can improve insulin response in some people in the short term, but regaining weight stops it again, which is what his 'model' (That twin cycle thingy) predicts.

No that's not what he has always said. When he first came on the scene (2007?) his message was that a diagnosis of Type 2 Diabetes should be treated as a medical emergency with the patient put on to a medically supervised diet for six weeks or more. Then he developed the idea that a Crash Diet which had to be low calory( he used the Cambridge Diet of shakes and bars that has been around for yonks) would clear the fat from the pancreas and liver. It had to be a crash diet, an immediate effect. That was the innovation. And that's what DiRECT tested. But low calorie crash diets have failed to deliver except in the short term. The advantages wash out over time as the fundamentals of the condition, the Metabolic Syndrome and Insulin Resistance, reassert themselves. He's even started flirting with low carb hasn't he ?

 

[JITR]

Burylancs said:
I haven't made a 'personal attack' on anybody. Wasn't I implying that Taylor was being rather sensible in returning to the traditional messaging ? 'Lose weight by any means and keep it off'.

The 'crash diet' succeeded in reversing fatty liver and fatty pancreas for many participants in the first 3 months of the DiRECT study. Their GPs failed to provide adequate support for most of their patients to sustain their weight loss year on year.

After the COUNTERPOINT study in c.2008 Professor Taylor called for research into optimum ways to achieve and sustain the weight loss necessary for full remission, and recommended individuals adopt some form of portion control not soups and shakes. Since then members of this forum and many others, including me, have worked out how to do that for themselves, by all sorts of means.

Nevertheless I hope the NHS Remission pathway which stemmed from DiRECT will prove to be a long term success for many participants.

 

[harbottle]

I don't tend to bother about the ins and outs of the subsequent failure of people to keep the weight off. Most people who diet to lose weight regain it anyway, so it's no surprise.

I was more interested in the measurements show how the first phase insulin response was restored and the 2nd phase was stronger after/during the initial weight loss and calorie reduction.

 

[Burylancs]

I don't tend to bother about the ins and outs of the subsequent failure of people to keep the weight off. Most people who diet to lose weight regain it anyway, so it's no surprise.

I was more interested in the measurements show how the first phase insulin response was restored and the 2nd phase was stronger after/during the initial weight loss and calorie reduction.

Can you direct us to a study that showed that first phase insulin response was restored please ?

 

[harbottle]

Can you direct us to a study that showed that first phase insulin response was restored please ?

It's detailed in the papers Taylor wrote. One had scans of the pancreas showing how its shape changed (Withered to non-withered) and how 'responders' saw first phase insulin response normalise.

Given you're so critical of his work, I'm surprised you haven't actually read it.

Here's at least one (From Counterpoint):

Calorie restriction for long-term remission of type 2 diabetes

Starting with a hypothesis which postulated a simple explanation arising from the basic cause of type 2 diabetes, a series of studies has introduced a paradigm shift in our understanding of the condition. Gradual accumulation of fat in the liver and pancreas ...

www.ncbi.nlm.nih.gov

The results were clear-cut: individuals with very ordinary type 2 diabetes (up to 4 years duration) regained absolutely normal fasting glucose levels within 7 days of commencing a very low calorie diet. This was despite stopping metformin therapy on day one of the diet. Liver fat levels dropped by 30% and liver insulin sensitivity returned to normal in the first 7 days, explaining the change in fasting plasma glucose. However, the change in insulin secretion followed a different time course, gradually improving to normal over 8 weeks. The main data from Counterpoint are illustrated in Fig Fig22.

This paper also has more:

https://www.ncl.ac.uk/media/wwwnclacuk/newcastlemagneticresonancecentre/files/Taylor%20et%20al%20Cell%20Metabolism%202018.pdf

First-phase insulin secretion increased in responders after weight loss from 0.04[-0.05--0.32] to 0.11[0.0005--0.51] nmol/min/m2 (p < 0.0001), whereas no change was observed in the non-responders (0.02[-0.07-0.13] to 0.01[-0.04- 0.05] nmol/min/m2, p = 0.96; Figure 5A; Table 2). In the responders, increased first- phase insulin secretion was maintained

During the course of the study they measured insulin response and took scans of the pancreas. I believe they also gave people OGTT and they passed it with results in the 6s at the two hour mark.

The find here was that in 'responders', the beta cells started working again and were not dead, or had not undergone apoptosis, which matched the predictions of Taylor's twin cycle hypothesis model.

I just did a quick google, but I'm sure there are more.

 

[JITR]

Here is a list of Roy Taylor's publications: https://eprints.ncl.ac.uk/author/61164

The Banting Lecture 2012 is informative but take your pick.

 

[harbottle]

Here is a list of Roy Taylor's publications. The Banting Lecture 2012 is informative but take your pick.

I think you forgot to put the list in!

 

[PerSpinasAdAstra]

Can you direct us to a study that showed that first phase insulin response was restored please ?

Presentation slides from the Newcastle University website associated with the DiRECT trial which has the insulin response recovery graphs - Link (PDF file). Partially restored, not fully restored, and it didn't budge in the 'non-responders' so the partial recovery definitely doesn't occur for everyone.

 

[JITR]

I think you forgot to put the list in!

Now added. Here is a list of Roy Taylor's publications: https://eprints.ncl.ac.uk/author/61164

Thanks.

 

[harbottle]

Presentation slides from the Newcastle University website associated with the DiRECT trial which has the insulin response recovery graphs - Link (PDF file). Partially restored, not fully restored, and it didn't budge in the 'non-responders' so the partial recovery definitely doesn't occur for everyone.

Yes, partially restored first phase that returns quickly and improves over time and a 2nd phase that improves over a longer period time - I believe the assessment of beta cells is that the cells are restored to full functionality and the 'withered' edges seen with T2 are smoothed out. What is important is that the improved response allowed the 'responders' to return to a 'normal' diet and pass an OGTT.

There's also, I believe, a direct relationship to fasting glucose and first phase - in responders fasting glucose went back to normal as first phase response returned. In non-responders fasting glucose remained high.