Roy Taylor on causes of T2D (Lancet podcast)

Eddy Edson

Eddy Edson

Well-Known Member
Relationship to Diabetes
Type 2
https://twitter.com/x/status/1829833615875649648

In conjunction with a new (paywalled) paper: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00157-8/abstract

"Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals."

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Summary​

Type 2 diabetes has long been thought to have heterogenous causes, even though epidemiological studies uniformly show a tight relationship with overnutrition. The twin cycle hypothesis postulated that interaction of self-reinforcing cycles of fat accumulation inside the liver and pancreas, driven by modest but chronic positive calorie balance, could explain the development of type 2 diabetes. This hypothesis predicted that substantial weight loss would bring about a return to the non-diabetic state, permitting observation of the pathophysiology determining the transition. These changes were postulated to reflect the basic mechanisms of causation in reverse. A series of studies over the past 15 years has elucidated these underlying mechanisms. Together with other research, the interaction of environmental and genetic factors has been clarified. This knowledge has led to successful implementation of a national programme for remission of type 2 diabetes. This Review discusses the paucity of evidence for heterogeneity in causes of type 2 diabetes and summarises the in vivo pathophysiological changes, which cause this disease of overnutrition. Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals.
 
JITR said:
@everydayupsanddowns

Would anyone at Diabetes UK with access to this Lancet (paywalled) paper be able to comment in a bit more detail on "Weight loss of 10–15% by any means soon after onset of type 2 #diabetes is highly likely to bring about remission of diabetes"?

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00157-8/abstract
Click to expand...

I can ask the Information Team if they have access. What sort of comment are you looking for? A clarification? The basis on which those figures have been derived? Or something else?

I have a feeling I’ve been hearing the ‘15% of body weight’ since the early Direct follow-up trials, so there may be more detail already available unpaywalled elsewhere?
 
everydayupsanddowns said:
I can ask the Information Team if they have access. What sort of comment are you looking for? A clarification? The basis on which those figures have been derived? Or something else?

I have a feeling I’ve been hearing the ‘15% of body weight’ since the early Direct follow-up trials, so there may be more detail already available unpaywalled elsewhere?
Click to expand...

It would be interesting to know if there is anything new. In particular what does it say about "any means" (other than the Newcastle/NHS Soups & Shakes) mentioned here: "Weight loss of 10–15% by any means soon after onset of type 2 #diabetes is highly likely to bring about remission of diabetes".

Now the NHS T2 Remission programme is in full swing there should be plenty of data available, but has it been published?
 
Eddy Edson said:
https://twitter.com/x/status/1829833615875649648

In conjunction with a new (paywalled) paper: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00157-8/abstract

"Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals."
Click to expand...
Very many thanks for this.

I didn't actually believe this 'homogenous' bit, the idea that there is a single cause in all cases of Type 2, as there appears to be a significant number of people who don't fit Taylor's profile of how Type 2 comes about. In particular I've read accounts of people who describe themselves as being around the middle of the 'normal' BMI range, who were diagnosed at a young age and who say there are many cases of diabetes in their family in people who are also not overweight. I found this commonality amongst such cases quite striking, this family history element. This led me to believe that Type 2 is effectively a blanket diagnosis for the typical form that most of us have along with perhaps one or more rarer forms - different diseases basically, falling under a single diagnosis as they all look the same from the outside.

In the podcast (around the 15 minute mark) Taylor does however state that some people are more sensitive to liver fat than others (presumably due to genetics). I suppose this might explain it - if there is a set of genetic traits that causes insulin resistance in the liver at lower levels of fat in that organ then presumably that would lead to families of people diagnosed young at quite low BMIs. Never having reached their 'personal fat threshold', not even having particularly fatty livers, just very sensitive to that fat.

Hopefully some day genetic testing will identify the different genetic traits involved and determine if that's the case. I would wonder if it might be possible to treat such people using one of the new drugs for fatty liver disease? This one for example, Rezdiffra, approved in the US earlier this year - Link. If a person who was incapable of losing weight in order to lower liver fat levels because they are already quite slim were prescribed such a medication, what might happen I wonder?
 
Taylor has always said that it doesn't matter how you lose the weight.
 
PerSpinasAdAstra said:
I didn't actually believe this 'homogenous' bit, the idea that there is a single cause in all cases of Type 2, as there appears to be a significant number of people who don't fit Taylor's profile of how Type 2 comes about. In particular I've read accounts of people who describe themselves as being around the middle of the 'normal' BMI range, who were diagnosed at a young age and who say there are many cases of diabetes in their family in people who are also not overweight.
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But why woud that not fall under the 'personal' part of personal fat threshold?
 
Eddy Edson said:
Taylor has always said that it doesn't matter how you lose the weight.
Click to expand...
It doesn't. And while I think that Taylor needed to go hard/extreme for the sake of the science, it's a shame that many will think that that success is specifically as a result of such an unnecessarily restrictive regime.
 
My (maternal) grandfather was underweight when diagnosed with type 2 diabetes. I don't think it was misdiagnosed type 1 as he only had insulin for 6 months following a heart attack (later on than the original diagnosis) per protocols and otherwise was managed by type 2 medications for a couple of decades until he died at 89. He was prescribed shakes in addition to meals in order to gain weight at diabetes diagnosis.

So I would definitely disagree that type 2 can always be explained by "overnutrition" unless as @PerSpinasAdAstra suggested my grandad actually had a different rare type that hasn't been identified yet so was lumped into type 2.

Interestingly both my dad and his sister have type 2, but neither of their parents was ever diagnosed diabetic as far as I know.
 
It seems to me another case where using labels gets in the way of understanding. Diabetes is poor auto blood glucose control. There is a group where this is due to autoimmune destruction of the capacity of the pancreas to produce insulin. They have the type 1 label. There is a group whose diabetes is due to wholesale loss of pancreatic function for one reason or another. They are given the Type 3c label. The rest are given a Type 2 label. Of this rest, there is a large group whose diabetes is due to fat build up through being overweight and where shedding the weight will restore normal auto glucose control. There is also a smaller group who have a normal weight to which that does not apply. Not everybody who is not T1 or T3c an be bundled into the same box and be treated the same.

So if you need labels, again it seems to me, then some more labels need to be introduced to divide up Type 2. Into categories that need different approaches to treatment. Perhaps introducing Taylorian T2 diabetes and Non-Taylorian T2 diabetes labels might be a place to start. If nothing else it might satisfy the odd ego.
 
Docb said:
It seems to me another case where using labels gets in the way of understanding. Diabetes is poor auto blood glucose control. There is a group where this is due to autoimmune destruction of the capacity of the pancreas to produce insulin. They have the type 1 label. There is a group whose diabetes is due to wholesale loss of pancreatic function for one reason or another. They are given the Type 3c label. The rest are given a Type 2 label. Of this rest, there is a large group whose diabetes is due to fat build up through being overweight and where shedding the weight will restore normal auto glucose control. There is also a smaller group who have a normal weight to which that does not apply. Not everybody who is not T1 or T3c an be bundled into the same box and be treated the same.

So if you need labels, again it seems to me, then some more labels need to be introduced to divide up Type 2. Into categories that need different approaches to treatment. Perhaps introducing Taylorian T2 diabetes and Non-Taylorian T2 diabetes labels might be a place to start. If nothing else it might satisfy the odd ego.
Click to expand...
Docb said:
... there is a large group whose diabetes is due to fat build up through being overweight and where shedding the weight will restore normal auto glucose control. There is also a smaller group who have a normal weight to which that does not apply.
Click to expand...
I think you will find a more accurate statement is something like this:

There is a large group whose diabetes is due to fat build up in the liver and pancreas. Irrespective of weight, losing around 8-15 kg will restore normal liver function in most cases. Many of these will also restore normal glucose control, dependent on the state of the beta cells in their pancreas.

See: https://www.ncl.ac.uk/media/wwwnclacuk/newcastlemagneticresonancecentre/files/Publications 2.pdf



See
 
I think my beta cells are in a bad state, diet and exercise keep it under control.
 
Docb said:
So if you need labels, again it seems to me, then some more labels need to be introduced to divide up Type 2. Into categories that need different approaches to treatment. Perhaps introducing Taylorian T2 diabetes and Non-Taylorian T2 diabetes labels might be a place to start. If nothing else it might satisfy the odd ego.
Click to expand...
Going beyond egos, if there are distinct sub-types of Type 2 with different underlying causes no cures will ever be found until the labels are created that enable research to be conducted on what exactly distinguishes the sub-types. If we're all still being told to lose weight and maintain that weight loss, exercise, eat a healthy diet and take our tablets in very many years time there might be quite a large number of sick people who go unseen by the research community in the meantime.

If the common cold were to be considered as a single illness then it would be impossible to prevent. When looked at as a set of symptoms, effects, caused by over 200 different viruses, then the common cold could largely be prevented with vaccines (if anyone could be bothered). With that analogy in mind, how many 'vaccines' do we need to eliminate Type 2 diabetes? Nobody knows, because Type 2 just means a high HbA1c while still producing insulin. That definition is about as useful when it comes to searching for better preventions and perhaps cures as defining the common cold as 'an illness characterised by having a runny nose'. In the long run I believe labels, if there are indeed sub-types to be labelled, may be quite important.
 
What rarely gets mentioned at the same time Taylor was introducing his research, Exter introduced that they had identified many distinct variations of Diabetes. I have forgotten the exact number they found but it was many, and the treatments were different.
I suspect unless we get some sort of genetic tests, the exact tye for some won't be known.
 
Eddy Edson said:
https://twitter.com/x/status/1829833615875649648

In conjunction with a new (paywalled) paper: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00157-8/abstract

"Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals."

View attachment 31405

Summary​

Type 2 diabetes has long been thought to have heterogenous causes, even though epidemiological studies uniformly show a tight relationship with overnutrition. The twin cycle hypothesis postulated that interaction of self-reinforcing cycles of fat accumulation inside the liver and pancreas, driven by modest but chronic positive calorie balance, could explain the development of type 2 diabetes. This hypothesis predicted that substantial weight loss would bring about a return to the non-diabetic state, permitting observation of the pathophysiology determining the transition. These changes were postulated to reflect the basic mechanisms of causation in reverse. A series of studies over the past 15 years has elucidated these underlying mechanisms. Together with other research, the interaction of environmental and genetic factors has been clarified. This knowledge has led to successful implementation of a national programme for remission of type 2 diabetes. This Review discusses the paucity of evidence for heterogeneity in causes of type 2 diabetes and summarises the in vivo pathophysiological changes, which cause this disease of overnutrition. Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals.
Click to expand...
Good to see in the diagram presented that Taylor accepts Type 2 is Genetic in origin, mutant genes come before 'overnutrition'. We just made a poor choice of grandparents.
 
grovesy said:
... Exter introduced that they had identified many distinct variations of Diabetes. I have forgotten the exact number they found but it was many, and the treatments were different.
Click to expand...
@grovesy
Exeter?
Do you have any reference to 'they had identified many distinct variations of Diabetes'?
TIA

P.S. Did they detail the pathogenesis, prognosis, treatments and outcome for each of these variants?
 
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JITR said:
@grovesy
Exeter?
Do you have any reference to 'they had identified many distinct variations of Diabetes'?
TIA
Click to expand...
In the 1990s there was a big fuss about Amylin in Type 2 with the suggestion that a significant proportion of Type 2s were victims of over production of Amylin and should be reclassified as 'Amylinotics'. Not heard much about that since.

In the early 2000s a researcher using powerful microscopes discovered that the Insulin Resistance in at least 20% of Type 2s was caused by stubby or nonexistent tethers on their Insulin. Meaning the Insulin could deliver Glucose to the Glucose Receptor ( a Clathryn coated pit on the cell wall ) but couldn't tether itself to the Insulin Receptor Port to signal a delivery. The Glucose eventually freed itself and was eventually stored as fat. We have not heard any follow -ups on that research either. It might entail the quality of the insulin of each new Type 2 being examined with up to 20% being possibly better off with exogenous insulin from the kick-off instead of the usual ham-fisted palliatives.

Even when I was dxed in 1992 it was generally said that Type 2 Diabetes was a bunch of conditions with a common main symptom. Now Taylor seems to be claiming it's all one thing ( without much evidence, only unproven hypotheses) and Your Mileage May NOT Vary.
 
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