Insulin resistance, beta cell dysfunction, hyperinsulinaemia, and DiRECT

[bulkbiker]

It says that they used c-peptide.

They actually used an existing method to determine insulin secretion.

Here's a paper detailing its use:

Effect of Acute Hyperglycemia on Insulin Secretion in Humans

First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can

diabetesjournals.org

I'm guessing the professors went radio silence because they don't suffer fools gladly.

Hi again

Just reading through your paper...

These tests were carried out on 13 non diabetic subjects

" Thirteen nondiabetic subjects with wide-ranging BMIs were studied" so not only nothing to do with DiRECT but also nothing to do with people with diabetes.

I'm not sure what the relevance is here.. am I missing something?

 

[Eddy Edson]

Don't you find it odd though that a study based on "insulin production" didn't test insulin production levels?
Or at the very least c-peptide as a better proxy?

It has always seemed odd to me.. also of course in the early pre trial run for DiRECT they tested for ketones but in the main trial this doesn't seem to have been done (or at least the levels haven't been reported). Again an oddity.

I have corresponded with Prof Taylor about this but once I asked him the ketone question he went radio silence.

It's impossible to ask Prof Lean anything as he becomes very offensive/defensive if anyone has a different view.

Such a shame that all the test results from the DiRECT study haven't been anonymised and released as I'm sure there is a treasure trove of data there that could be used for alternative theories,

They've reported ketones:


They've reported fasting plasma insulin levels and first-phase & maximal insulin response:


From the 2018 Cell Metabolism paper: https://www.cell.com/action/showPdf?pii=S1550-4131(18)30446-7

 

[bulkbiker]

They've reported ketones:

View attachment 23968
They've reported fasting plasma insulin levels and first-phase & maximal insulin response:

View attachment 23969
From the 2018 Cell Metabolism paper: https://www.cell.com/action/showPdf?pii=S1550-4131(18)30446-7

That is not the "official" DiRECT trial there aren't enough participants so that data is either from a subset of from one of the precursor trials.
We have no idea why those people were selected.
Plus it shows changes in insulin levels by the looks of it.. you can't have negative insulin..or the figures are meaningless. Not sure.

 

[Eddy Edson]

That is not the "official" DiRECT trial there aren't enough participants so that data is either from a subset of from one of the precursor trials.
We have no idea why those people were selected.
Plus it shows changes in insulin levels by the looks of it.. you can't have negative insulin..or the figures are meaningless. Not sure.

Yes, they show differences.

Read the paper for the subgoup details.

 

[bulkbiker]

Yes, they show differences.

Read the paper for the subgoup details.

Unfortunately doesn't really help with the key question.. were they hyperinsulinemic..?

I'll read in details a bit later thanks for the link though.

Quite interesting that the presence of ketones was recorded.

 

[Eddy Edson]

Unfortunately doesn't really help with the key question.. were they hyperinsulinemic..?

I'll read in details a bit later thanks for the link though.

Quite interesting that the presence of ketones was recorded.

Check Fig 4F and the beta-cell commentary for absolute fasting insulin levels.

 

[bulkbiker]

Check Fig 4F and the beta-cell commentary for absolute fasting insulin levels.

Interesting.. just goes to show what a treasure trove of data is contained within the study results that we will never see..

Ketone data and insulin data.. looks like the non responders might have been misdiagnosed as T2 with lower than "normal" production ?

Shame it can't be anonymised and released for us all to play with..

Does diabetes.org.uk own it I wonder ?


@everydayupsanddowns do you know or could you ask ?

 

[Burylancs]

Interesting.. just goes to show what a treasure trove of data is contained within the study results that we will never see..

Ketone data and insulin data.. looks like the non responders might have been misdiagnosed as T2 with lower than "normal" production ?

Shame it can't be anonymised and released for us all to play with..

Does diabetes.org.uk own it I wonder ?


@everydayupsanddowns do you know or could you ask ?

Was there actually a peer reviewed academic paper about the original 2017 Direct trial published at all ? Most of what I can find is a raft of claims and assertions about it unsupported by any evidence.

The daftest claim from Taylor is that he had T2s on a diet for three months in which they were getting up to 20% of their nutrition from Fresh Air ( 50% cals from carbs. 20-30% from fats and 10-20 % from protein).

 

[bulkbiker]

Was there actually a peer reviewed academic paper about the original 2017 Direct trial published at all ? Most of what I can find is a raft of claims and assertions about it unsupported by any evidence.

This page has all the publications.. there appear to have been many! I'd assume that some of the journals would require peer review...

Direct Trial

www.directclinicaltrial.org.uk

 

[Burylancs]

This page has all the publications.. there appear to have been many! I'd assume that some of the journals would require peer review...

Direct Trial

www.directclinicaltrial.org.uk

In most of those Direct is just mentioned in passing snd in the footnotes. No clear cut account of Direct with comparative charts of Intervention vs Control Group for example. And of course the Direct study was statistically incompetent. Practices had been randomly allocated to Intervention or Control and so practices not the individuals within them should have been assessed. Baaad Science

 

[bulkbiker]

Practices had been randomly allocated to Intervention or Control and so practices not the individuals within them should have been assessed.

Very good point and one that I hadn't really thought of before..

 

[Deleted member 21371]

His MBE for services to Diabetic Research suggests otherwise.
(So does my pizza, fully reversed on a sample of 1)

 

[Drummer]

I don’t care what your view is.

The majority of people with T2 have both insulin resistance and a certain amount of beta cell dysfunction, and this is the phenotype considered as ‘classic’ T2 in most research.

If most type 2s are never tested for either condition I am not sure how that claim can be made or any conclusion reached about the frequency within those diagnosed.

 

[everydayupsanddowns]

In most of those Direct is just mentioned in passing snd in the footnotes. No clear cut account of Direct with comparative charts of Intervention vs Control Group for example. And of course the Direct study was statistically incompetent. Practices had been randomly allocated to Intervention or Control and so practices not the individuals within them should have been assessed. Baaad Science

A cluster randomised controlled trial is a completely valid trial structure. I can’t agree with your assessment that it is somehow incompetent.

Some questions and interventions are just better suited to this kind of structure.

The trial protocol is here which details the methods

https://www.directclinicaltrial.org.uk/Pubfiles/ProtocolForAClusterRandomisedTrial.pdf

 

[Deleted member 21371]

Maybe there is some confusion and thinking of the Dr Unwin.
He had no control group, just a study of some of his patients who apparently performed well, and reported their diet to him, on a hearsay basis?
(Which is still worth trying for some, if it works)

 

[everydayupsanddowns]

Shame it can't be anonymised and released for us all to play with..

Does diabetes.org.uk own it I wonder ?


@everydayupsanddowns do you know or could you ask ?

As you suggest, access to raw trial data is usually limited by confidentiality agreements with participants.

As I understand it contacting the primary study author(s) is generally the way to request access to parts of trial data sets for analysis? The list of publications linked above suggests that further analysis has already taken place.

This is the authors’ version of the initial paper, and has the tables / figures that were then published in the Lancet @Burylancs if that helps?

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial - Enlighten Publications

eprints.gla.ac.uk

 

[childofthesea43]

Maybe there is some confusion and thinking of the Dr Unwin.
He had no control group, just a study of some of his patients who apparently performed well, and reported their diet to him, on a hearsay basis?
(Which is still worth trying for some, if it works)

In the journal BMJ Nutrition, Prevention and Health, Dr Unwin explains the methodology in detail, which was clearly more structured and deliberative than might be suggested by the wording above.

 

[Deleted member 21371]

In the journal BMJ Nutrition, Prevention and Health, Dr Unwin explains the methodology in detail, which was clearly more structured and deliberative than might be suggested by the wording above.

I read it in detail at the time.
It was voluntary, and "128 (27%) of the practice population with T2D and 71 people with prediabetes had opted to follow a lower carbohydrate diet for a mean duration of 23 months".
So it was a biased group, already with incentive to improve their condition, and no great feedback on the actual food consumed, just a general diet sheet to follow, which originally did suggest limits on consumption.
But even hit or miss, it provides a good insight into the fact diabetes in reversible, or at least diet controlled in some cases.

 

[childofthesea43]

I read it in detail at the time.
It was voluntary, and "128 (27%) of the practice population with T2D and 71 people with prediabetes had opted to follow a lower carbohydrate diet for a mean duration of 23 months".
So it was a biased group, already with incentive to improve their condition, and no great feedback on the actual food consumed, just a general diet sheet to follow, which originally did suggest limits on consumption.
But even hit or miss, it provides a good insight into the fact diabetes in reversible, or at least diet controlled in some cases.

Exactly so, not a scientific experiment but a valuable demonstration of what is possible.

 

[Deleted member 21371]

Exactly so, not a scientific experiment but a valuable demonstration of what is possible.

Precisely, whereas the Direct trails were a much larger controlled study, hence maybe the confusion?
Either way, it all adds to the knowledge of what type 2 is.