Interesting report on insulin and weight loss

[Oldvatr]

https://pubmed.ncbi.nlm.nih.gov/3546350/

One thing to note is that weight loss can improve insulin response, BUT it does not change the c-peptide response, so the research seems to show that the weight loss improved insulin sensitivity in the body rather than improve beta cell function. This is at odds with the claims being made for the Newcastle Diet. Also the weight loss required was 20%.

 

[Oldvatr]

Looking at the results of the Newcastle Study Counterpoint, it is noticeable that the measured readings of C-peptide fell away during the trial period and reached a point where they were significantly lower than the control group (non diabetics). So the claims made in that study that beta cell output improved seem to be at odds with the results. It seems insulin sensitivity in the body improves as the weight dropped off, showing an improvement in reducing Insulin Resistance. Where this occurs is probably general, and not necessarily from the pancreas or the beta cells.

 

[Ronancastled]

It was the Direct 2 Year follow that reported normalising of 2nd phase (maximal) response after 12 months & remaining level at 2 years.
https://diabetes.diabetesjournals.org/content/68/Supplement_1/66-OR
The report you quote was 1987 vs 2019 for Direct follow up so not sure if measurements or tools changed much in 32 years.

 

[Oldvatr]

It was the Direct 2 Year follow that reported normalising of 2nd phase (maximal) response after 12 months & remaining level at 2 years.
https://diabetes.diabetesjournals.org/content/68/Supplement_1/66-OR
The report you quote was 1987 vs 2019 for Direct follow up so not sure if measurements or tools changed much in 32 years.

The techniques used are not very sophisticated. They probably age quite well. Technique was developed in rodent studies a long time ago. Maybe the use of a computer helped with the calculations. Taylor used a software package called ISEC.

 

[Oldvatr]

Interesting that Roy Taylor reports a 15% improvement in maximal insulin secretion over the two year period and that it corresponds to a 15% loss of weight. coincidence? Note also that Taylor reports that of the remaining responders at 2 years who had maintained their weight since the 1 year review showed no change in this parameter as well. Weight Static AND insulin output static.

 

[Lamont D]

Why is my condition, dependent on first insulin response to stop my pancreas overshoot, which means I don't get another excess of insulin?
Limiting my insulin to not have surplus insulin circulating is good for me.
And why was my health getting worse and I was gaining weight on a reduced calorie diet? (Eat well)
And why did the weight drop off, within a couple of months on a very low carb diet?
Where does all the useless excess insulin go?

Why does a T1 go hypo?, why does a T2 on insulin go hypo?, why do I go hypo?

Interesting!

 

[lucylocket61]

Why is my condition, dependent on first insulin response to stop my pancreas overshoot, which means I don't get another excess of insulin?
Limiting my insulin to not have surplus insulin circulating is good for me.
And why was my health getting worse and I was gaining weight on a reduced calorie diet? (Eat well)
And why did the weight drop off, within a couple of months on a very low carb diet?
Where does all the useless excess insulin go?

Why does a T1 go hypo?, why does a T2 on insulin go hypo?, why do I go hypo?

Interesting!

why do I, a t2 diet only, go under 3? delayed liver function maybe?

 

[Lamont D]

why do I, a t2 diet only, go under 3? delayed liver function maybe?

It all depends on how and when you go hypo?

 

[lucylocket61]

It all depends on how and when you go hypo?

So far there is no pattern unfortunately.

 

[Daibell]

I'm a ND skeptic

 

[ickihun]

Why is my condition, dependent on first insulin response to stop my pancreas overshoot, which means I don't get another excess of insulin?
Limiting my insulin to not have surplus insulin circulating is good for me.
And why was my health getting worse and I was gaining weight on a reduced calorie diet? (Eat well)
And why did the weight drop off, within a couple of months on a very low carb diet?
Where does all the useless excess insulin go?

Why does a T1 go hypo?, why does a T2 on insulin go hypo?, why do I go hypo?

Interesting!

Plain and simple. The quality of insulin at the same time as fat cells being developed as new or as existing poor quality fat in the cell. Blocking insulin pathway or not. I found made sense to my situation of the momentum of losing and needing half amount of insulin instantly. On a sliding scale in surgery and in recovery from full bypass. Then instructed by Endocrinologist to half dosage compared to pre-op usage. I was doubtful but no in fact I was close to hypos so reduced again and again. Even though at that point I only lost few pound. As I reduced my insulin so did my muscle mass and fat storage. Still had empty fat cells but needed less insulin.
I still hv all the fat cells and skin cells from pre-op but many are empty.
C-peptide is a different measure. No fat nor what status of loss/adding/ same weight gain status.
Myself I needed taylored treatment plan. So many different variables as no size fits all approach to a type2. I customised my plan on top of Endocrologists as I knew my bodies history.
One day I'm tempted to make a more advanced flow chart for care!
I'm on no insulin therapy now but mostly because I could block fat building cells so I could reduce insulin injected. On a continuous basis.
Its true the bypass is just a tool. Used the right way and anything is possible. I didn't count calories nor fat whilst losing. Just volume and good quality protein. Hence its sustainable. On-going research only dabbles with sustainability. Maybe because its not known catagorically.
I needed that more than weight loss.
@Lamont D once your cells are full where does the excess go? That answer is your answer too. I can get reactive hypos if I don't eat right. I was aware of the risk after a compromised digestive system. Like you my solution is dietary alone. No food no RH.

 

[Oldvatr]

It was the Direct 2 Year follow that reported normalising of 2nd phase (maximal) response after 12 months & remaining level at 2 years.
https://diabetes.diabetesjournals.org/content/68/Supplement_1/66-OR
The report you quote was 1987 vs 2019 for Direct follow up so not sure if measurements or tools changed much in 32 years.

This is what that report says
"Conclusion: Provided weight regain is minimized, remission of type 2 diabetes is durable over 2 years, with a gradual increase to normal beta cell functional mass."
Where did he measure beta cell mass? It is not reported in DIRECT study.

The DIRECT study report does not actually say that all the responders were tested with the glycemic clamp technique. Instead the report seems to link out to a smaller 11 participant trial he did with a small subset of the trial cohort , and the results seem to have been copied from that smaller trial, along with the protocol details to infer that it was applied to all the participants. I do not think it was. The smaller study does indeed show graphs of the first stage Insulin response recovering, which is not in the DIRECT reports. Also the small study includes tables of data which has been omitted in DIRECT.

As I pointed out above, the follow on report describes that only those responders who maintained their weight showed no change in insulin secretion. So not only did the beta cell output remain constant, but also the weight. If there is any link between insulin secretion rate and body weight then this invalidates the claims being made here

 

[Ronancastled]

Where did he measure beta cell mass? It is not reported in DIRECT study.

Unless he was cutting them open there's no way to know for sure.
Also, with the inulin secretion readings, is he measuring C-peptide levels during an OGTT, I don't know.
Where the theory of beta cell dedifferentiation is plausible, it's just a theory.
Others have theorized that it may be the remaining beta cells working harder.

This was he earlier trial to Direct, back in 2011 it was called Counter[something].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/

Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2)

So which is it, is it 8 weeks or 12 months ????

 

[Oldvatr]

Unless he was cutting them open there's no way to know for sure.
Also, with the inulin secretion readings, is he measuring C-peptide levels during an OGTT, I don't know.
Where the theory of beta cell dedifferentiation is plausible, it's just a theory.
Others have theorized that it may be the remaining beta cells working harder.

This was he earlier trial to Direct, back in 2011 it was called Counter[something].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/



So which is it, is it 8 weeks or 12 months ????

Counterpoint was 8 weeks intervention then maintenance for a year.
Roy did not do OGTT, but used an insulin clamp procedure instead. He actually did two experiments at the same time, insulin response to step increase in infused glucose (IVGTT), followed by a beta cell maximum secretion test. Both these tests are common laboratory tests used in rodent trials, but cannot be done in the context of Counterpoint or DIRECT settings.

The Beta cell dedifferentiation theory relies on the ND studies proving that the intervention actually led to an increase in beta cell output following its recovery. He ignores insulin Resistance changes in his reports, and dives straight into this new theory. He is currently fund raising to fund this new research and has published a prospective study paper in preparation of it. It is his reliance on the ND data that I am questioning, since it seems to be built on sand and I have evidence that seems to support this. I am working to find out how strong this evidence is and I have corresponded with Roy Taylor, but to date have received no response.

 

[Ronancastled]

Counterpoint was 8 weeks intervention then maintenance for a year.
Roy did not do OGTT, but used an insulin clamp procedure instead.

He did an OGTT at the 12 week follow up on Counterpoint & they stunk the place out

https://link.springer.com/article/10.1007/s00125-011-2204-7

I always use this PDF as reference to all the full Taylor studies
https://www.ncl.ac.uk/media/wwwncla...ncecentre/files/Web list of reversal publ.pdf

One wonders if he waited 12 months as per the Direct data would their OGTT results been better.

 

[Oldvatr]

He did an OGTT at the 12 week follow up on Counterpoint & they stunk the place out

https://link.springer.com/article/10.1007/s00125-011-2204-7

View attachment 52146

I always use this PDF as reference to all the full Taylor studies
https://www.ncl.ac.uk/media/wwwnclacuk/newcastlemagneticresonancecentre/files/Web list of reversal publ.pdf

One wonders if he waited 12 months as per the Direct data would their OGTT results been better.

The report you quote in this post is the small 11 participant trial that did the insulin secretion tests that i was referring to earlier. it was seperated from the main trial because it needed prompt lab assay of the drawn bloods. I believe this was repeated at 1 year and 2 years to give the results quoted in Counterpoint, and DIRECT.

 

[Oldvatr]

One thing I find surprising in the Springer report is that the fasting bgl had dropped to 'normal' levels within the first 7 days of the intervention starting. There seems to be no liver dump or DP effecting the fasting levels. Looking at Table 3, the c=peptide levels fall over the 8 week period, implying that the pancreas is reducing insulin production as the weight falls off. So the improvement in insulin response does not seem to be due to higher output of insulin. But the insulin secretion rate increases over the 8 weeks so not sure what is going on there.

The other very strange thing I see is that the insulin graph drops off very quickly (30 minutes). Looking at other GTT graphs from other studies, then the time period of insulin output seems to be very different.
https://journals.physiology.org/doi/full/10.1152/ajpregu.00650.2010

Edit to add: I suppose that since he is only interested in the maximum secretion rate, then the basal clearance is of no further interest to him.

 

[Oldvatr]

Just found some new information. Insulin Response is biphasic, and has two distinct phases. Phase one is a fast acting response, and only lasts about 10 minutes. The Second phase is the basal phase which lasts between 2 and three hours. It also decays slowly.

Arginine is used in rodent studies because it inhibits the second phase response. Clobbers it completely until bgl level reaches 10 mmol/l. and max secretion occurs at bgl>16.7 mmol/l. so Roy Taylor is only measuring phase 1 response even though he shows 2 phases on his plots. It is two consecutive IVGTT tests,and he has not allowed the body enough time to recover from the first strike IMO.

The second thing I found is that the secretion he is measuring is not Beta Cell output. The pancreas stores insulin in hexameric form i,e, 6 molecules at a time, and holds these in granules within the beta cell. It holds a supply ready for when glucose comes along, hence the quick response. It is this output that Roy Taylor measures in the ND study The problem with ectopic fat in the pancreas is that it reduces the ability to store the insulin, Less granules bein stored, less beta cell mass.

Last gem I found, rodents have two forms of insulin (insulin 1 and Insulin 2) which do different things and so are not refletive of the human endocrine system. Mice studies suck!

 

[Outlier]

Fascinating info! Thanks for sharing.

 

[MrsA2]

Most of this is above my understanding, and I look forward to a simply worded summary at the end of your investigations

Meanwhile I thank you for the new (to me) words 'biphasic' and 'hexameric' which I look forward to using in my daily Scrabble games shortly