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Beta cell failure in T2

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Tannith

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Another thread re the early stages of T2 and damage caused in them was beginning to diverge towards early damage to the beta cells so I thought this might merit a thread all to itself:
"During the first phase, which occurs six or more years before diagnosis, glucose levels remain relatively stable but insulin resistance increases along with insulin secretion.

“This is the time when relatively straightforward lifestyle changes, like increasing physical activity, changing diet, and reducing obesity, could have the biggest impact,” he says.

The second phase of progression to disease is characterized by increased beta-cell activity as the pancreas produces more insulin to compensate for insulin resistance.

Witte says prevention efforts during this period may require more aggressive lifestyle intervention along with blood-sugar regulating medications like metformin.

During the final phase toward progression, which Witte refers to as the unstable phase, insulin production drops and blood glucose levels rise dramatically and rapidly.

The study suggests that people who are generally considered to have prediabetes are in this final phase or close to it."
Edited to include this link to above article
https://www.webmd.com/diabetes/news/20090609/insulin-changes-occur-years-before-diabetes
Insulin Changes Occur Years Before Diabetes



https://www.sciencedirect.com/science/article/pii/S1550413118304467

Translating aetiological insight into sustainable management of type 2 diabetes



I now have prediabetes after reducing my BGs from a higher level with weight loss, but am still aware of the need to try to reduce my BGs further. NHS don't treat pre diabetes other than recommending weight loss. I don't think pre diabetes is taken seriously enough by governments and their health care systems.
 
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Tannith said:
Insulin Changes Occur Years Before Diabetes
Click to expand...

That's because T2 is hyperinsulinaemia ... too much insulin prompted by a too high intake of carbohydrates.

Prof Taylor may not have realised this yet but many others have.
It's not beta cell failure but disregulation.
 
Hmm, looks like I have been in this 'final phase' for 10 years now, controlled purely by my reduced carb intake. Nothing unstable about my type 2 diabetes, or my lack of need for medication.

If I don't feed the fire, it stops burning.
 
bulkbiker said:
That's because T2 is hyperinsulinaemia ... too much insulin prompted by a too high intake of carbohydrates.

Prof Taylor may not have realised this yet but many others have.
It's not beta cell failure but disregulation.
Click to expand...

I can't get the diagrams to copy paste, but you can see them if you open the link


Diagrams illustrating the progressive loss of BCF as glucose tolerance worsens. (a) The disposition index (insulin secretion/insulin resistance = ΔI/ΔG ÷ IR) is plotted as a function of the 2-hour plasma glucose concentration (2-h PG) during an OGTT in subjects with a range of glucose intolerance and body weight. If a 2-hour PG <140 mg/dL represents normal glucose tolerance (NGT), subjects in the upper tertile (2-h PG=120-139 mg/dL) have lost two-thirds of their BCF (left arrow). Subjects in the upper tertile of IGT (2-h PG=180-199 mg/dL) have lost 80%-85% of their BCF (right arrow). Thus, by the time the diagnosis of T2DM has been made, >80% of BCF is gone. Note: Leg-end for y-axis should be "ΔI/ΔG ÷ IR." (b) The natural log of the 2-hour plasma glucose concentration (2-h PG) during the OGTT is graphed as a function of the natural log of the disposition index. These two variables are strongly and linearly related (r=0.91; P<0.00001). There are no cut points that distinguish NGT from IGT from T2DM. Rather, glucose intolerance is a continuum, and subjects simply move up and down this curve as a function of the disposition index. SI units glucose conversion: mg/dL*0.05551=mmol/L. From reference [2]. BCF, β-cell function; OGTT, oral glucose tolerance test; T2DM, type 2 diabetes mellitus.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3982570/

urr Diabetes Rev. 2014 Jan; 10(1): 2–42.

Published online 2014 Jan. doi: 10.2174/1573399810666140214093600

Assessment of Pancreatic β-Cell Function: Review of Methods and Clinical Applications
Eugenio Cersosimo,1,* Carolina Solis-Herrera,1 Michael E. Trautmann,2 Jaret Malloy,3 and Curtis L. Triplitt1
 
Tannith said:
as glucose tolerance worsens.
Click to expand...

This is insulin resistance and not beta cell failure.. that's why both you and I have managed to restore beta cell function to normal levels (or at least I have because I have tested for it through the HOMA-IR testing I've had done).
It was disregulation not failure.
 
How did you get the HOMA IR testing done? What does it cost?
 
bulkbiker said:
That's because T2 is hyperinsulinaemia ... too much insulin prompted by a too high intake of carbohydrates.

Prof Taylor may not have realised this yet but many others have.
It's not beta cell failure but disregulation.
Click to expand...
So who's going to explain this to Prof Taylor! BTW I agree the beta cell failure is often inspired guesswork.
 
Off topic a little but do biotin supplements effect the hba1c results? I only take a small supplement but just wondered..?
 
IMO it's both. IR starts really early on, long before most of us are even thinking about diabetes. Beta cell failure begins around the start of the pre diabetic stage, though it varies somewhat from person to person. I say beta cell "failure" because I don't want to get embroiled in the argument as to whether the cells dedifferentiate or actually die. One way or another they are progressively knackered and cease to be able to produce enough insulin for the body to cope with its needs. At this stage T2s start to produce too little insulin rather than too much, as had been the case in the early days. Until around mid 2020's scientist thought the beta cells died, but more recent research suggests they only dedifferentiate at first, so that it is still possible for them to be recovered. IR continues, though liver IR can be reduced or reversed very quickly by substantial weight loss. Muscular IR resistance is more stubborn.
https://diabetes.diabetesjournals.org/content/53/suppl_3/S16
 
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The linked article opens with this statement
"This article proposes five stages in the progression of diabetes, " so it is a hypothesis at the moment. One thing that stem cell research did find out is that blank stem cells can indeed be programmed to act like for example beta cells, but once programmed they cannot be changed or reset to blank. So dedifferentiation is a theory that has not been proven in practice.

Beta cell mass is diffficult to do. In post mortem examinations they do histological analysis. Ths means they take a thin cross section of a pancreas, stain it and scan it optically to estimate the density of beta cells holding insulin at time of death, then multiplying this density up assuming the sample is representative of the total pancreas. Its weight is one input to the equation.

The other way is to try to use the OGTT results to estimate the amount of beta cells that have ceased to function. As has been discussed in other threads, this test expresses a value for insulin resistance, but is not a test of beta cell function per se. The fact that BMI and total body weight are used in the equation is strange.

However, if beta cells are significantly damaged by the time we are DX;ed prediabetic, then many of the medications in use today would have very little effect. We would indeed be left with only Insulin, metformin, and the gliflozins for therapy, and the sulfonylureas, incretins, and most GLUT meds would have little effect, In vivo evidence suggests otherwise. The fact that diet can be used as a major control mechanism does seem to show that beta cell function may be impaired, but the cells are not dedifferentiated nor dead.
 

Hi,

Bit of an interesting one you found in the link..
It does infer that T1 is at the tail end of these "stages?" (Graph below grabbed from the study in your link.)

Was there any more progression on this study? It seems to have been submitted back in March 2004.

 
Lainie71 said:
Off topic a little but do biotin supplements effect the hba1c results? I only take a small supplement but just wondered..?
Click to expand...

I have been supplementing with biotin for a while now and my HbA1c has come down during the time I have been taking it.
Over the last 2 weeks I have increased the amount even (to 10,000ug) and have not noticed any change in my BG readings (in fact they're lower than usual but I assume it's due to skipping a few meals here and there).
 
"As of today, the only way to test the function of beta cells is through the average C-peptide plasma concentration (CPAVE), which is a long and tedious process involving a liquid meal and numerous blood samples.17 Nov 2018"

A Simple Way to Calculate Beta Cell Functional Decline in ...
https://www.diabetesincontrol.com › Resources › Articles
 
Here are a few more links to articles on beta cell dysfunction in T2. They are much more recent.
THE FoundationS of β-Cell Failure: Dysfunction, Dedifferentiation, or Death?
β-Cell loss in response to nutrient excess and stress was traditionally felt to occur exclusively via β-cell death. Although β-cell death might be a final common pathway in the natural history of T2D, more recent evidence indicates a more complex situation in which β-cells can initiate several alternative responses to avert irreversible loss, suggesting the potential for earlier intervention.

https://care.diabetesjournals.org/content/37/6/1751

The observation that the degree of β cell dysfunction correlates with the severity of MetS highlights the need to better understand β cell dysfunction in the development of MetS

https://www.jci.org/articles/view/129188

Discussion
Our data demonstrate that β cells exhibit significant functional deterioration and exhaustion already at early stages of type 2 diabetes pathogenesis, at which subjects exhibit impaired glucose tolerance but are not yet diabetic. Conversely, β cell volume is maintained at this stage of disease progression, which is in line with the previous finding of unchanged β cell mass in impaired glucose-tolerant subjects (Meier et al., 2009). Thus, our results identify β cell dysfunction as an initial feature of diabetes development and not necessarily as consequence of a preceding loss in β cell mass.

Nevertheless, our results clearly demonstrate that, even at full-blown type 2 diabetes, there are significant numbers of dysfunctional β cells present, which potentially can be functionally recovered by appropriate therapies, e.g., via the removal of potential systemic causes for β cell dysfunction and allowing restoration of secretory capacity.

https://www.sciencedirect.com/science/article/pii/S2211124720303478
The Pathologic Basis of Disease Progression
At the diagnosis of type 2 diabetes, β-cell function is typically reduced to 50% of normal by HOMA modeling and to a greater extent on dynamic testing (1,18). Despite the initial effect of diet and oral therapy to lower glucose, observational studies have shown that disease progression is associated with inexorably declining β-cell function and progression to insulin commencement, with relatively minor changes in underlying insulin resistance. Such observations have been made in the context of continuing weight gain (19)

https://care.diabetesjournals.org/content/39/11/2080
 
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Many thanks for that I take that many vitamins I rattle
 
Yes, multiple C-peptide readings over time will provide a measure of beta cell output, and is indeed tedious and not cheap. It is a trechnique used when doing mice or lab rat studies, but have never seen it applied to human subjects in vivo. It is certainly feasible.

However, it only shows beta cell output being reduced, but it does not prove that it is a the beta cell malfunctioning It could also be an enzyme signalling issue, so to isolate this possibility then the stimulating enzymes and transport paths need to be monitored at the same time. IMO the case for beta cell malfuncton or dedifferentiation is not proven. I liken it to the windscteen washers on my car. if there is no water squirt when I press the switch, it could be a blocked jet, a severed or kinked feed pipe, it could be a fuse blown, lastly it may be a faulty pump needing its brushes replaced.
 
Tannith said:
>>>>>>
The observation that the degree of β cell dysfunction correlates with the severity of MetS highlights the need to better understand β cell dysfunction in the development of MetS<<<<<<<
Click to expand...

Or the role of MetS in beta cell output reduction? Works both ways IMO Chicken vs egg
Remember that Met S seems to precede the need for insulin therapy being initiated. Even so, we have seen examples of insulin therapy being withdrawn following successful lifestyle interventions, so it is no longer the b/all and end/all.
 
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This is happening with my T2 brother. We were diagnosed 10 years ago, within 3 months of each other. The insulin injections improved his health, helping his mental state and energy, resulting in more exercise and wiser food choices, leading to him now being able to reduce his insulin amounts. It's wonderful to witness this.
 
Oldvatr said:
I liken it to the windscteen washers on my car. if there is no water squirt when I press the switch, it could be a blocked jet, a severed or kinked feed pipe, it could be a fuse blown, lastly it may be a faulty pump needing its brushes replaced.
Click to expand...
Or simply an empty reservoir tank.
 
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