8 causes of diabetes

[VictorVillalobos]

Hi Guys, I am starting this new thread because some of you out there were discussing already to move forward from the simple paradigm of muscle insulin resistance, liver insulin resistance and insufficient insulin production.

Here is a more sophisticated model: the eight causes of diabetes. I would like to ask people here, especially those who seem to have nailed down their management of blood glucose,

a. Have you identified which problems you have behind your high blood glucose?
b. If so, how did you did it?
c. What was the solution you used?

The eight causes, as explained by Dr DeFronzo in the lecture he gave when obtaining the 2008 Banting memorial prize are:

1. Muscle insulin resistance
2. liver insulin resistance
3. B cell disfunctiona first phase insulin secretion and insufficient insulin secretion
4. Fat cell accelerated lipolysis
5. incretin deficiency/resistance in the intestine
6. Hyperglucagonemia or disfunction of the alpha cells in the pancreas
7. increased glucose reabsortion in the kidney
8. Dysfunctional Brain messaging (for example insulin resistance)

Here are two links to overview the model.
A short video: https://www.novomedlink.com/profess...ous-octet-core-defects-in-type2-diabetes.html
The paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661582/

I just emailed to verify if he had major changes to this model from 2008. Will keep you posted.

 

[chalup]

I do not see hyperinsulinemia on that list and it is a major player driving insulin resistance and beta cell toxicity. Great list though and glad to not see fat and lazy on there.

 

[kokhongw]

All these seems to be symptoms rather than causes...

The "cause" would be what triggers the insulin resistance through the various system.
Liver, Muscles, Brain.

Is it the chronically elevated insulin levels triggered by high carbs/fructose diets?
Is it the other chemically induced endocrine disruptions that reduced FGF1 protein?

 

[VictorVillalobos]

Hi,

All these seems to be symptoms rather than causes...

The "cause" would be what triggers the insulin resistance through the various system.
Liver, Muscles, Brain.
Is it the chronically elevated insulin levels triggered by high carbs/fructose diets?
Is it the other chemically induced endocrine disruptions that reduced FGF1 protein?

All these seems to be symptoms rather than causes...

The "cause" would be what triggers the insulin resistance through the various system.
Liver, Muscles, Brain.

Is it the chronically elevated insulin levels triggered by high carbs/fructose diets?
Is it the other chemically induced endocrine disruptions that reduced FGF1 protein?

I do not see hyperinsulinemia on that list and it is a major player driving insulin resistance and beta cell toxicity. Great list though and glad to not see fat and lazy on there.

I believe there is more agreement on this order. muscle ins resistance -> increased insulin production --- hyperinsulinemia. Although of course, there are and can be many other causes for hyperinsulinemia.

The point is, though, that as far as one has muscle insulin resistance, one is giving a hell of a time to the pancreas.

Now, what can reduce muscle insulin resistance? A great physical activity program, culminating in high intensity training is my first choice.

Main causes of muscle insulin resistance? Well many many. As
kokhongw above "high carbs/fructose diets". "chemically induced endocrine disruptions". Which is also another Banting lecture....
Corkey, B.E., 2012. Hyperinsulinemia: Cause or Consequence? Banting Lecture 2011. Diabetes 61, 4–13. doi:10.2337/db11-1483

 

[Brunneria]

Speaking from my personal perspective, I have IR from several different causes, which led to T2.
But I don't have enough techno-speak to determine whether they are already included on your list.

Here they are, in the order that I think they appeared:

Age 4 - Reactive hypoglycaemia (excess insulin response to carbs and/or insufficient glucagon, unsure which, or if there are other factors involved)
Age 12-16 - onset of polycystic ovary syndrome
Age 16-18 - development of prolactinoma
Age 15-25 - significant weight gain
Age - 30ish - belated diagnosis of prolactinoma and prescription of Cabergoline - known to increase insulin resistance
Age 40+ - development of type 2 diabetes

It would take a great deal more medical knowledge than I have to know which of my list relates to which of your list...

 

[kokhongw]

@VictorVillalobos

Thanks this is a great link discussing hyperinsulinemia.

Corkey, B.E., 2012. Hyperinsulinemia: Cause or Consequence? Banting Lecture 2011. Diabetes 61, 4–13. doi:10.2337/db11-1483

I totally agree with this observation. And that is why medication like glipizide and sulfonylureas should be used with caution.

Validation of b-cell–mediated insulin resistance via hypersecretion would lead to radically different and novel
strategies for the treatment of insulin resistance and type2 diabetes. Such validation would suggest possible early
interventions for prevention of basal hypersecretion rather than early interventions that stimulate even more
insulin secretion. It may even be possible to use natural non toxic extracellular metabolites or diet to modulate
intracellular signal transduction and fluxes based on this concept.

You may find recent discovery of the insulin normalization/senstitization of FGF1 protein via intramuscular? injection (2014) and central (brain?) injection (2016) at 1/10 the concentration. to be even more significant for new perspective and insights into our understanding of Type2 diabetes and insulin resistance, provided we have sufficient surviving beta cells...

2014
One injection stops diabetes in its tracks
http://www.salk.edu/news-release/one-injection-stops-diabetes-in-its-tracks/

2016
Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents
http://www.nature.com/nm/journal/v22/n7/full/nm.4101.html

 

[Lamont D]

Hi Guys, I am starting this new thread because some of you out there were discussing already to move forward from the simple paradigm of muscle insulin resistance, liver insulin resistance and insufficient insulin production.

Here is a more sophisticated model: the eight causes of diabetes. I would like to ask people here, especially those who seem to have nailed down their management of blood glucose,

a. Have you identified which problems you have behind your high blood glucose?
b. If so, how did you did it?
c. What was the solution you used?

The eight causes, as explained by Dr DeFronzo in the lecture he gave when obtaining the 2008 Banting memorial prize are:

1. Muscle insulin resistance
2. liver insulin resistance
3. B cell disfunctiona first phase insulin secretion and insufficient insulin secretion
4. Fat cell accelerated lipolysis
5. incretin deficiency/resistance in the intestine
6. Hyperglucagonemia or disfunction of the alpha cells in the pancreas
7. increased glucose reabsortion in the kidney
8. Dysfunctional Brain messaging (for example insulin resistance)

Here are two links to overview the model.
A short video: https://www.novomedlink.com/profess...ous-octet-core-defects-in-type2-diabetes.html
The paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661582/

I just emailed to verify if he had major changes to this model from 2008. Will keep you posted.

I do not see hyperinsulinemia on that list and it is a major player driving insulin resistance and beta cell toxicity. Great list though and glad to not see fat and lazy on there.

All these seems to be symptoms rather than causes...

The "cause" would be what triggers the insulin resistance through the various system.
Liver, Muscles, Brain.

Is it the chronically elevated insulin levels triggered by high carbs/fructose diets?
Is it the other chemically induced endocrine disruptions that reduced FGF1 protein?

All of the above and in my case more.
The gut bacteria trigger to produce hormone imbalance which creates more insulin/glucose/ glycogen/glucagon, alpha and beta cells imbalance. Glucogenesis.
But the biggest problem facing doctors and the diabetes crisis is hyperinsulinaemia.