Questions about Diabetes?

[Kumar]

Being dogmatic about your own theories regarding this just doesn't fit. In fact I am not even sure what they are. But insofar
as your claim that giving a larger dose is not the same as giving a higher concentration (of insulin or any drug) is just wrong from the receiving organism's side. As anybody knows, if you are required to take say 50 mgs of a drug and only have 25 mg tablets, then taking two of them is precisely equivalent to taking one 50 mg dose. If you need 200 units of insulin but only have 100 unit/ml insulin then taking two mls works.

Prescribing 50mg instead 25 mg may mean that 25mg is not sufficient. If we give half cup of milk to a hungry person who need more milk & then give half more, it means full cup milk is utilized but if we give to a person already overtaken, extra milk may mean problem not utilization. I just see that insulin level should be exactly balanced neither less nor more as both may create high BG level one by its deficiency & other buy its defficiency due to non-utilization.

High insulin levels accompanying high glucose levels in an IR individual requires then either higher levels, a different type of insulin, or insulin in combination with oral A-D agents as well as tweaking of diet.

All these things may work only when insulin level in blood is exactly balanced, neither excess nor low.

Furthur, i don't understand how a diabetic person can experiance hypoglycemia shots when he take excess oral dose or injected insulin inspite of fact whole body glucose is same & moreover that is getting utilized with more insulin as per the current theory.

 

[Dr. Imago]

Prescribing 50mg instead 25 mg may mean that 25mg is not sufficient. If we give half cup of milk to a hungry person who need more milk & then give half more, it means full cup milk is utilized but if we give to a person already overtaken, extra milk may mean problem not utilization. I just see that insulin level should be exactly balanced neither less nor more as both may create high BG level one by its deficiency & other buy its defficiency due to non-utilization.

You are applying a simplistic, anecdotal logic to a topic you do not understand: non-linear pharmacokinetics. Likewise, you have to understand receptor saturation and ligand theory, which you also do not.

-TT

 

[Kumar]

You are applying a simplistic, anecdotal logic to a topic you do not understand: non-linear pharmacokinetics. Likewise, you have to understand receptor saturation and ligand theory, which you also do not.

-TT

TT, I usually finds that common & simple logics hold some meaning in most of the aspects. However, will you explain: how additional insulin given to a patient with IR who already have excess insulin in blood, can be effective?

Can a patient with IR experiance hypoglycemea type shots due to increase in IR condition ( non-taking of energy by cells) by taking excess & additional insulin or more sugar(whichever is responsible for IR)? Whether hypoglycemia effect is due to excess insulin, low glucose in blood(common consideration) OR due to insulin/glucose not effective to the cells due ti IR?

 

[materia3]

TT is correct. You cannot compare this with drinking more or less milk to quench thirst or trying to dissolve a stone with "more" water. Neither are relevant. It is simplistic, anecdotal in the extreme and has no bearing on what is truly taking place.

Perhaps the following definition of insulin receptor will help you to
appreciate that the "conventional wisdom" to which you cling cannot be applied in this example:

A cell surface receptor for INSULIN. ... is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precusor protein. The receptor contains an intrinsic tyrosine kinase domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the LIVER; MUSCLE; and ADIPOSE TISSUE.

http://fred.hmc.psu.edu/ds/retrieve/fred/meshdescriptor/D011972

In your call for balancing: you also persistently ignore the importance or even recognition of the existence of self-testing in balancing carbohydrate (sugar) and insulin loads. This is the avowed purpose of self-testing; doing so sucessfully is evidenced by the outcome of the testing.

 

[Kumar]

materia3,
"Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the LIVER; MUSCLE; and ADIPOSE TISSUE."

Suppose I say that this activation is unabled either as an indigetion/overload type effect of insulin or dawn receptors problem then??

Just read it-

Dr. Weyer and colleagues conducted a longitudinal study on 48 adult Pima Indians--a group considered at high risk for developing both diabetes and obesity. At study entry, all participants had normal glucose tolerance. Each year, the investigators measured body composition, glucose tolerance, insulin action, oxidative versus nonoxidative disposal of glucose, insulin secretory capacity, and endogenous glucose production rate in each subject.

Over the course of the study 17 persons progressed from normal glucose tolerance to impaired glucose tolerance, then to diabetes; these were called "progressors." The remaining 31 subjects continued to have normal glucose tolerance ("non-progressors"). In a comparison of the two groups, the investigators found that

* Progressors gained more weight (both fat and lean mass) than did non-progressors;

* Fasting insulin levels increased steadily as subjects progressed from normal glucose tolerance to diabetes--suggesting that insulin secretion becomes progressively abnormal as insulin resistance increases; and

* Progressors were ultimately unable to compensate for increased insulin resistance by increasing their insulin output; however, non-progressors did increase insulin output. These findings support previous studies concluding that diabetes results from diminished early insulin secretion plus defects in the patient's ability to respond to insulin.

Persons at high risk for this steady downslide into type 2 diabetes might benefit from aggressive preventive measures, including diet and weight loss--but identifying such individuals has been difficult. The usual research methods for measuring insulin resistance and insulin secretory ability are not usable in routine clinical practice. However, Dr. Marian Rewers reported that the oral glucose tolerance test, combined with fasting and 2-hour insulin levels, is almost as accurate for predicting diabetes risk as research tools that are extremely sensitive but clinically impractical.

In the Insulin Resistance and Atherosclerosis Study, Dr. Rewers and colleagues conducted a statistical analysis comparing the power of easily measured clinical parameters, such as body mass index and fasting blood glucose, to the results of oral glucose tolerance tests and rapid-sampling intravenous glucose tolerance test (IVGTT) in 1,500 subjects at different stages of glucose tolerance. They found that IVGTT was, as expected, the most reliable at predicting future development of type 2 diabetes--but that oral glucose tolerance testing and fasting blood glucose values were only slightly less accurate.

STEPS IN DEVELOPMENT OF TYPE 2 DIABETES

1. Normal glucose tolerance

2. Defects in glucose synthesis and storage; development of insulin insensitivity

3. Increase in fasting insulin levels

4. Pancreatic [beta]-cell dysfunction, leading to defective insulin secretion

5. Defects in suppression of endogenous glucose production (insulin resistance in the liver)

Actually, insulin & glucose load to target cells is at the same time. How can you judge by self testing of insulin & BG levels that which of these is causing IR. The above quote also indicate Fasting insulin levels increased steadily as subjects progressed from normal glucose tolerance to diabetes--suggesting that insulin secretion becomes progressively abnormal as insulin resistance increases.

It can be better to compare other hormones & related biochemicals to those. How cells behave in those cases? Do they become resistant to that hormone or to related biochemicals?

Furthur I want to study more on 'Emerging Patterns Of Diabetes Progression'. Can you provide some details/links?

 

[Dr. Imago]

TT, I usually finds that common & simple logics hold some meaning in most of the aspects.

Well, you'd be wrong and this is a common error laypeople make.

However, will you explain: how additional insulin given to a patient with IR who already have excess insulin in blood, can be effective?

No, I won't. This has already been explained to you. I suggest, if you want more info, you do a web search.

-TT

 

[Dr. Imago]

It can be better to compare other hormones & related biochemicals to those. How cells behave in those cases? Do they become resistant to that hormone or to related biochemicals?

Kumar, two words: receptor regulation.

Look it up.

-TT

 

[Kumar]

Kumar, two words: receptor regulation.

Look it up.

-TT

It it not correct that receptor regulation is controlled by hormones or exposure of hormones to cells?

Hormone receptor regulationReceptor regulation is an important part of endocrine function and this occurs through up or down-regulation of the number of receptors and by desensitization of the receptors. This occurs by increasing or decreasing receptor synthesis, by internalization of membrane receptors after ligand binding, or by uncoupling of the receptor from its signal transduction pathway (desensitization). The latter usually involves phosphorylation of the receptor. Some hormones may regulate their own receptors (homologous regulation) such as GnRH on the pituitary gonadotrophs whilst other receptors are regulated by other hormones (heterologous regulation) e.g. estrogen regulating oxytocin receptors.

Interaction between hormones and their receptors depends on the number of receptors, the concentration of circulating hormone and the affinity of the hormone for the receptor. The latter is defined as the concentration of a hormone at which half the total number of receptors is occupied (Box 1.14) and the higher the affinity the lower the concentration of hormone required. Generally speaking the affinity of hormone receptors does not change and thus the biological response depends on the number of receptors and the concentration of hormone.

Usually less than 5% of hormone receptors are occupied at any one time and maximum biological responses are achieved when only a fraction of the total number of receptors are occupied. Thus, it might be questioned why a small reduction in receptor number or a change in hormone concentration should make much difference to the overall biological response. This is governed by the law of mass action. If receptor numbers are reduced then the chances of a hormone binding to a receptor are decreased. Thus, a higher concentration of hormone is required to achieve a similar receptor occupancy. A similar argument may be applied when hormone concentrations are reduced. Together these two parameters are important in determining the target cell's response to a hormone despite low occupancy of receptors.

Can't it be possible that numbers of hormone receptors are reduced when hormone/insulin concetration is increased?

 

[Dr. Imago]

It it not correct that receptor regulation is controlled by hormones or exposure of hormones to cells?

Did you look it up? Read, Kumar, read. Try to understand first. Stop asking so many questions that you really don't want to know the most correct and scientifically agreed upon answers to nor are willing to accept.

-TT

 

[Kumar]

Did you look it up? Read, Kumar, read. Try to understand first. Stop asking so many questions that you really don't want to know the most correct and scientifically agreed upon answers to nor are willing to accept.

-TT

Pls read my previous post again as i editted.

 

[Badly Shaved Monkey]

Can't it be possible that numbers of hormone receptors are reduced when hormone/insulin concetration is increased?

and...?

 

[Kumar]

With insulin, however, the rate of glucose entry is much increased due facilitated diffusion as mediated by transporters.


The insulin-receptor complex enters the lysosomes where it is cleaved, the hormone internalized and the receptor recycled. Increased circulating levels of insulin reduce the number of receptors--down-regulation of receptors--and decreased insulin levels increase -- up-regulation--the number of receptors. The number of receptors per cell is increased in starvation and decreased in obesity and acromegaly; receptor affinity is decreased by excess glucocorticoids.
http://mcb.berkeley.edu/courses/mcb135e/pancreas.html

What does it mean?

 

[Kumar]

Hello,

How can we relate level of cholesterols in blood with the imbalances in blood glucose in view of 'Synthesis of the various hormones from cholesterol'? Can low level of cholesterol lead to high blood sugar or uncontrolled & persistant high BG?

 

[Badly Shaved Monkey]

What does it mean?

It means what it says.

http://web.indstate.edu/thcme/mwking/diabetes.html

http://www.postgradmed.com/issues/2004/07_04/sivitz.htm

http://www.emedicine.com/med/topic1173.htm

"Except in a few rare cases involving antibodies to the insulin receptor or mutations in the insulin receptor gene, the insulin resistance of diabetes results from impairments in cellular events distal to the interaction between insulin and its surface receptor"

 

[Dr. Imago]

It means what it says.

You gotta admire his tenacity.

-TT

 

[Kumar]

It means what it says.

http://web.indstate.edu/thcme/mwking/diabetes.html

http://www.postgradmed.com/issues/2004/07_04/sivitz.htm

http://www.emedicine.com/med/topic1173.htm

"Except in a few rare cases involving antibodies to the insulin receptor or mutations in the insulin receptor gene, the insulin resistance of diabetes results from impairments in cellular events distal to the interaction between insulin and its surface receptor"

BSM,

In view of above, we can also think of excess insulin may trigger the insulin resistance of diabetes results from impairments in cellular events distal to the interaction between insulin and its surface receptor"

Fat distribution, as opposed to total body fat, may be a critical factor, because insulin resistance is now well known to be associated with intra-abdominal fat (15,16). This association may be due to increased delivery of fat directly to the liver through the portal circulation.

It also appears that IR starts after sugar-fats coversion phase is also at optimum level or when insulin also become resistant to glucose-fat conversion.

Of interest, the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) may be up-regulated in obesity (17). The enzyme generates active cortisol from inactive cortisone and is expressed to a greater extent in omental fat than in subcutaneous fat. It has been hypothesized that this process results in a type of localized Cushing's syndrome, which potentially encourages central adiposity and insulin resistance. Thus, it is possible that inhibitors of 11-beta-HSD1 may be effective for treating insulin resistance.(from 2nd link above)

It may be important to understand cholesterol>>cortisol role in glucose metabolism.

It is interesting:-

Main clinical implications of insulin resistance
Insulin resistance is strongly associated with the other features of metabolic syndrome.



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It remains unclear whether insulin resistance is a primary cause of vascular disease or other aspects of metabolic syndrome.



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The potential causes of insulin resistance are diverse. Different causes may eventually prove to have different clinical implications.



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Insulin resistance can be quantified in research studies, but the methods are complex and not suited to individual patients in the clinical setting.



--------------------------------------------------------------------------------

Improving insulin resistance with diet, exercise, or pharmacologic insulin sensitizers generally improves other aspects of metabolic syndrome.



--------------------------------------------------------------------------------

The indications for treating insulin resistance with pharmacologic insulin sensitizers in the absence of hyperglycemia are still evolving.
(from last link above)

 

[MRC_Hans]

In view of above, we can also think of excess insulin may trigger the insulin resistance of diabetes results from impairments in cellular events distal to the interaction between insulin and its surface receptor"

No, because excess insulin does not happen before insulin resistance developes. The fact that A comes after B may not mean that A causes B, but it does mean that B does not cause A.

Excess insulin will immidiately lead to a hypogluchaemic episode, unless there is insulin resistance.


It also appears that IR starts after sugar-fats coversion phase is also at optimum level or when insulin also become resistant to glucose-fat conversion.

Insulin does not become resistant to anything.


It may be important to understand cholesterol>>cortisol role in glucose metabolism.

It certainly is, but I'm afraid you have a long way to go before you can understand such complex issues.

It is interesting:-

Very. And very very complex.

Hans

 

[Kumar]

No, because excess insulin does not happen before insulin resistance developes. The fact that A comes after B may not mean that A causes B, but it does mean that B does not cause A.

Excess insulin will immidiately lead to a hypogluchaemic episode, unless there is insulin resistance.

No, there can be prediabetic IR due to ocassional & excess insulin secretions by abnormal eating habits(genetically predisposed or due to modern lifestyle/environment). Medications may add to it if insulin can be a cause.

 

[MRC_Hans]

No, there can be prediabetic IR due to ocassional & excess insulin secretions by abnormal eating habits(genetically predisposed or due to modern lifestyle/environment). Medications may add to it if insulin can be a cause.

There can be a prediabetic IR, if you define that as an IR that does not cause raised BG, but it cannot be due to excess insulin because that would cause hypo episodes.

You have to distinguish between a high insulin production and excess insulin. If a normal person eats a lot of sugar, he/she will produce a large amount of insulin in order to metabolize it, but that is not an excess amount of insulin, that is the necessary amount.

To my knowledge, an excess consumption of sugar has not been observed to lead to diabetes, except through overweight (which is an indirect effect).

It is possible for a healthy person to produce excess insulin; for instance if you eat a lot of sweets in a short time, then rest for about half an hour (in which time a lot of insulin will have been released to deal with the glucose), then exercise vigorously. You will then burn off so much of the glucose that the released insulin will be too much and you will experience a (relatively mild) hypo. But that is a special situation.

How did you get the idea that excess insulin can lead to IR and why do you want it so badly to be true?

Hans

 

[Kumar]

There can be a prediabetic IR, if you define that as an IR that does not cause raised BG, but it cannot be due to excess insulin because that would cause hypo episodes.

"The body manufactures insulin to transport sugar (glucose) into cells so they can use it for energy. Obesity worsens insulin resistance, making it increasingly difficult for cells to respond to insulin. The body reacts by releasing more insulin to "override" the insulin resistance."

Hypo shots may be after when insulin & glucose can be fully used by cells & then no furthur glucose is available. I am not sure whether hypo shot can also be experianced as glucose not used due to IR/Over IR condition? Anyway in IR condition both BG & insulin can be excessive, still hypo shots are not experianced. I think hypo shots can also be dependant on 'how cells are able to take sugar other than how much sugar in available'.

You have to distinguish between a high insulin production and excess insulin. If a normal person eats a lot of sugar, he/she will produce a large amount of insulin in order to metabolize it, but that is not an excess amount of insulin, that is the necessary amount.

I think in IR excess insulin as well as excess glucose is there. Occasional Exposure of insulin in large amount to cells can make them bored and unwilling to take more glocose & insulin effect. If we eat more & iregularily, the digestive secretions can be said to be necessary but still imbalanced/excessive & so can cause progressive damages.

To my knowledge, an excess consumption of sugar has not been observed to lead to diabetes, except through overweight (which is an indirect effect).

It may depend upon predisposition of a person/constitution.

It is possible for a healthy person to produce excess insulin; for instance if you eat a lot of sweets in a short time, then rest for about half an hour (in which time a lot of insulin will have been released to deal with the glucose), then exercise vigorously. You will then burn off so much of the glucose that the released insulin will be too much and you will experience a (relatively mild) hypo. But that is a special situation.

That is common understanding.

How did you get the idea that excess insulin can lead to IR and why do you want it so badly to be true?

My observations & logics indicate this concept accordingly. Moreover, real /basic cause to IR is not yet known. ALSO by reducing or discontinuing of medications are also not yet been clinically tried.