WHY DIABETES OCCURS ??..: From a simplistic... - Diabetes India

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WHY DIABETES OCCURS ??..

dharmendrapanchal profile image
โ€ข21 Replies

From a simplistic model of insulin deficiency and insulin resistance, researchers have moved to a multipronged explanation of the disease. In addition to the ominous octet, other eight players like catecholamines, vitamin D, reninโ€“angiotensin system, testosterone, melatonin, thyroid disorder, renal gluconeogenesis, gastrin - all play important roles in the etiology of glucose intolerance in type 2 diabetic individuals.

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dharmendrapanchal
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cure profile image
cureAdministrator

we can further read on same topic here

ncbi.nlm.nih.gov/pmc/articl...

dharmendrapanchal profile image
dharmendrapanchalโ€ข in reply tocure

thank you.. i have it.

cure profile image
cureAdministratorโ€ข in reply todharmendrapanchal

welcome sir...It is really nice to see atleast few doctors are trying to understand cause of diabetes...

Hope they will try to treat patients on these lines and not just beta cell squeezers..

dharmendrapanchal profile image
dharmendrapanchalโ€ข in reply tocure

please note only SU and GLINIDES are B cell squezzer

cure profile image
cureAdministratorโ€ข in reply todharmendrapanchal

However at the end of article... it is said...

' it has a high probability of achieving durable glycemic control. If the plasma glucose concentration can be maintained within the normal nondiabetic range, the microvascular complications of the disease, which are costly to treat and associated with major morbidity and mortality, can be prevented.'

here again they are worried about glycemic control...however the real problem is with excess insulin....even if some one remains in non diabetic range with excess insulin...he can not avoid other microvascular complications...

Activity2004 profile image
Activity2004Administratorโ€ข in reply tocure

Thank you, cure for the link. I will definitely check it out.

suramo profile image
suramoStarโ€ข in reply tocure

cure

I got another link and the questions i asked to the writer posting here.

1) In t2d insulin is not deficient. On the contrary it's high. But, if you continue same high carb diet, ir becomes so high that beta cells can't overcome that high ir and it's interpreted as beta failure.

2) Agreed.

3) Gluconeogenesis controlled by insulin! How? It's glucose which regulates neoglucogenesis. Could you please explain what regulates neoglu.... in type 1diabetes where insulin is absent? Or neoglu....doesn't occur in type 1?!!

4) In t2d lipolysis doesn't occur in presence of hyperinsulinemia. In t2d ketoacidosis is very rare to develop because presence of insulin prevents lipolysis and ketone overproduction. So I need to understand why high toxic levels of free fatty acids. The cause of muscle and liver ir is due to excessive lipogenesis which also gets deposited as visceral fat. If one wants to reverse D one has to lose abdominal / visceral fats completely or to a great extent.

5) "People with Type 2 diabetes often have an attenuated incretin response after meals." Please explain. Is it also because of "bad " genes? Any study showing attenuated incretin response after meals or mere postulation?

6) Are you talking about "liver dump "? Obviously in fasting state when glucose level go down not only glucagon but also many other hormones come into play but can they really cause diabetic levels of blood glucose? What about negative feed back? I don't think glucagon has any role in t2d and liver too is blind to insulin and not to glucose. Why should it engage in neoglu...despite very high bg levels?

7) Kidneys always absorb 100% glucose from urine. What do you mean by "In type 2 diabetes however, instead of dumping glucose into the urine, the kidney maladapts by reabsorbing more glucose instead". Isn't the statements self contradictory? On the contrary, glucose is passed in the urine as against no glucose in urine normally!

8) "Insulin has a very powerful appetite-suppressant effect, which is mediated by our brains. Unfortunately, this effect is lost as our brain tissues become resistant to insulin and can lead to obesity" ๐Ÿ˜๐Ÿ˜. Never knew insulin crosses bbb and brain needs insulin to utilize glucose.

Here is the article.

tengyan.me/ominous-octet-ho...

suramo profile image
suramoStarโ€ข in reply tosuramo

Anup

cure

dharmendrapanchal and everybody here. I have something more to say about the post.

9) Muscles and liver et become ir because of genetic defect. Naturally unhealthy gene expression is suppressed by healthy genes and over the next few generations such defective unhealthy genes are shed /lost by the nature. What makes D genes and the genes of familial hypercholesterolemia to continue over generations should be investigated.

10) Except glucagon, all the hormones like gh, acth, tsh etc. involved in gluconeo...are controlled by the brain through releasing hormones eg ghrh, acthrh etc. There is positive and negative feedback mechanism involved. Liver is not autonomous but has to obey the order of its master - the brain.

11) About the brain. I don't know what to say. Brain dependent on insulin for its glucose utilization!!๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’ Brain tissues become resistant to insulin. Anup we all would have become mentally retarded. Kya yar. Ye log kuchh bhi likhate hai oof. Aur hum log us baat ko maan k yaha bhejafry kar rahe hai!

All of a sudden our organs become our enemy and together form a cartel to kill us. Muze chakkar aa raha hai. cure bade bhaiya koi pani to pila do yaar.๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ™Š๐Ÿ™Š๐Ÿ™Š๐Ÿ™Š

โ€ข in reply tosuramo

I think pitutory gland is behind this phenomenon known as diabetes . All the other important organs like liver , speen , pancreas , heart etc are controlled by that gland . But no research has been done on the functioning of that gland fully

Activity2004 profile image
Activity2004Administrator

What about for type 1 diabetics, dharmendrapanchal ? Can this help a type 1, as well?

Anup, there is difference between etiology and pathophysiology of the disease.

Etiology is cause of the disease, which is high carb diet one of for diabetes.

Pathophysiology is mechanism by which disease developes. which are discussed above.

Hope you got the point

suramo profile image
suramoStar

Anup cure et al.

I'm still reading but there are many questions i'm gonna ask at the end of that article. I will post here later.

Activity2004 profile image
Activity2004Administratorโ€ข in reply tosuramo

Take your time, suramo . There's no rush.:-)

suramo profile image
suramoStar

Activity2004

Posting the article i have asked questions to to writer. For the benefit of the people here.

Back when I was in medical school, some 7+ years ago, diabetes mellitus didnโ€™t seem so complex. There were less big words โ€“ no canagliflozins, exenatides, sitagliptins, and the newest kid on the medication block were the T2Ds. And we were taught that there were 2 main mechanisms for the development of diabetes:

Insulin-resistance โ€“ your muscles and liver donโ€™t respond well to insulin.

Lack of insulin secretion โ€“ your beta-cells have lost their function.

Today, we know that there are at least 8 different mechanisms that play an important role in Type 2 diabetes โ€“ the โ€˜ ominous octet โ€˜. This was coined by Dr Ralph A. DeFronzo who delivered his Banting lecture on this topic (Dr Banting, by the way, was the good fella who first used insulin in humans). When I first came across the article, I was fascinated.

Ominious Octet

Who are the members of this โ€˜ominous octetโ€˜? Iโ€™ll explain it in layman terms that you can understand, even if you only know the basics of diabetes.

Letโ€™s start with the old fogeys.

1. Pancreatic Beta cells. (codename: THE FACTORY)

These are the good folks that produce all the insulin our bodies need to survive. When they start failing (perhaps from overwork), overall less insulin is available for our cells to use.

Grunts

2. Muscle cells (THE GRUNTS)

Our muscles are one of the largest utilisers of blood glucose in the body. Individuals who develop Type 2 diabetes inherit genes that make these tissues resistant to insulin.

When glucose is unable to enter the muscle cells, a lot of the glucose remains in the blood stream, especially after meals.

3. Liver (THE ALL-NIGHTER)

Our liver is the main player in glucose regulation when our bodies are in a fasting condition, such as during the night.

It produces glucose through a process called โ€˜gluconeogenesisโ€™ โ€“ this maintains your blood glucose levels at a constant, even if itโ€™s been a long time since your last meal. This process is regulated by insulin.

When the liver becomes resistant to insulin however, the liver keeps producing more glucose even when the blood glucose levels are already high.

4. Fat cells (THE BOUNCER)

Fat cells which are not functioning well will cause an elevation in free fatty acid levels. These result in โ€˜lipotoxicityโ€™, which overflows into muscle, liver and beta-cells causing insulin-resistance and reduced insulin secretion.

5. The gut (Gastrointestinal tract)

Although not typically acknowledged, our intestines are actually a major endocrine order. They secrete incretins (GLP-1 in particular), which are hormones that stimuate insulin and reduce glucagon secretion. People with Type 2 diabetes often have an attenuated incretin response after meals.

6. Pancreatic Alpha cells (THE REBEL)

Pancreatic alpha cells are the siblings of the the beta cells, and they produce glucagon, which is a hormone that is counter-regulatory to insulin. Itโ€™s been shown that increased levels of glucagon cause the liver to produce more glucose (through gluconeogenesis), resulting in higher fasting glucose levels.

7. Kidneys (THE SCAVENGER)

Our kidneys filter a good amount of glucose each day. In a normal individual, nearly 100% of the glucose is reabsorbed in the tubules, such that no glucose appears in the urine.

In type 2 diabetes however, instead of dumping glucose into the urine, the kidney maladapts by reabsorbing more glucose instead.

8. The brain (THE MASTERMIND)

Insulin has a very powerful appetite-suppressant effect, which is mediated by our brains. Unfortunately, this effect is lost as our brain tissues become resistant to insulin and can lead to obesity.

Now that we know there are multiple pathways that can cause high blood glucose levels in type 2 diabetes โ€“ effective treatment is no longer a single drug that targets one or two pathways. Effective treatment will target all of these pathways early in the disease, so as to prevent beta-cell failure.

Interestingly, sulphonylureas (a common class of diabetic medications) have been shown to reduce A1c and glucose levels โ€“ BUT have no protective effect on disease progression in the long run, unlike TZDs or GLP-1 agonists. Definitely something to think about.

cure profile image
cureAdministratorโ€ข in reply tosuramo

wow.... Wonderful explanation bhai suramo

HU is it possible to give 100 likes???

For me I always think about member no 3 Liver (THE ALL-NIGHTER) and member no 4 Fat cells (THE BOUNCER)

But sure they are all involved together.... but where it starts???

At liver?? at brain?? fats cells???beta cells??

a trigger point must be some where here....

cure profile image
cureAdministratorโ€ข in reply tocure

Bhai suramo may I request you to start a new thread on this and exapand it further???

may be more medical professionals would like to contribute in the discussion...

May be all our learned members like Hidden Hidden arunkumar shrisamarth jingale and of course anup at.el would like to contribute for the benefit of other members..

here is full article

diabetes.diabetesjournals.o...

suramo profile image
suramoStarโ€ข in reply tocure

cure

If you are talking about the article i'm sorry i don't agree. I have to disappoint you. A simple cause and simple pathophysiology is complicated by multiple theories and no proof. Sometimes i feel these people get lots of money from ๐Ÿ’๐Ÿ’๐Ÿ’ sources for research ๐Ÿ’๐Ÿ’๐Ÿ’๐Ÿ’. we all know what the remedy is. Such theories are nothing but fumbling in darkness. They will now come up with new medication!!๐Ÿ’๐Ÿ’๐Ÿ’. Adding to the present Illogical medications. Sorry dharmendrapanchal for using such words. Why do we seek cure in medicines only? Weird.

cure profile image
cureAdministratorโ€ข in reply tosuramo

Bhai suramo what I mean is that yes...For D there many reasons...

This will open up the more discussion... this is something different thought for standard medical practice...

Many who wish to update themselves would like to discuss and learnโ€ฆ

suramo profile image
suramoStar

dharmendrapanchal

I need to understand a lot about this ominous octet theory but the progression of t2d stops when we stop taking carbs. Thousands of years ago when the grains / carbohydrates were not invented humans lived without carbs. So carbs as a fuel may be good because of its universality, abundance and cheapness but not inevitable.

suramo profile image
suramoStar

Anup

dharmendrapanchal

I'm surprised by this theory. Why should we get carried away by such postulations?

Liver, kidney and brain are not responsible for t2d. They are the victims.

My understanding is as follows. Due to some reason not known to us, but probably a genetic defect gradually our body stops /can't utilise glucose efficiently. There Is hyperglycemia. High sugar in tissues cause osmotic damage. Now putting weird theories! I find no facts in this theory. Theory without evidence.

Once we lose fat esp abdominal our ir abates and at least we are saved from the deleterious effects of hypergl....only genetic theory can explain why our whole body gradually fails to utilize glucose effectively. The defect remains lifelong and unless we change our lifestyles D is not going to reverse.

cure profile image
cureAdministrator

Dear Hidden plz go thru entire thread....

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