I Don't Understand Insulin Resistance...

[witan]

Of all the things I have had to learn about diabetes over the last couple of months the one that is still a mystery to me is Insulin Resistance.

The standard 'wrong key to unlock the energy in your cells' might be sufficient for pre-teens but is surely insulting and un-helpful to most adults of normal intelligence.

Has anyone on the forum got a better definition or links to somewhere that can describe how this happens and possible ways to reverse it?

 

[Trinkwasser]

Of all the things I have had to learn about diabetes over the last couple of months the one that is still a mystery to me is Insulin Resistance.

The standard 'wrong key to unlock the energy in your cells' might be sufficient for pre-teens but is surely insulting and un-helpful to most adults of normal intelligence.

Has anyone on the forum got a better definition or links to somewhere that can describe how this happens and possible ways to reverse it?

http://home.comcast.net/~fwroy/insulinresistance.html

WARNING: highly technical

 

[hanadr]

Dear witan
I thought you might find this interesting

The cause of the vast majority of cases of insulin resistance remains unknown. There is clearly an inherited component, as sharply increased rates of insulin resistance and Type 2 diabetes are found in those with close relatives who have developed Type 2 diabetes. However, there are some grounds for suspecting that insulin resistance is related to a high-carbohydrate diet. An American study has shown that glucosamine (often prescribed for joint problems) may cause insulin resistance.[6] Insulin resistance has also been linked to PCOS (polycystic ovary syndrome) as either causing it or being caused by it. Further studies are in progress. Other studies have also linked to the increased amounts of fructose (e.g., in HFCS — high fructose corn syrup, currently the least expensive nutritive sweetener available in industrial quantities), its fructose causing changes in blood lipid profiles, among other things. The high amounts of ordinary sucrose (i.e., table sugar) in the typical developed-world diet is also suspected of having some causative effect on the development of insulin resistance (sucrose is 1/2 fructose, which may account for the effect, if any). Insulin resistance has certainly risen in step with the increase in sugar consumption and the substantial commercial usage of HFCS since its introduction to the food trades.

 

[witan]

Wow that is quite a complex paper, but pulls together lots of studies -seems no one really knows the answer.

Diet - the usuall culprits - High CHO and fructose are sited
- an imbalance in the Calcium metabolism (dairy products?) and poor magnesium chemistry
- the effects of Free Fatty acids are also reviewed

Age - yes getting older doesn't help

Sleep - some interesting observations on how diabetics have the opposite daily insulin sensitivity to non-diabetics, diabetics are less sensitive in the morning more sensitive at night - this goes on to explain about the dawn phenomenom.

Of course the muscles are also key - so diet modification and excersise seem like the best options...

 

[Trinkwasser]

Yesterday someone dug up a paper I'd been looking for and couldn't find. It seems I hadn't downloaded it.

http://medicine.plosjournals.org/perlse ... ed.0020233

now I have!

 

[witan]

A good study but quite technical too.

This summary puts it nicely in a nut-shell...

Why Was This Study Done?

Children whose parents are diabetic have a higher risk of developing type 2 diabetes themselves. Some of them have the first signs of the disease (a condition called insulin resistance, which is a strong predictor for subsequent development of diabetes) while they are still young and lean. The group of Gerald Shulman (who is the senior author of this study) has studied such individuals to understand the causes and effects of their insulin resistance. Having previously found some abnormalities in the mitochondria (the parts of cells involved in generating energy), they studied mitochondrial function in more detail here.
What Did the Researchers Do and Find?

They compared seven young lean insulin-resistant adults with a family history of diabetes with seven lean young adults without diabetic family members and with normal insulin sensitivity. Specifically, they looked at energy generated in the muscles in response to insulin stimulation. They found that while insulin increases energy production in the muscles of the control individuals by approximately 90%, it had very little effect in the insulin-resistant individuals. They also studied the amount of inorganic phosphate (an essential trace element) in muscle cells of both groups, and how it was affected by insulin. They found that in control individuals, insulin results in an increase of phosphate transport into the muscle cells and that this is also much reduced in insulin-resistant individuals.
What Does This Mean?

Intracellular phosphate is a key regulator of energy generation, and this study provides more support for the notion that insulin resistance compromises proper functioning of energy generation in the mitochondria of muscle cells. This and similar studies should eventually result in a better understanding of the early events in diabetes. The hope is that this will then allow the development of therapies that might prevent the disease or treat its symptoms more effectively.
Shame all children and siblings of diabetics can't be tested for IR!

 

[Trinkwasser]

That was an interesting paper because it looked within the cells. A lot of the other stuff I've read concentrates on things like the GLUT-4 receptors which transport glucose *into* the cells (or not).

I have a belief that insulin resistance at the muscles and at the liver may also be quite separate events (when I say liver I include the rest of the control circuitry which includes the pancreatic alpha cells involved in producing glucagon to control the liver's glucose output). The system senses insulin levels rather than glucose levels in the blood and often fails to correctly recognise increased insulin as a signal to shut down the liver's output.

Then there's more work on insulin resistance within the brain, which may tie in to leptin and appetite.

Imagine a set of diabetic Russian dolls . . .