New method of treating type 1 diabetes proposed by US researcher

[DCUK NewsBot]

Targeting the liver with insulin could be the best way to treat type 1 diabetes, US researchers have claimed. A team from the Vanderbilt University Medical Center set out to investigate whether people with type 1 diabetes experience resistance to the manufactured insulin they take and consider how insulin delivery may affect the risk of complications. To date, it is widely believed that high levels of glucose leads to greater risk of diabetes-related complications, but lead researcher Dr Justin Gregory, who was diagnosed with type 1 diabetes more than 19 years ago, does not agree. The assistant professor of Pediatrics at the medical centre said: "There's more to treating type 1 diabetes than just bringing down high blood sugar." He thought the answer might have more to do with the way insulin is delivered into muscle. In people who do not have diabetes, insulin is produced by the pancreas first before it travels via the liver, halving the amount of the hormone before it is despatched to the muscle. However, when insulin is injected under the skin in those with diabetes, a key part of that process is bypassed, and the liver is initially missed. Dr Gregory said that injecting insulin under the skin meant he had "too much insulin at muscle and not enough at liver—all because I'm putting insulin in the wrong place". "Restoring that balance is important toward helping people with type 1 diabetes reduce their risk of heart disease," he added. Dr Gregory's theory with regard to heart disease risk is based on association between insulin resistance and inflammation. To prove the theory that people with type 1 diabetes have resistance to the insulin they take, the team carried out tests on people with type 1 diabetes and compared the results with people with a different form of diabetes, known as GCK-MODY. People with GCK-MODY have a genetic condition, affecting the GCK (glucokinase) gene, that affects the pancreas’ sensing of how high blood glucose levels are. This leads to people with GCK-MODY having higher than normal blood glucose levels. By choosing people with GCK-MODY as a comparison group, the team were able to compare differences in tests with two groups that both had similarly high blood glucose levels. Both groups had their blood glucose adjusted to the same level, then their insulin levels were compared. The MODY group's insulin levels were deemed in the healthy range, whereas insulin levels among those with type 1 were 2.5 times higher. Dr Gregory said his study "brings to light the need to develop therapeutic strategies to keep the appropriate balance of insulin between the liver and peripheral insulin-sensitive tissues". He added: "We need to come up with ways of delivering insulin that replicate that normal balance of insulin." The findings have been published in the journal Diabetes.

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[JAT1]

Thanks for the fascinating article !

 

[KK123]

Wow, fascinating. As long as it doesn't involve a needle straight into the liver! Ouch.

 

[Scott-C]

Wow, fascinating. As long as it doesn't involve a needle straight into the liver! Ouch.

Well, that's one way, I suppose!

For a while now, Diasome has been working on hepatic directed vesicles, a compound which gets added to normal insulin, and by some miracle of chemistry, takes some of the insulin straight to the liver, so that the liver will do what it is supposed to and buffer incoming carbs before they get into the bloodstream.

Haven't followed their progress for a while, but a recent June 2019 press release says they've recently finished enrolling patients for a 3 month trial, so watch this space.

This could make a big difference if it works..

https://www.diasome.com/

http://www.globenewswire.com/news-r...ed-Vesicle-Technology-in-Type-1-Diabetes.html

 

[LittleGreyCat]

It is a bit "This is the problem. It is now your job to find the solution."

The first thing I would like to know is how insulin initially travels from the pancreas to the liver.
It is transferred via the blood stream, but does it go via a blood vessel directly to the liver before being released to the rest of the body?
I've searched for this but not found an answer so far.

Hmmm...hepatic portal vein was in the back of my mind and this does seem to carry blood directly from the internal organs including the pancreas to the liver. [As implied by the name.]
Easy if you guess the answer and work back to the question.

I can visualise that subcutaneous insulin injections are likely to send the insulin directly to all parts of the body, which in turn implies that much/most of the insulin may never get as far as the liver.

This in turn implies that you might in future be looking at some kind of "shunt" which inserts insulin into the blood stream into a vessel that carries a flow from the pancreas to the liver.

This would be much closer to an artificial pancreas.

This would also have major implications for insulin dosing. No more long acting basal, for example. Any insulin released would be in the liver in seconds.

Interesting stuff.

 

[ringi]

The first thing I would like to know is how insulin initially travels from the pancreas to the liver.
It is transferred via the blood stream, but does it go via a blood vessel directly to the liver before being released to the rest of the body

This blood vessel is easy to access in dogs, but very hard to access in people. Hence so much research is done in dogs.

The pancreas also gets the blood directly from the digestive system, hence can sence BG before it gets to rest of the body. So can preemptively release inslin to the liver when BG is about to increase. There are additional messaging systems from the digestive system to the pancreas, these are not yet well understood.

At times of rapid increasing BG, the inslin concentration in the liver is many times higher then the rest of the body. This happens when carbs are eaten. The liver then stops releasing glocose and starts taking up glocose from the blood.

In type2 the liver does not correctly respond to this high concentration of inslin, in type1 there is no way to direct a high concentration of inslin at the liver.

When people without diabetes eats a very low carb meal the inslin concentration is much the same over the complete body and the liver does much less.

 

[Robinredbreast]

Wow, fascinating. As long as it doesn't involve a needle straight into the liver! Ouch.

How would we as the patient, inject into the correct area ? I had elevated Liver when pregnant, HELLP syndrome and it was very painful.
Probably someone else will say the complete opposite and the idea/research will go on and on and on, don't think it will happen in my lifetime though.

 

[LittleGreyCat]

How would we as the patient, inject into the correct area ? I had elevated Liver when pregnant, HELLP syndrome and it was very painful.
Probably someone else will say the complete opposite and the idea/research will go on and on and on, don't think it will happen in my lifetime though.

Couldn't work like that as far as I can see.
Certainly not probing about trying to hit a major blood vessel with a needle on a regular basis.

There would have to be an artificial connection into (probably) the hepatic portal vein which allowed both monitoring of BG and a metered amount of insulin being added to the blood.

Very much an automated system.

 

[Scott-C]

How would we as the patient, inject into the correct area ?

Diasome are trialling an additive to insulin called "hepatic directed vesicles" the idea being you'd inject as normal and the hdv takes the insulin to the liver.

https://www.diasome.com/

http://www.globenewswire.com/news-r...ed-Vesicle-Technology-in-Type-1-Diabetes.html

 

[Robinredbreast]

Diasome are trialling an additive to insulin called "hepatic directed vesicles" the idea being you'd inject as normal and the hdv takes the insulin to the liver.

https://www.diasome.com/

http://www.globenewswire.com/news-r...ed-Vesicle-Technology-in-Type-1-Diabetes.html

Thanks Scott

 

[Robinredbreast]

Couldn't work like that as far as I can see.
Certainly not probing about trying to hit a major blood vessel with a needle on a regular basis.

There would have to be an artificial connection into (probably) the hepatic portal vein which allowed both monitoring of BG and a metered amount of insulin being added to the blood.

Very much an automated system.

I shall await with anticipation