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Type 2 First phase insulin, Metformin & GLP-1

finsit

Well-Known Member
I have a question about first phase insulin response which i will breakdown into two sub questions.

1. Has anyone who has no insulin resistance, not obese, low BMI, no belly fat has seen significant decrease in postprandial blood glucose with Metformin ? Means does Metformin helps in activating insulin secretion signals or affects GLP-1?

2. Was anyone able to improve their first phase insulin increase and if so how? I saw a paper that says l glutamine increases GLP-1 and hence helps in insulin release signals.


Thanks
 
Most readers of your post will have no idea if they have insulin resistance. It is not measured by standard tests. Secondly, my understanding of what Metformin does is that it can help reduce IR in muscle tissue. Metformin does not activate insulin production. it does reduce the glucose released by the liver and I suppose this could affect the timing of the first response which is glucose step level sensitive. Remember that the first phase insulin response is the release of stored insulin from the granules in the beta cells which were charged up slowly over time prior to your meal so it is more like a dam bursting i.e. a short high spike some 10 minutes after first bite and lasting about 10 to 15 minutes only. Because it is so short, it is difficult to measure even on a CGM. Normally an oral stimulus will not trigger much of a Stage #1 response, and it is normally only visible when the stimulus is intravenous such as in the insulin clamp IVGTT test.

The booster that increases the insulin output is sulfonylurea as produced by the delta cells or by a medication such as gliclazide. Boosting GLP-1 will generally increase the time the demand signal for the insulin production is active as shown by meds such as the Glutides. These prolong the second phase insulin response.

However, if you have significant insulin resistance then boosting output is not going to gain much., i found that reducing my iR was more efficient than dosing up on meds to thrash my poor pancreas.
 
Most readers of your post will have no idea if they have insulin resistance. It is not measured by standard tests. Secondly, my understanding of what Metformin does is that it can help reduce IR in muscle tissue. Metformin does not activate insulin production. it does reduce the glucose released by the liver and I suppose this could affect the timing of the first response which is glucose step level sensitive. Remember that the first phase insulin response is the release of stored insulin from the granules in the beta cells which were charged up slowly over time prior to your meal so it is more like a dam bursting i.e. a short high spike some 10 minutes after first bite and lasting about 10 to 15 minutes only. Because it is so short, it is difficult to measure even on a CGM. Normally an oral stimulus will not trigger much of a Stage #1 response, and it is normally only visible when the stimulus is intravenous such as in the insulin clamp IVGTT test.

The booster that increases the insulin output is sulfonylurea as produced by the delta cells or by a medication such as gliclazide. Boosting GLP-1 will generally increase the time the demand signal for the insulin production is active as shown by meds such as the Glutides. These prolong the second phase insulin response.

However, if you have significant insulin resistance then boosting output is not going to gain much., i found that reducing my iR was more efficient than dosing up on meds to thrash my poor pancreas.
Thanks for your detailed response. There is so much in insulin signalling that is still not discovered. You could have stored insulin granules, but sometimes first phase trigger is lacking for whatever reason, hormonal/incretin etc. So what i have noticed is that insulin gets a nudge at a certain BG level and then it performs well, which makes me doubt that its more of signalling issue than production. So much is being discovered about Metformin as well so just wanted to see if anyone has personal experience of controlling postprandial in the absence of IR (anyone who understand it or keeps an eye on this). My BG could stay in 6-7 mmol for prolonged time in the absence of this insulin nudge. However, if i eat some sugar with a meal, it will take a quick spike but then will go down to 5, which makes me suspect there is some insulin signalling issue or there is a threshold.
 
My BG could stay in 6-7 mmol for prolonged time in the absence of this insulin nudge. However, if i eat some sugar with a meal, it will take a quick spike but then will go down to 5,
Maybe your body is quite happy at 6-7 and only needs to act when you force it higher by eating sugar?
 
Maybe your body is quite happy at 6-7 and only needs to act when you force it higher by eating sugar?
If i know that for certain, i am more than happy to live my life, but what science says is that your optimal oxidative stress, AGEs creation is about 5.5 mmol, anything above that is definitely going to cause extra burden on your mitochondria.
 
I'm confused. I naively thought IR was pretty well the definition of T2 diabetes, well IR leading to too high bgs? Are there T2s out there who don't have insulin resistance?
I checked and i know i dont have. My HOMA-IR is 0.68. I definitely used to have before diagnosis.
 
If i know that for certain, i am more than happy to live my life, but what science says is that your optimal oxidative stress, AGEs creation is about 5.5 mmol, anything above that is definitely going to cause extra burden on your mitochondria.
5.5mmol/l is a normal non diabetic blood sugar level, everyone diabetic or not will at some point measure above 5.5.
Especially with the current accuracy limitations of home testing kit, looks like we're all doomed. :nailbiting:
 
I have a question about first phase insulin response which i will breakdown into two sub questions.

1. Has anyone who has no insulin resistance, not obese, low BMI, no belly fat has seen significant decrease in postprandial blood glucose with Metformin ? Means does Metformin helps in activating insulin secretion signals or affects GLP-1?

2. Was anyone able to improve their first phase insulin increase and if so how? I saw a paper that says l glutamine increases GLP-1 and hence helps in insulin release signals.


Thanks
1. I'm not a practitioner, so without significant proof of someone has posted it on here, I would say no! Because as others have posted.
Metformin does not work that way. If it did, you would not need any other meds!

2. There are drugs out there that do that!
In my experience with poor first phase insulin response. I have improved my health by not allowing my blood glucose levels to go above normal levels (ish) This does seem to reduce IR over time.
There is more to things that most endocrinologists are still trying to work out, to prove, how is the response triggered, is it by the senses to food and how much does each hormone secrete, how is it controlled?
the stomach, the gut bacteria, the intestines, the organs, the glands, the cells, and most importantly the brain itself. Even how your brain functions such as stress, anxiety, and so on, even epilepsy, Alzheimer's have seen improvement when certain foods could trigger an episode.
And then we are all individual and our environment is so different from each other!

Trying to understand the intricacy of our bodies, there are so many questions and not enough answers.
Why is wheat written in bold letters on food products?
What are they not telling us with bleached foods?
And why don't the doctors test for insulin levels as well as hba1c levels?
Why are they using processed foods full of ingredients that are known to cause issues?
Why do GP's resort to medication before investigating the cause?
Why aren't GP's trained better in the many differences in diabetes?
And for myself, why doesn't most doctors know about my condition?

And more.
 
If i know that for certain, i am more than happy to live my life, but what science says is that your optimal oxidative stress, AGEs creation is about 5.5 mmol, anything above that is definitely going to cause extra burden on your mitochondria.
Is it possible that a good quality of life is possible without the perfection you seem to perpetually seek? I’d so fear you are missing out on life by continua seeking the holy grail.
 
What is "first phase insulin response", how many phases are there and why are the phases relevant rather than just asking about "insulin response"?

I have not nly recently seen this "first phase insulin response" phrase mentioned and not with any explanation of what it means
I have tried Google but nonthewiser why it is asked here
 
Trying to understand the intricacy of our bodies, there are so many questions and not enough answers.
Why is wheat written in bold letters on food products?
What are they not telling us with bleached foods?
And why don't the doctors test for insulin levels as well as hba1c levels?
Why are they using processed foods full of ingredients that are known to cause issues?
Why do GP's resort to medication before investigating the cause?
Why aren't GP's trained better in the many differences in diabetes?
And for myself, why doesn't most doctors know about my condition?

And more.
I can answer one of those: because it’s a known allergen!
 
1. I'm not a practitioner, so without significant proof of someone has posted it on here, I would say no! Because as others have posted.
Metformin does not work that way. If it did, you would not need any other meds!

2. There are drugs out there that do that!
In my experience with poor first phase insulin response. I have improved my health by not allowing my blood glucose levels to go above normal levels (ish) This does seem to reduce IR over time.
There is more to things that most endocrinologists are still trying to work out, to prove, how is the response triggered, is it by the senses to food and how much does each hormone secrete, how is it controlled?
the stomach, the gut bacteria, the intestines, the organs, the glands, the cells, and most importantly the brain itself. Even how your brain functions such as stress, anxiety, and so on, even epilepsy, Alzheimer's have seen improvement when certain foods could trigger an episode.
And then we are all individual and our environment is so different from each other!

Trying to understand the intricacy of our bodies, there are so many questions and not enough answers.
Why is wheat written in bold letters on food products?
What are they not telling us with bleached foods?
And why don't the doctors test for insulin levels as well as hba1c levels?
Why are they using processed foods full of ingredients that are known to cause issues?
Why do GP's resort to medication before investigating the cause?
Why aren't GP's trained better in the many differences in diabetes?
And for myself, why doesn't most doctors know about my condition?

And more.
I am with you on this 100%. Been gone through this roller coaster and then enrolling into a full time nutrition degree, I just realised doctors are not helping out at least T2 as well as they should and then pharma influenced carb rich diet that regulatory bodies force onto medical system doesn't make sense either plus all other things you mentioned. I am on a journey of finding at least my personal condition to understand it better.
 
Is it possible that a good quality of life is possible without the perfection you seem to perpetually seek? I’d so fear you are missing out on life by continua seeking the holy grail.
That's what my goal is for now hence these questions to set up a path that works for me at least and live a more un- paranoid life :)
 
What is "first phase insulin response", how many phases are there and why are the phases relevant rather than just asking about "insulin response"?

I have not nly recently seen this "first phase insulin response" phrase mentioned and not with any explanation of what it means
I have tried Google but nonthewiser why it is asked here
Its basically the response of your body (insulin) to high dose of sugar/carbs after a meal. As opposed to basal or 2nd phase which keeps working round the clock to keep your BG in normal limists.
 
That's what my goal is for now hence these questions to set up a path that works for me at least and live a more un- paranoid life :)
I suggest you just crack on and do it, because there will always be something else to be curious or worry about.

Life tends to throw us curved balls. I have found it best not to sit waiting for them to do me a mischief. Not everything in life is predictable. Trust me on that.
 
What is "first phase insulin response", how many phases are there and why are the phases relevant rather than just asking about "insulin response"?

I have not nly recently seen this "first phase insulin response" phrase mentioned and not with any explanation of what it means
I have tried Google but nonthewiser why it is asked here
Phase response means little to Type 1, but for a Type 2 it is akin to the bolus dose of insulin. It is helpful in reducing the peak value of a spike of glucose due to simple carbs, and the second phase follows on and is akin to the basal dose. Actually, it has been discovered that insulin release is actually cyclic with a period of about 2 minutes. The papers discussing this are quite heavy reading, but I have linked them in other threads where they were relevant.

It is common for T2D to lose their Phase 1 response but actually it is not easy to detect this. The problem is that previous research used OGTT tests to trigger the response, but recent research has shown that the delay through digestion reduces the effect and delays the response so it joins and merges into the basal phases.. So it is only 'visible' when triggered by a step function via an iVGTT test.. So, @finsit if you are hoping to see it when using an oral stimulus, it will remain 'missing'. It is also an insulin response so will not be measured by measuring blood glucose. The effect is quite subtle. There was work done by Roy Taylor using IVGTT that was carried out as part of the ND study, but there were only 11 participants and it was a small seperate study.
 
Its basically the response of your body (insulin) to high dose of sugar/carbs after a meal. As opposed to basal or 2nd phase which keeps working round the clock to keep your BG in normal limists.
In some cases, including my own, the level of carb means nothing or very little. The amount of carbs depends on your intolerance to the amount eaten. If I may. An example, to something like oats, higher than normal spike. Potatoes, very high, rice, moderate spike. And portion sizes also comes into it, on again depending on individual.
I have always called it , the first phase insulin response, and because I don't want more insulin, only just enough because of the trigger in the second phase which in my condition is called by my endocrinologist, an overshoot.
So any or very little carb does trigger a poor first phase then an overshoot.
This first phase of insulin, is combined with many other hormones, which are necessary for digestion of which the senses, brain and stimulus.
I do believe before diagnosis, I had very poor health, which included all the symptoms of T2, but unaware of my circumstances, that I was going hypo, my ever changing list of GP's, and even one endocrinologist, didn't have a clue. I know I had insulin resistance, hyperglycaemia, hyperinsulinimia, fatty organs, poor overall digestive issues. Then a list of minor symptoms which filled a foolscap sheet! Then because of the overshoot of insulin which is always, too much. I have episodes of hypoglycaemia.
T2s, who also have a second phase, have a automatic correction because the liver corrects the imbalance, which is glucogenisis, which is the same action as when your energy (glucose) levels drop. I don't have this!

Which is why my GP called me weird! And my endocrinologist confirmed.

For the last century or more, the emphasis has been on research, the finding out what all the hormones and the role they play when in imbalance, finding a treatment for the imbalance, relying on drugs to maintain, rather than cure. Recent research is on the after effects of either hyper or hypo whatever hormonal imbalance, of the condition. But the overriding problem of endocrine conditions is now food is so important to a person's health.
There are so many different conditions that have come to light, due to food, such as eating disorders, allergies, intolerance. I have had lactose intolerance since very young, I have become carb intolerant, which is not a recognised health disorder.
Diabetes especially T2 covers a wide range of types and conditions. And is still confused with T1!
The causes are even more wide ranging.

Because of my rare condition, I had to do the research and discover what and how my body works. Since diagnosis a decade ago, I have a layman's understanding of my condition and because of the parallels between T2 and RH. I can understand the necessity in health management, because of the role that carbs and sugars have if you do have a predisposition to an imbalance in the dysregulation of BG levels.

There has never been enough preventative research into how our modern diets effect a portion of those susceptible patients. Obesity and diabetes have a huge impact on the NHS. And on health.
 
My simplified take on phases, is that when we eat the saliva contains Amylase which tells the system fuel is on the way. So the pancreas releases some Insulin to start working. Then when the body can better detect the levels of Glucose the second phase kicks in to regulate the blood sugar levels. Obviously with Insulin resistance the expected output of Insulin doesn't work as expected, so more is needed to do the job. Hence Hyperinsulimia. As type 2 our levels drop slower than they should as resistance means it takes longer to deposit the Glucose within the tissues.
This to my mind is why low carbing works so well , as we are reducing the Glucose load to a level our second phase response actually handles. Although we still have the slower drop of levels due to resistance, but an insufficient rise to kick in even more Insulin secretion.
 
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