Type 2 progression to insulin

[Smallbrit]

I too am questioning this 'natural progression', or that progression is as inevitably fast as studies say, at least. According to studies, I should have been on insulin 6 years ago.

I have a particular type of T2 - mitochondrial diabetes. But that genetic reason was only diagnosed earlier this year. Studies of MIDD patients like me all specifically say that onset of diabetes is rapid and the patients in the case studies were all on insulin within 2 years of diabetes diagnosis. However, I was diagnosed T2 at the GP 8 years ago now ('young' at 35 then and relatively slim). I've been diet controlled/low carb all that time - HBA1Cs ranging from 46-55 (slight blip of 88 and 73 five years ago at very emotionally trying time where I fell off the low carb wagon).

I was 88 again in April 2021, 2 months after mito diagnosis, which I took extremely badly. This time, for first time ever, the test was from a hospital consultant, who said they'd immediately write to my GP recommending gliclazide - because diet control wasn't working, obviously, just as the literature said. They weren't at all interested in the notion that I'd actually fallen off the wagon again... because with a life-limiting prognosis, who wouldn't et a biscuit or down many packs of them at a time in sadness?

But.... it's end of July, the GP has had no letter, so life is back to low carbing for me, so by the time the next HBA1c comes around I will be back in the low 50s and the hospital consultant will be baffled that I'm not following what the case studies say.

 

[Oldvatr]

I too am questioning this 'natural progression', or that progression is as inevitably fast as studies say, at least. According to studies, I should have been on insulin 6 years ago.

I have a particular type of T2 - mitochondrial diabetes. But that genetic reason was only diagnosed earlier this year. Studies of MIDD patients like me all specifically say that onset of diabetes is rapid and the patients in the case studies were all on insulin within 2 years of diabetes diagnosis. However, I was diagnosed T2 at the GP 8 years ago now ('young' at 35 then and relatively slim). I've been diet controlled/low carb all that time - HBA1Cs ranging from 46-55 (slight blip of 88 and 73 five years ago at very emotionally trying time where I fell off the low carb wagon).

I was 88 again in April 2021, 2 months after mito diagnosis, which I took extremely badly. This time, for first time ever, the test was from a hospital consultant, who said they'd immediately write to my GP recommending gliclazide - because diet control wasn't working, obviously, just as the literature said. They weren't at all interested in the notion that I'd actually fallen off the wagon again... because with a life-limiting prognosis, who wouldn't et a biscuit or down many packs of them at a time in sadness?

But.... it's end of July, the GP has had no letter, so life is back to low carbing for me, so by the time the next HBA1c comes around I will be back in the low 50s and the hospital consultant will be baffled that I'm not following what the case studies say.

I have for some time here discussed that there are two forms of insulin resistance Mitochondrial which interferes with the Krebs (Citric) cycle and this prevents insulin from opening up the cells to allow glucose storage or usage in the muscle tissue, and the other variant which is adipose IR as typified by the recent work of Prof Roy Taylor using the DIRECT study. For a long time, the mitochondrial pathway was thought to be the sole trigger for T2D, but we know more nowadays.

Low Carb diets should help to control both variants but sometimes it may need extra help. As a gliclazide user myself, I find it gives me better control. I found I lost too much weight when I went into ketosis, and as a TOFI I found that uncomfortable especially in the bath.

 

[MrsA2]

I found I lost too much weight when I went into ketosis, and as a TOFI I found that uncomfortable especially in the bath.

Love it!

 

[LittleGreyCat]

Is there much out there that supports underproduction of insulin in type 2 (before the pancreas is thrashed)

I'm not sure how this would be detected because (at least in the UK) there has been no testing for insulin production on diagnosis with T2.

I have seen posts on this forum (and elsewhere in posts and articles) about people over producing insulin, but then how did they know if they weren't tested on diagnosis?
I think a lot of the over production information comes from the likes of Roy Taylor, but I don't have references to hand.

I know that I am not over producing insulin because I had a private HOMA-IR test which showed low normal insulin and slightly elevated BG. However I was on LCHF and possibly in ketosis so my pancreas might have had more capacity if it was poked with a stick.

It would be helpful if someone did a proper study of slim T2s to see if they could identify the underlying causes, but who would fund this?

 

[Fenn]

Personally I feel confident I have been overproducing insulin as both my children at 2ys and 12yrs were diagnosed with hyperinsulinism, the fact my c-pep test showed 0.05 suggests to me its worn itself out. I can't be rare.

 

[HSSS]

I'm not sure how this would be detected because (at least in the UK) there has been no testing for insulin production on diagnosis with T2.

I have seen posts on this forum (and elsewhere in posts and articles) about people over producing insulin, but then how did they know if they weren't tested on diagnosis?
I think a lot of the over production information comes from the likes of Roy Taylor, but I don't have references to hand.

I know that I am not over producing insulin because I had a private HOMA-IR test which showed low normal insulin and slightly elevated BG. However I was on LCHF and possibly in ketosis so my pancreas might have had more capacity if it was poked with a stick.

It would be helpful if someone did a proper study of slim T2s to see if they could identify the underlying causes, but who would fund this?

When I investigated this a few months ago (combined with OGTT) I was told I need to carb up for a minimum of a week, ideally two, so I got a true picture of capacity not just current production. As you say at you were demanding little of your pancreas so it stands to reason it was producing little

It would be helpful for all diabetes, not just slim, diagnosis to include an insulin/c peptide result, not just to confirm diagnosis, rule out LADA but as a baseline for future progression assessment.

 

[Mr_Pot]

The problem with insulin testing is that the test is a snapshot, usually after fasting, but insulin is dynamic, responding to glucose and other triggers. The C-peptide test may identify a lack of insulin to diagnose Type 1 but is unlikely to prove if a Type 2 is just not able to produce enough insulin to meet a particular demand. It is not surprising that people who have a low bg from a very low carb diet will get a good HOMA-IR score. Their pancreas will be producing very little insulin as there is no glucose to get rid of.

 

[zand]

I had a private insulin test done and I was low carbing (less than 50g daily) at the time.

My fasting glucose was 6.38
My insulin level was 22.03
My insulin resistance index ratio was 5.62 (when normal is less than 1.)

Depressing.

 

[Lamont D]

All I can remember is my insulin was tested a couple of times after c-peptide and GAD was done, this was done through a cannula during a extended oral glucose tolerance test. The first was about half an hour in and the second was when I started going hypo.
This was sent to a laboratory specialising in rare tests, and specific details were asked for.
My endocrinologist was pleased with the results because his initial thoughts were that I didn't have diabetes.

The problem with T2, is they are still using a two hour OGTT.
Also, some doctors prefer fasting, and others prefer non fasting.
If they did both, the spike, the insulin resistance and the insulin would show up.
The tracking of more than two hours would show for a good insulin response or a poor insulin response due to the insulin resistance.

Hyperinsulinaemia is one of the symptoms of T2. Too much insulin is bad for you. This causes damage to your organs. The result is in some, a pancreas that burns out.
I just don't understand why T2s are not tested for this

 

[Fenn]

Your not allowed to fast for c-peptide, it has to be 2 hours after your largest meal of the day, or at least supposed to be.

 

[Lamont D]

I have had multiple c-peptide tests. I had six eOGTTs, and every time I fasted.
The reason, my endocrinologist wanted to see the impact of the glucose drink on my blood glucose levels and to see if I had insulin levels that dictated, why I went hypo!

As this was done over three tests and our fasting hba1c levels are normal, why would he wanting to carb up before? The testing was a way to see if there was a reason why I had what is called an overshoot.
The baseline was done in the first test, and the other two were different doses of a drug. Still went hypo!

 

[Fenn]

Fair enough, I stand corrected, just me then

 

[LittleGreyCat]

I had a private insulin test done and I was low carbing (less than 50g daily) at the time.

My fasting glucose was 6.38
My insulin level was 22.03
My insulin resistance index ratio was 5.62 (when normal is less than 1.)

Depressing.

Just looked back at my HOMA-IR.

Fasting BG 7.94
Insulin level 7.17
IR Index 2.28 (normal less than 1)

I still wonder what the result would have been if my BG had been less than 5.9 at the time of the test, which it often is these days.

 

[HSSS]

The problem with insulin testing is that the test is a snapshot, usually after fasting, but insulin is dynamic, responding to glucose and other triggers. The C-peptide test may identify a lack of insulin to diagnose Type 1 but is unlikely to prove if a Type 2 is just not able to produce enough insulin to meet a particular demand. It is not surprising that people who have a low bg from a very low carb diet will get a good HOMA-IR score. Their pancreas will be producing very little insulin as there is no glucose to get rid of.

There are now dynamic HOMA tests out there utilising an OGTT and a series of tests rather than one. There’s a protocol who’s name escapes me right now. I’ll edit if I remember it. They are not cheap. It’s also why I was told to carb up first so this didn’t effect the tests ability to establish capability rather than current requirement.

 

[Mr_Pot]

There are now dynamic HOMA tests out there utilising an OGTT and a series of tests rather than one. There’s a protocol who’s name escapes me right now. I’ll edit if I remember it. They are not cheap. It’s also why I was told to carb up first so this didn’t effect the tests ability to establish capability rather than current requirement.

The “gold standard” method for measuring insulin resistance is the euglycemic-hyperinsulinemic clamp, in which a constant intravenous infusion of insulin is balanced by a simultaneous infusion of glucose in a clinical research setting. Because of the invasive, time-consuming nature of the clamp procedure, it is difficult to use in routine clinical practice or in large epidemiological studies,

 

[Oldvatr]

There are now dynamic HOMA tests out there utilising an OGTT and a series of tests rather than one. There’s a protocol who’s name escapes me right now. I’ll edit if I remember it. They are not cheap. It’s also why I was told to carb up first so this didn’t effect the tests ability to establish capability rather than current requirement.

The term current requirement indicates that the test is measuring the stage-1 insulin response, not the stage-2 basal response. This is useful since generally T2D loses the first response early in the progression, so the OGTT and similar pulse tests are only capable of detecting a delta change above basal level and deduces the strength of it by the time response area under the curve. It is not a measure of static hyperinsulinemia due to a high basal rate or Insulin Resistance except to the initial response, which is usually the mitochondrial IR not the adipose IR/

 

[HSSS]

The “gold standard” method for measuring insulin resistance is the euglycemic-hyperinsulinemic clamp, in which a constant intravenous infusion of insulin is balanced by a simultaneous infusion of glucose in a clinical research setting. Because of the invasive, time-consuming nature of the clamp procedure, it is difficult to use in routine clinical practice or in large epidemiological studies,

Yep. I was merely saying what we are able to access and is a step better than a single homa test that has been the more common option til recently. Not sure the clamp test is available, even privately, outside of research or highly specialised centres is it?

 

[HSSS]

The term current requirement indicates that the test is measuring the stage-1 insulin response, not the stage-2 basal response.

My use of “current requirement” referred to that under the influence of a low carb diet as opposed to one that has higher insulin demands and had nothing to do with the definition you outline.

 

[Oldvatr]

My use of “current requirement” referred to that under the influence of a low carb diet as opposed to one that has higher insulin demands and had nothing to do with the definition you outline.

I still stand by my definition when it comes to the pulse/response tests. The 2hr OGTT is only covering the stage-1 response. A 4hr timespan would start to show part of the basal response but is still insufficient in that respect. It would require monitoring and recording of at least 6 hours to get an idea of the overall IR response. I believe HOMA is similar in its coverage too, it being based on a step change from fasting and limited time recording.

As regards the effect of diet, the Stage-1 response is triggered by amylase, which is in turn triggered by any carbs entering the mouth. It is in the saliva response to dietary carbs. This is a fixed trigger and is not dependent on carb load except in respect of eating and chewing time. But amylase has two stages. the first is as above, the second is the one that occurs in the gut when carbs are detected in the digested food within the gut, and this controls the basal response. This second stage is carb load dependant. There are other enzymes such as lactase, protease, lipase etc that come into play at this stage. This amylase is also GI dependant to a certain extent. It is also food transit time dependant since it occurs mainly in the upper bowel tract, There is a further stage that occurs in the lower bowel that happens as fibre is digested. This last stage is fermentation that produces sugar products to feed the gut fora and enzymes and does not really enter the bloodstream.

Some artificial sweeteners have been shown to trigger an insulin response, and this can lead to raised insulin levels since there are few accompanying carbs to work on. It does not seem to trigger the second stage of amylase and basal insulin since there are no carbs going into the gut. Thus the basal response does not follow.

Since it seems to be the stage 1 response that goes walkabout in T2D, then the OGTT will be mainly showing the start of Stage 2 basal response. It will certainly show if the stage 1 is compromised, or held back by mitrochondrial IR. It will also show if pancreatic insufficiency is present or inhibited by adipose IR but would probably not be suitable for a quantitative evaluation.

 

[LaoDan]

I still stand by my definition when it comes to the pulse/response tests. The 2hr OGTT is only covering the stage-1 response. A 4hr timespan would start to show part of the basal response but is still insufficient in that respect. It would require monitoring and recording of at least 6 hours to get an idea of the overall IR response. I believe HOMA is similar in its coverage too, it being based on a step change from fasting and limited time recording.

As regards the effect of diet, the Stage-1 response is triggered by amylase, which is in turn triggered by any carbs entering the mouth. It is in the saliva response to dietary carbs. This is a fixed trigger and is not dependent on carb load except in respect of eating and chewing time. But amylase has two stages. the first is as above, the second is the one that occurs in the gut when carbs are detected in the digested food within the gut, and this controls the basal response. This second stage is carb load dependant. There are other enzymes such as lactase, protease, lipase etc that come into play at this stage. This amylase is also GI dependant to a certain extent. It is also food transit time dependant since it occurs mainly in the upper bowel tract, There is a further stage that occurs in the lower bowel that happens as fibre is digested. This last stage is fermentation that produces sugar products to feed the gut fora and enzymes and does not really enter the bloodstream.

Some artificial sweeteners have been shown to trigger an insulin response, and this can lead to raised insulin levels since there are few accompanying carbs to work on. It does not seem to trigger the second stage of amylase and basal insulin since there are no carbs going into the gut. Thus the basal response does not follow.

Since it seems to be the stage 1 response that goes walkabout in T2D, then the OGTT will be mainly showing the start of Stage 2 basal response. It will certainly show if the stage 1 is compromised, or held back by mitrochondrial IR. It will also show if pancreatic insufficiency is present or inhibited by adipose IR but would probably not be suitable for a quantitative evaluation.

So, if I wanted to measure IR at home so I can measure progress, is there a way to do this? Maybe measure some cheat meal once per month?