C peptide test and Medication

[GDM06]

I am thinking I may get a better response from a LADA forum.
I have a quick question- If you are LADA, but previously treated as type 2, did you have to stop your medications before the C-peptide test?
I want to do the C- peptide test and concerned GLP-1 agonist may give a false positive result. Should the medication be stopped before C- peptide?
If so how long? I am on daily dosing of GLP-1 agonist.
I am planning to do the C peptide privately, as I can get the same done via work, but can't get GAD antibodies as the sample needs to be frozen for that and we don't have that facility at work.

Thanks in advance

 

[Antje77]

I want to do the C- peptide test and concerned GLP-1 agonist may give a false positive result. Should the medication be stopped before C- peptide?
If so how long? I am on daily dosing of GLP-1 agonist.

C-peptide is not a positive/negative result, it's a test showing how much insulin you produce. So ignoring different types of diabetes like MODY or T3C, there are basically 3 possibilities:
High C-peptide: Most likely T2, overproducing to try to keep BG low despite insulin resistance.
Low C-peptide: Most likely T1/LADA (which is T1 as well).
In the normal range: Can be both early LADA or well controlled low carbing T2, or long standing T2.

What the normal range is is also dependent on what your BG is at the moment of testing.
If your C-peptide is on the lower end of normal but your BG is fine because you didn't have any carbs, it shows that the amount of insulin you produced was the right amount, you didn't need more.
But if your C-peptide is smack in the middle of normal while having very high BG, it looks like you're underproducing, which could be part of a LADA diagnosis.

Have you considered asking for a referral to an endocrinologist to get those tests including the knowledge to interpretate?
I had my C-peptide tested when I had already been on insulin for two years, and I was very happy to have an endo to go over the results with me, they weren't straightforward and there was room for interpretation.

I'm not sure how a GLP-1 agonist would affect a C-peptide test.
@Oldvatr , you're good with digging through literature, have you come across anything about this?

 

[GDM06]

C-peptide is not a positive/negative result, it's a test showing how much insulin you produce. So ignoring different types of diabetes like MODY or T3C, there are basically 3 possibilities:
High C-peptide: Most likely T2, overproducing to try to keep BG low despite insulin resistance.
Low C-peptide: Most likely T1/LADA (which is T1 as well).
In the normal range: Can be both early LADA or well controlled low carbing T2, or long standing T2.

What the normal range is is also dependent on what your BG is at the moment of testing.
If your C-peptide is on the lower end of normal but your BG is fine because you didn't have any carbs, it shows that the amount of insulin you produced was the right amount, you didn't need more.
But if your C-peptide is smack in the middle of normal while having very high BG, it looks like you're underproducing, which could be part of a LADA diagnosis.

Have you considered asking for a referral to an endocrinologist to get those tests including the knowledge to interpretate?
I had my C-peptide tested when I had already been on insulin for two years, and I was very happy to have an endo to go over the results with me, they weren't straightforward and there was room for interpretation.

I'm not sure how a GLP-1 agonist would affect a C-peptide test.
@Oldvatr , you're good with digging through literature, have you come across anything about this?

Thanks so much. I am booked to see my endocrinologist on the 29th of June. So maybe I will wait and discuss it with him.
The background is the diagnosis of Gestational Diabetes at 25y/o and 30y/o, 23 weeks gestation the first time and 2nd by 18 weeks gestation. On insulin both times.
Then 37y/o, I diagnosed myself with Diabetes as I was symptomatic, and so did HBA1C at work 79. I did see my endocrinologist at that stage and he just said type II DM may be LADA, but even if LADA is likely early stages. He suggested lifestyle changes and metformin. Couldnt tolerate metformin and initially tried this with my second pregnancy couldn't tolerate same.
Essentially convinced GP to start me on GLP-1 agonists. Work for a fair bit, and now in my 40s and despite low carb 50g or less. Fasting blood 9-11 on the same dose of 1.2g Victosa. I am now on 20-30g carb and 1.8g Victosa fasting a bit better most days, its around 7. Myy concern is about low production of insulin, and maybe I am pushing the islets a bit too much.
I just can't tolerate even a little bit of carb without significant rise in BG. By the way, I am a normal weight for my height.
In pregnancy, my fasting glucose was very difficult to control they just kept increasing the Basal dose of Insulin.

 

[Antje77]

Thanks so much. I am booked to see my endocrinologist on the 29th of June. So maybe I will wait and discuss it with him.

I am planning to do the C peptide privately, as I can get the same done via work

If you can easily do the C-peptide through work, you could consider doing it anyway and make sure to record your BG at the moment of the test.
That will put you one step ahead for your conversation with the endo.

 

[EllieM]

Is it worth doing a cpeptide fasting? Then you don't have to worry about the influence of carbs....
(Edited to add, wild guess based on the fact that labs seem to quote normal ranges as being fasting or non fasting

 

[Antje77]

Is it worth doing a cpeptide fasting? Then you don't have to worry about the influence of carbs....
(Edited to add, wild guess based on the fact that labs seem to quote normal ranges as being fasting or non fasting

From what I remember (but I did the reading up on the subject a few years back, no guarantee I remember correctly!) a random C-peptide is best taken with a BG of at least 8 mmol/l, a number where your pancreas is supposed to be producing substantial insulin. With a low number plus low C-peptide the low C-peptide doesn't tell you much except that you're not overproducing at that moment.

I think there are also stimulated C-peptide tests, don't know anything about it though.
Like I said, C-peptide is not a straightforward positive or negative test, it takes knowledge I don't have to interpret, unless the results are at the extreme ends of the scale.

 

[Oldvatr]

C-peptide is not a positive/negative result, it's a test showing how much insulin you produce. So ignoring different types of diabetes like MODY or T3C, there are basically 3 possibilities:
High C-peptide: Most likely T2, overproducing to try to keep BG low despite insulin resistance.
Low C-peptide: Most likely T1/LADA (which is T1 as well).
In the normal range: Can be both early LADA or well controlled low carbing T2, or long standing T2.

What the normal range is is also dependent on what your BG is at the moment of testing.
If your C-peptide is on the lower end of normal but your BG is fine because you didn't have any carbs, it shows that the amount of insulin you produced was the right amount, you didn't need more.
But if your C-peptide is smack in the middle of normal while having very high BG, it looks like you're underproducing, which could be part of a LADA diagnosis.

Have you considered asking for a referral to an endocrinologist to get those tests including the knowledge to interpretate?
I had my C-peptide tested when I had already been on insulin for two years, and I was very happy to have an endo to go over the results with me, they weren't straightforward and there was room for interpretation.

I'm not sure how a GLP-1 agonist would affect a C-peptide test.
@Oldvatr , you're good with digging through literature, have you come across anything about this?

Not sure it has been studied. Going by the mechanism of the GLP-1 meds, it does force the pancreas to output high insulin since GLP-1 is the hormone that kicks the beta cells into action. Normally the natural way of things (no med) glucagon will rise as glucose lowers, and this regulates the insulin output by reducing the GLP-1 signal. but the argonist is mimicking the GLP-1 and forces the beta cells to keep on churning so that ketosis is triggered instead. So I would imagine the effect of the med would be to squeeze insulin out at max rate while the med is active. I imagine it would deffo affect the c-pep test. In many respects it is similar to the sulfonylurea drugs like Gliclazide, but is more of a spanner in the works (Glic only lasts about 3 hours, Ozempic lasts 5 or more days).

 

[Oldvatr]

My post about the action of the GLP-1 meds has reminded me of an elephant in the room that no one seems to be abke to see.

I am using Gliclazide which boosts pancreas output by emulating the output signals from the delta cells, which is what they naturally do anyway. but that class of meds also puts a spanner into the works like the GPL-1 meds do.

Now sulofnylurea meds are known to thrash the pancreas, and hasten beta cell aptosis (i.e. it kills them off through overworking them). So it stands to be worth considering if the GLP-1 meds will also lead to early loss of pancreas function. we do not know since these meds are very new, and there is no long term history to look back over,

Since we do not use c-peptide to monitor this effect we have no proof yet either way, but I am worried that users of these meds may find that their long term prognosis is destined to be short. Especially where the normal treatment plan is being touted as 2 years at least. There is no long term monitoring in place at all.

This worry is already irrelevant to T1D and some other ID users who already have little or no pancreas output to thrash. But T1D and T2D in the honeymoon phase may find it hastens the progression.

 

[Antje77]

Now sulofnylurea meds are known to thrash the pancreas, and hasten beta cell aptosis (i.e. it kills them off through overworking them).

I thought this was a theory without consensus yet?

 

[Oldvatr]

I thought this was a theory without consensus yet?

It was proven for the first generation sulfonyls, and most were withdrawn. second generation ones are still used, but are not a primary treatment.

Only gliclazide has a 'no known association' tag. It is a new generaton of the drug.

Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose - PubMed

Therefore, gliclazide protected human beta-cells from apoptosis induced by intermittent high glucose, and this effect was likely to be due, at least in part, to the anti-oxidant properties of the molecule.

pubmed.ncbi.nlm.nih.gov

 

[Fenn]

Hi, I am Not sure about the meds you take but my C-Pep test said I had to test two hours after my biggest meal of the day, I took this as code for “I should eat double sausage McMuffin meal with hash brown” (lol) my result was 0.05 somethings, this made them change my diagnosis but I’m still not convinced I’m T1.5 because I have no trust left after being treated as T2 for 4 or 5 years, I do get treated better now, T2 me was treated terribly by the system so for that reason alone it’s worth trying to get your correct diagnosis, plus you get Libre on prescription. best Of luck

 

[GDM06]

Hi, I am Not sure about the meds you take but my C-Pep test said I had to test two hours after my biggest meal of the day, I took this as code for “I should eat double sausage McMuffin meal with hash brown” (lol) my result was 0.05 somethings, this made them change my diagnosis but I’m still not convinced I’m T1.5 because I have no trust left after being treated as T2 for 4 or 5 years, I do get treated better now, T2 me was treated terribly by the system so for that reason alone it’s worth trying to get your correct diagnosis, plus you get Libre on prescription. best Of luck

Thanks so much. I had the impression that the result may be affected by meds. I get Dexcom G7 on prescription here in Ireland. I think it may be because I have been on insulin in the past (when I was pregnant). I have been using the CGM now to get a lot more clarity.

 

[GDM06]

My post about the action of the GLP-1 meds has reminded me of an elephant in the room that no one seems to be abke to see.

I am using Gliclazide which boosts pancreas output by emulating the output signals from the delta cells, which is what they naturally do anyway. but that class of meds also puts a spanner into the works like the GPL-1 meds do.

Now sulofnylurea meds are known to thrash the pancreas, and hasten beta cell aptosis (i.e. it kills them off through overworking them). So it stands to be worth considering if the GLP-1 meds will also lead to early loss of pancreas function. we do not know since these meds are very new, and there is no long term history to look back over,

Since we do not use c-peptide to monitor this effect we have no proof yet either way, but I am worried that users of these meds may find that their long term prognosis is destined to be short. Especially where the normal treatment plan is being touted as 2 years at least. There is no long term monitoring in place at all.

This worry is already irrelevant to T1D and some other ID users who already have little or no pancreas output to thrash. But T1D and T2D in the honeymoon phase may find it hastens the progression.

Thanks, I know it induces insulin production but unlike sulphonylureas. Its effect is mainly triggered with meals, hence its advantage over sulphonylureas. But I believe most of the type 2 meds, in the long run, will not be suitable for Type 1.5.
I will do as Antje77 suggests, do the C peptide result at work and record my BM, I may hold off my GLP-1 agonist the night before as I am on daily dosing. I believe half-life of Victosa is 12hrs.

 

[GDM06]

Thanks everyone for your input, very much appreciated!

 

[Oldvatr]

Thanks, I know it induces insulin production but unlike sulphonylureas. Its effect is mainly triggered with meals, hence its advantage over sulphonylureas. But I believe most of the type 2 meds, in the long run, will not be suitable for Type 1.5.
I will do as Antje77 suggests, do the C peptide result at work and record my BM, I may hold off my GLP-1 agonist the night before as I am on daily dosing. I believe half-life of Victosa is 12hrs.

The GLP-1 argonists are not triggered by eating. They mimick the GLP-1 peptide (which does naturally respond to food intake in the gut) but it is there constantly as soon as the injection goes in until it gets used. The GLP-1 mimick latches on to the receptors in the beta cells regardless of glucose levels. It overrides the normal natural GLP-1.

I have to time my dose of Gliclazide to be 20 minutes before I eat to get best effect. I have tried using it as a correction med to reduce a high level by taking extra outside mealtimes and it does nothing to the levels. So Glic seems to only work when there is a demand for insulin which is how the delta cells that usually synthesise sulfonylurea for us, function normally.

Sulphonyl drugs do not contain that peptide, but get their name from the outcome i.e. stimulating the delta cells to increase output. GLP-1 argonists contain a molecule that pretends it is that peptide and it actually latches into the GLP-1 receptors in the beta cell. This is the same mechanism used by the Covid Vaccines.

 

[DEBBIESCOTT]

The GLP-1 argonists are not triggered by eating. They mimick the GLP-1 peptide (which does naturally respond to food intake in the gut) but it is there constantly as soon as the injection goes in until it gets used. The GLP-1 mimick latches on to the receptors in the beta cells regardless of glucose levels. It overrides the normal natural GLP-1.

I have to time my dose of Gliclazide to be 20 minutes before I eat to get best effect. I have tried using it as a correction med to reduce a high level by taking extra outside mealtimes and it does nothing to the levels. So Glic seems to only work when there is a demand for insulin which is how the delta cells that usually synthesise sulfonylurea for us, function normally.

Sulphonyl drugs do not contain that peptide, but get their name from the outcome i.e. stimulating the delta cells to increase output. GLP-1 argonists contain a molecule that pretends it is that peptide and it actually latches into the GLP-1 receptors in the beta cell. This is the same mechanism used by the Covid Vaccines.

I wouldn’t advocate anyone trying this, but if my levels don’t go down where I want them to be I find a small amount of protein i.e a bit a cheese kickstarts the gliclazide & blood sugars lower

 

[GDM06]

The GLP-1 argonists are not triggered by eating. They mimick the GLP-1 peptide (which does naturally respond to food intake in the gut) but it is there constantly as soon as the injection goes in until it gets used. The GLP-1 mimick latches on to the receptors in the beta cells regardless of glucose levels. It overrides the normal natural GLP-1.

I have to time my dose of Gliclazide to be 20 minutes before I eat to get best effect. I have tried using it as a correction med to reduce a high level by taking extra outside mealtimes and it does nothing to the levels. So Glic seems to only work when there is a demand for insulin which is how the delta cells that usually synthesise sulfonylurea for us, function normally.

Sulphonyl drugs do not contain that peptide, but get their name from the outcome i.e. stimulating the delta cells to increase output. GLP-1 argonists contain a molecule that pretends it is that peptide and it actually latches into the GLP-1 receptors in the beta cell. This is the same mechanism used by the Covid Vaccines.

100% tell you that insulin is not triggered constantly with GLP-1 agonist as in sulphonylureas. I have done a lot of literature reviews on GLP-1 agonists and my background is research.
When you take GLP-1 agonist you don't get an instant reduction in blood sugar as you do with sulphonylureas.
I am not saying GLP-1 agonist does not stimulate insulin production in the absence of food, but it's effect is more pronounced in the presence of food. The effect is different from Sulphonylureas.
You check out - Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014 Sep;15(3):181-7. doi: 10.1007/s11154-014-9289-5. PMID: 24811133; PMCID: PMC4119845.
The exact word here - GLP-1 enhances insulin secretion and inhibits glucagon-release in a glucose-dependent manner both in normal individuals as well as in patients with type 2 diabetes. It works in a glucose-dependent manner.

 

[GDM06]

The GLP-1 argonists are not triggered by eating. They mimick the GLP-1 peptide (which does naturally respond to food intake in the gut) but it is there constantly as soon as the injection goes in until it gets used. The GLP-1 mimick latches on to the receptors in the beta cells regardless of glucose levels. It overrides the normal natural GLP-1.

I have to time my dose of Gliclazide to be 20 minutes before I eat to get best effect. I have tried using it as a correction med to reduce a high level by taking extra outside mealtimes and it does nothing to the levels. So Glic seems to only work when there is a demand for insulin which is how the delta cells that usually synthesise sulfonylurea for us, function normally.

Sulphonyl drugs do not contain that peptide, but get their name from the outcome i.e. stimulating the delta cells to increase output. GLP-1 argonists contain a molecule that pretends it is that peptide and it actually latches into the GLP-1 receptors in the beta cell. This is the same mechanism used by the Covid Vaccines.

Just to give you more information on this

Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence. Diabetes Obes Metab. 2013 Jan;15(1):15-27. doi: 10.1111/j.1463-1326.2012.01663.x. Epub 2012 Aug 1. PMID: 22776039; PMCID: PMC3556522.

Stimulation of insulin secretion from pancreatic β-cells by glucagon-like peptide 1 receptor (GLP-1R) agonists is known to be glucose-dependent. GLP-1R agonists potentiate glucose-stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations.

It's extremely rare to get hypos on GLP-1 agonists for this reason, unlike the effect with sulphonylureas!

 

[Oldvatr]

100% tell you that insulin is not triggered constantly with GLP-1 agonist as in sulphonylureas. I have done a lot of literature reviews on GLP-1 agonists and my background is research.
When you take GLP-1 agonist you don't get an instant reduction in blood sugar as you do with sulphonylureas.
I am not saying GLP-1 agonist does not stimulate insulin production in the absence of food, but it's effect is more pronounced in the presence of food. The effect is different from Sulphonylureas.
You check out - Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014 Sep;15(3):181-7. doi: 10.1007/s11154-014-9289-5. PMID: 24811133; PMCID: PMC4119845.
The exact word here - GLP-1 enhances insulin secretion and inhibits glucagon-release in a glucose-dependent manner both in normal individuals as well as in patients with type 2 diabetes. It works in a glucose-dependent manner.

I agree that GLP-1 acts as you quote above, but that is the natural peptide from the alpha cells. I am talking the incretin mimic of the argonist med. I have not seen anything that shows that its action is regulated in the same way natural GLP-1 is regulated by glucagon etc. What is the mechanism of control once it is in the blood from the injection? What turns it down or turns it off except normal use and excretion which for Trulicity is a period of 11 hours at least, compared to GLP-1 natural which only lasts 11 minutes in the blood.

The paper you quote is behind a paywall, and I can only access the abstract which is not very helpful.

 

[Oldvatr]

Just to give you more information on this

Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence. Diabetes Obes Metab. 2013 Jan;15(1):15-27. doi: 10.1111/j.1463-1326.2012.01663.x. Epub 2012 Aug 1. PMID: 22776039; PMCID: PMC3556522.

Stimulation of insulin secretion from pancreatic β-cells by glucagon-like peptide 1 receptor (GLP-1R) agonists is known to be glucose-dependent. GLP-1R agonists potentiate glucose-stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations.

It's extremely rare to get hypos on GLP-1 agonists for this reason, unlike the effect with sulphonylureas!

The paper states AS FACT the GLP-1r is controlled by glucose levels, which is true for the GLP-1r obtained by cleavage within the alpha cells, but I am not convinced that the incretin mimic injected and free roaming in the blood is similarly controlled. Certainly the alpha cells reduce production of GLP-1 products as Glucagon rises and glucose levels drop (normal operation) so the insulin demand signal is indeed normally controlled by glucose levels and the cleavage process, this does not IMO apply to the fake GLP-1 flooding the pancreas from the injection.

You are right that something does appear to limit the capacity of this med to induce hypoglycemia, but until I see some graphs of insulin or c-pep then I will remain sceptic. Do you have access to any studies that do this?

Note that the pancreas is still producing Glucagon as glucose levels fall, and this will trigger ketosis instead of glucose secretion. This also needs insulin to be present and ,maybe this is the limiting effect. The insulin may still be there but is anyone researching and monitoring for this?

We know this class of meds does induce ketosis which is part of the weight loss success story. There is a new variant from Eli Lilly that adds Glucagon to the injection, and they claim 25% weight loss as compared to the 15% of drugs like Ozempic. So this would be in line with my surmising in the previous para.