Fructosamine as a better marker of insulin resistance?

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TamaraRC

Established Member (Voting Rights)
After the really interesting recent study by @Chris Ponting showing some markers of insulin resistance in ME patients, the question arises, why would the HbA1c not be indicating insulin resistance in these patients?

I have seen Continuous Glucose Monitor (CGM) charts of people with ME, and there are many who seem to have pre-diabetic fasting glucose on the chart but the HbA1c is normal.

Research by Ron Davis has shown that ME patients have diminished red blood cell deformability.

https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch180469

Red blood cells with diminished deformability have a shorter life span.

HbA1c measures the average glucose level over the past 2-3 months by calculating the percentage of glycated hemoglobin in red blood cells. But if ME red blood cells are less deformable and have a shorter lifespan, this might lower the HbA1c test result.

I have been trying to think of a way to test this theory. Fructosamine is another marker that reflects blood sugar levels over the last 2-3 weeks, based on glycated serum proteins, not red blood cells. Could this give us a more accurate picture of insulin resistance in ME patients?

I am thinking of organising a patient-led project to collect the Fructosamine tests of people with ME. The HbA1c would need to be tested at the same time, to compare.

I have been speaking to the Renegade Research/ Remission Biome group about this as they have already been doing patient-led research.

It might only be worth ME patients who suspect insulin issues doing this test (for example people who do better on low carbohydrate diets or who have higher fasting glucose levels).

I'm interested in people's opinions on this idea.
 
TamaraRC said:
I am thinking of organising a patient-led project to collect the Fructosamine tests of people with ME. The HbA1c would need to be tested at the same time, to compare.
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How would patients test these things? I know that HbA1c is often tested by the NHS, although I have no idea if gender/age have anything to do with who gets tested. But I've never heard of fructosamine testing being done on anyone. Is it tested in blood? If yes, patients will need phlebotomy as well.
 
Arnie Pye said:
How would patients test these things? I know that HbA1c is often tested by the NHS, although I have no idea if gender/age have anything to do with who gets tested. But I've never heard of fructosamine testing being done on anyone. Is it tested in blood? If yes, patients will need phlebotomy as well.
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In the UK you can book and pay for a fructosamine test on Medichecks, and go to a clinic to get the blood test done. But the total cost is £90 and then the HbA1c test would need to be done around the same time, it might be possible to request this with GP. HbA1c can also be done with Medichecks but would cost more.

https://www.medichecks.com/products...J9jySZtCdngemahoWBWTe35a4ogJAVbRoC-yEQAvD_BwE


That might be out of budget for many, and also many severe patients can't visit the clinic. It's cheaper to get tested in the US, so hopefully there will be some people over there who will be interested in testing it.
 
TamaraRC said:
It's cheaper to get tested in the US, so hopefully there will be some people over there who will be interested in testing it.
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I just ordered both those tests. Should get a lab order within a couple days. Although I do worse on low carb, so maybe not ideal to look at.

My last few hbA1C results:

2019/07/19 - 4.8
2022/10/10 - 5.9
2023/10/09 - 5.2
 
Trish said:
I'm not sure what this approach to collecting data will tell us about relevance to ME/CFS, especially if the sample is skewed by encouraging people who already observe reaction to carbs to take part.
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Maybe, is fructosamine significantly higher than one would expect given hbA1C in most people with ME?

A study looking at correlation of the two:
Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study)
Screenshot_20241003-095101.png

I guess trying to see if most people with ME/CFS are below that line. Though probably a based on a correlation from healthy people if that exists.
 
Trish said:
I'm not sure what this approach to collecting data will tell us about relevance to ME/CFS, especially if the sample is skewed by encouraging people who already observe reaction to carbs to take part.
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Well, I assumed people would be likely to self select anyway, as people who have had glucose issues, higher fasting glucose, bad carb reactions would be more likely to suspect insulin resistance and want to take part. So I figured that if I tested a certain number of these people with indicators of insulin resistance and found that they do indeed have high fructosamine levels, then I could do a second round of testing where I ask people without signs of insulin resistance to take part and then we could compare the results.

I thought it would be best to do it this way because the testing is expensive in the UK and someone paying £90 and travelling to a clinic if they have no indicators of high glucose/insulin resistant might be a waste of money. However if we find that the suspected insulin resistance patients have high fructosamine levels, we could then encourage other people with ME to test fructosamine levels, and then we could potentially use this as a way of identifying subgroups. We might even find symptoms correlate with these subgroups.

If people who don't have obvious signs of insulin resistance want to go and get tested, please do, as we can use all the data, so it will be useful, and who knows, they may have high fructosamine! This might be more viable in the US where the testing is cheaper.
 
TamaraRC said:
Oh that's great, look forward to seeing your results!
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Screenshot_20241008-063420.png
Doesn't look to be anything extremely high. Although it is higher than expected from the cancer+diabetes regression line in the post above.

HbA1C: 5.1
Fructosamine: 243

Edit: Another study, this one on people with type I or II diabetes:

Discordance Between HbA1c and Fructosamine: Evidence for a glycosylation gap and its relation to diabetic nephropathy, 2003, Cohen et al

upload_2024-10-8_12-1-53.jpeg

Another, this one includes lower HbA1C scores and diabetics and non-diabetics. I added a white dot for my score.

Corrected Fructosamine improves both correlation with HbA1C and diagnostic performance, 2017, Rodriguez-segade et al

Screenshot from 2024-10-08 08-39-22.png

And since this paper found a higher correlation to HbA1C if adjusting fructosamine using albumin using the equation adjusted_fructosamine = 42 * fructsamine / albumin, I checked it with my albumin level from a little under two months ago: 45 g/L. My adjusted fructosamine is 226.8. White dot placed at that point on the adjusted correlation chart:
Screenshot from 2024-10-08 09-05-36.png

So HbA1C of 5.1 is on the low end for fructosamine of 243 in these populations.

(Also note for your project I still haven't officially been diagnosed by a doctor with ME/CFS, though I do experience delayed PEM. Doc still wants to rule other things out.)
 
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forestglip said:
View attachment 23690
Doesn't look to be anything extremely high. Although it is higher than expected from the cancer+diabetes regression line in the post above.

HbA1C: 5.1
Fructosamine: 243

Edit: Another study, this one on people with type I or II diabetes:

Discordance Between HbA1c and Fructosamine: Evidence for a glycosylation gap and its relation to diabetic nephropathy, 2003, Cohen et al

View attachment 23691

Another, this one includes lower HbA1C scores and diabetics and non-diabetics. I added a white dot for my score.

Corrected Fructosamine improves both correlation with HbA1C and diagnostic performance, 2017, Rodriguez-segade et al

View attachment 23697

And since this paper found a higher correlation to HbA1C if adjusting fructosamine using albumin using the equation adjusted_fructosamine = 42 * fructsamine / albumin, I checked it with my albumin level from a little under two months ago: 45 g/L. My adjusted fructosamine is 226.8. White dot placed at that point on the adjusted correlation chart:
View attachment 23698

So HbA1C of 5.1 is on the low end for fructosamine of 243 in these populations.

(Also note for your project I still haven't officially been diagnosed by a doctor with ME/CFS, though I do experience delayed PEM. Doc still wants to rule other things out.)
Click to expand...


Oh that's great, thanks for posting your results! As you said that you are not sensitive to carbs, it would make sense that your fructosamine level is normal, but it is still good to confirm and not make assumptions. Hopefully I will get some more results soon from people who have signs of insulin resistance/carb sensitivity and then I can compare. It might be the case that there is an ME subtype who might have high fructosamine levels.

If some people with ME do the test and find that fructosamine is high and HbA1c is normal, I might make a questionnaire to work out differences between them and people with normal fructosamine. If I do make a questionnaire I will let you know!
 
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