Eva: Hemoglobin A1c So I'm playing with a continuous
glucose monitor since like 17 months, and my glucose is around the average glucose.
It's under 100.
It could be 90 for three months, and then I try to figure something out, I can go up
to 95, 97.
If I'm spiking, I'm spiking maybe 152, but for only five minutes or 10, let's say 10
maximum.
And then goes back right how it's supposed to be.
But my hemoglobin A1c it's always coming back high, so between 5.5 and 5.6 every time.
Chris Masterjohn: The continuous glucose monitor trumps the
HbA1c, hands down, and makes it irrelevant because the point of HbA1c is that it is a
useful but imperfect marker of cumulative past glucose exposure.
And you are actually completely tracking all of your glucose exposure.
It's completely pointless to measure HbA1c if you have a continuous glucose monitor because
you're using something that is an imperfect marker to try to make an inference about something
where you have the exact data of.
It's like calculated LDL cholesterol and exact LDL cholesterol.
If you had them measured in the same test and the calculated one looked bad and the
exact one looked good, you would ignore the calculated one because the calculation isn't
perfect, and obviously it's wrong.
But the reason is that HbA1c is subject to two other determinants besides cumulative
past glucose exposure.
One is red blood cell turnover.
Chris Masterjohn: Well, first of all, probably wearing a continuous
glucose monitor actually increases your red blood cell turnover because you're taking
little dips of blood all the time, right?
Eva: Mm-hmm.
Chris Masterjohn: I don't know what the volume of that is, but
if you...
Wait.
Is it taking blood?
Eva: No, it's just a sensor.
Chris Masterjohn: Oh, it's just infrared or something like that,
right?
Eva: It's not a needle.
Chris Masterjohn: So I take that back.
Things that we know can increase your red blood cell turnover include exercise, include
any kind of blood loss, right?
So if you have a heavier period or you're running a lot of lab tests or you donate blood,
all of these things can increase your red blood cell turnover.
And then there's also just other determinants of red blood cell turnover that are unknown.
So just probably for genetic reasons or hormonal reasons or whatever it is, some people just
have higher red blood cell turnover than other people, and it's a confounder.
Chris Masterjohn: Then the second thing is that you actually
have an enzyme called fructosamine-3-kinase that deglycates hemoglobin.
And there are some things that might impact that, but there's also a strong genetic component.
I don't know if you can get that measured with a test, but in research, they can test
it.
And there's a very significant correlation, inverse correlation, between fructosamine-3-kinase
activity and HbA1c, where HbA1c goes down if that enzyme is high.
And if that enzyme is low, HbA1c goes up.
Chris Masterjohn: So you're taking this HbA1c measurement, which
in you is a little bit high, and there are three possible interpretations.
One is that your cumulative blood glucose exposure over the last 48 weeks is high, in
the prediabetic range.
Another is that your red blood cell turnover is a little bit lower than average.
And a third is that your fructosamine-3-kinase activity is a little bit lower than average.
And you've ruled out the first one because your continuous monitor shows that that's
not true.
And therefore, you know it's one or two of these other confounding factors that makes
HbA1c borderline useless in some cases, such as yours.
Eva: And is this good to explore why it's happening?
Or I would just not?
Chris Masterjohn: I'm sorry.
What'd you say?
Is it going to explode?
Is that what you said?
Eva: No.
Is this good to explore the other two options that we know?
Chris Masterjohn: Oh, to exclude them.
Eva: Or you would not get a-
Chris Masterjohn: Is there a way to rule in or out those other
two options?
Is that what you're asking?
Eva: Yes.
Chris Masterjohn: Okay.
I don't think so.
I mean, there's no direct test for red blood cell turnover, as far as I know.
I mean, I don't know if some obscure lab offers one, but it's not a usual test that you would
get.
I'm trying to think if you could infer it from...
I don't really think you could get a good inference, even from anything on a complete
blood count, actually.
So I think it would make sense to consider that if you have...
Let's say you become menopausal or have amenorrhea or have a lighter period than average, then
that would be one thing that would raise HbA1c.
And then if you, I don't know, haven't been exercising...
Let's say you go from a more active period to a less active period, and then it goes
up a little bit, that would probably be a contributor to that.
Chris Masterjohn: I don't know.
I don't think anyone offers a commercial test for fructosamine-3-kinase activity.
Maybe there are some snips that are in 23andMe or something like that, but I don't know that's
the case.
I doubt it is.
No one's diagnosing it for any reason.
But if I have time at some point, and I find that there are any ways to look at either
of these things, I'll post about it, but I don't think so.
Eva: Thank you.
Chris Masterjohn: Yeah.
Eva: Thank you so much.
Chris Masterjohn: Thank you for your question.
Appreciate it.
Eva: Thank you.