The Paradox of Elevated HbA1c in Elite Endurance Athletes with Optimal Metabolic Health

#1

New article that talks about something that has puzzled me over the last 2-3 years: A1C in the pre-diabetic range, despite low fasting glucose and more importantly, low fasting insulin (I tested for both). One year ago, I was at 5.7, 3 and earlier this year at 5.8 (officially pre-diabetic).

One of the most overlooked factors influencing HbA1c is the biology of red blood cells themselves. Hemoglobin A1c reflects a process called glycation, where glucose binds to hemoglobin, the protein in red blood cells that carries oxygen. This glycation is non-enzymatic and irreversible, meaning that once glucose attaches to hemoglobin, it remains there for the life of the red blood cell. Because the average red blood cell lives around 120 days, HbA1c is interpreted as a reflection of average glucose exposure over the previous two to three months.

But that 120-day assumption isn’t universal. The lifespan of red blood cells can vary depending on several physiological factors, and when they circulate for longer than average, they have more time to accumulate glycation. Think of each red blood cell as a sponge moving through sugar water: the longer it stays in that environment, the more sugar it picks up. Even if the sugar concentration in the water doesn’t change, a sponge that’s been there longer will end up holding more. Similarly, red blood cells exposed to normal glucose levels for an extended period can accumulate more glycated hemoglobin, causing the HbA1c level to appear elevated, even when metabolic health is excellent.

This becomes particularly relevant in the context of endurance-trained athletes. Chronic aerobic training leads to subtle yet significant adaptations in red blood cell physiology. For one, as the body becomes more efficient at delivering oxygen, thanks to increased capillary density, mitochondrial function, and improved oxygen extraction, there is less mechanical and oxidative stress on red blood cells. This allows them to circulate longer before being broken down and replaced. At the same time, consistent training tends to reduce systemic inflammation and upregulate antioxidant defenses, both of which help preserve red blood cell integrity and delay cell turnover. Over time, these adaptations can lead to a population of red blood cells that survives slightly longer than the standard 120 days

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#2

HbA1c has lots of complexities not least the aldimine ketoamine issues. My lowest value was 4.18, but it is now around 4.9-5.0. however, I think my health is better now.

#3

I was unaware of endurance exercise potentially leading to longer RBC lifespans. That’s interesting. I think it depends on the type of endurance exercise though. High impact endurance exercise like running is known to lead to destruction of RBCs in the feet when the heel strikes the ground (they literally explode) so I would expect that running long distances frequently might shorten RBC lifespans which would tend to reduce HBA1c not increase it. But maybe the other factors matter more, or the destruction from running only occurs in extreme endurance athletes.

#4

In this context I wonder if whether some increase in A1c with rapamycin might not be the result of its impact on RBC - if rapa increases RBC lifespans (I have no idea).

#5

I’m really appreciative of you posting this. It’s the first time I’ve run across this information.

I’m an aging endurance athlete, and it has always been a mystery to me why my A1c number remains relatively high (5.6-5.7, depending on which year blood test you look at).

All of my other inflammation and metabolic numbers are excellent, so this A1c number has always been a mysterious outlier.

It’s good to hear I’m not the only one experiencing this incongruence, and that there may be a healthy cause that leads to a different interpretation. The idea of being labeled “borderline diabetic” when my other numbers are excellent has always been unsettling.

Thank you!

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#6

[quote=“Todd, post:5, topic:20839”]
my A1c number remains relatively high

Do you fit into any of the below categories?

ChatGPT o3:
Plausible drivers of a higher HbA1c in athletes

#7

None of the above.

No iron deficiency, no fueling spikes, no adaptive insulin resistance (not a low carb athlete and HOMA varies between .45 and .70 on various blood tests.).

The only thing that may apply is I exercise (trail run, ride, and swim) at around 5,000 feet. But I consider that reasonably under what would be considered “altitude training,” but it’s at least a little bit relevant from this list.

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#8

I recently shared my “unusual” blood markers in a health group discussion (HbA1c elevated at 5.6-5.8, Homa IR excellent at.5-.7, Triglyceride/HDL excellent well below 1, VO2 max from Garmin watch 42 and resting heart rate in low 40s, and almost no plaque with soft at zero and hard at 9) pointing out how my HbA1c is borderline diabetic compared to large population data, but every other marker indicates unusually strong metabolic and cardiovascular health for a 64 year old male.

The inconsistency is my various markers measuring roughly the same thing (metabolic health in one case, and cardiovascular health in another) is striking. One measure will show unusual excellence, and another measure shows significantly worse than average compared to the population.

Coincidentally, someone in the group had just seen this video exactly addressing this topic.

, so I thought I would share it here in case it’s helpful for others. I found it useful for getting some of the subtleties on this topic

Apparently, more research is coming out showing how endurance athletes (I’m a distance runner and distance cyclist) show the exact pattern I’m displaying - meaning the standard of judgment needs to be different from large population standards.

Similarly, the other unusual marker I deal with is elevated LDL such that doctors want to put me on statins until they see my data - zero soft plaque, only a 9 on hard plaque score, and the blood brain barrier is perfectly healthy with no white spotting in the Neuroquant exam. In other words, zero cardiovascular issues at age 64 from a lifetime of significantly elevated LDL?!? Go figure…

I share all this in case it’s helpful for others in a similar situation. The more I understand about deeper health topics, the more I become interested in finding metrics developed from a population of extremely health people. The large population standards just don’t cut the mustard, and there’s a lot of individual variation from “average” that don’t necessarily imply poor health.

For example, it’s a near certainty that my unusual HbA1c is connected to my exercise practices and is absolutely not a problem indicator for my metabolic health. That’s understood well enough by science now that I’m comfortable with it.

However, it’s not nearly as clear about the elevated LDL. Could be genetics (but that’s unlikely because my brother only 4 years older than me is already dead after a triple-bypass years earlier and a lifetime of extensive cardiovascular problems), so it’s likely something else in my lifestyle practices. They really don’t know, but they do know that LDL is only 30% correlated with cardiovascular disease and Triglyceride/HDL is more than 70% associated. Hmmm…

My point is not my personal issues, but using my personal data points to to show the limitations of large population data as a comparison point. It’s not a throwaway, but it’s also not nearly as determinant as conventional analysis would imply when your numbers contrast with norms. The difference in your numbers could be a good thing, or they could be a bad thing. And the state of the science is still so early that it’s hard to get the distinctions.

Anyway, just sharing my learning journey from my own misadventures with my personal numbers in case it is helpful for others having a similar experience. I worried for years about my elevated HbA1c only to learn recently that it’s actually a good thing. Wow!

Similarly, I worried for years about my elevated LDL, but the more I’ve learned the more I realize the “high LDL is bad” framework is far from complete. Again, it’s not a throwaway, but there are so many inconsistencies in the research data that some other dynamic will emerge in future years that better fits the full picture. We just aren’t there yet.

What I’ve come to learn is these personal deviations in my blood markers are 100% expected when my life practices are significantly different from the general population (which of course, is most people in this community.)

I hope the above video resource and sharing my personal learning journey about unusual blood markers is helpful.

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