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 isnāt 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 doesnāt change, a sponge thatās 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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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.
I was unaware of endurance exercise potentially leading to longer RBC lifespans. Thatās 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.
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).
Todd
#5
Iām really appreciative of you posting this. Itās the first time Iāve run across this information.
Iām 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.
Itās good to hear Iām 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 āborderline diabeticā when my other numbers are excellent has always been unsettling.
Thank you!
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[quote=āTodd, post:5, topic:20839ā]
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
Todd
#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 āaltitude training,ā but itās at least a little bit relevant from this list.
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