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HbA1c: What's Optimal, What's My Data?


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A great video as always Michael! I am curious if you have any speculation on why a HBA1C of less than 5.0% is associated with an increase in all-cause-mortality as this surprises me a little.

It certainly isn't a surprise that a HBA1C of greater than 6.5% is associated with a 71% increase in ACM, or that an HBA1C of 6.0-6.5% is associated with a 16% increase in ACM. The idea of a "survivor bias" representing the decline in HBA1C in 70+ year old adults is interesting. 

Out of curiosity I pulled my own data to see where I land. I don't have nearly as many data points as you, but some are better than none!

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IMHO, the answer on

Quote

I am curious if you have any speculation on why a HBA1C of less than 5.0% is associated with an increase in all-cause-mortality as this surprises me a little.

is frailty as both the sign (the body is not managing the stable state of energy quickly available at a fast disposal/refeeding of many cells that could require it) and the risk for dangerous events (hypoglycaemia per se and its consequences).

For t2dm here are useful details https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099963/

Also the second contributing factor could be RBC residence time, HbA1c is known to be biased towards the lower value in people with higher RBC rotation time which itself is not a good sign, the lifetime of these cells is a kind of "hard wired" via molecular machinery and those who have very low HbA1c could have it not because of glucose factor but due to quick RBC disposal caused by other reasons, not any of them seems wanted.

But these are speculations, it is hard to assess the volatile parameter that depends on other volatile things also.

Maybe centenarians HbA1c is a better thing to target but here the question rises - at what their age and how it has to be aligned with their other markers

Br,

Igor

 

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Hey drewab, I'm not sure why < 5% is associated with an increased ACM risk, but reverse causation could be involved, especially in terms of liver dysfunction. If so, I'd expect gluconeogenesis to be impaired, blood glucose to be low (< 80), and correspondingly, low HbA1c.

What were your liver biomarkers for those tests? ALP, AST, ALT, albumin, bilirubin? If they look youthful, I wouldn't worry about the HbA1c metaa-analysis data.

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