HbA1c: do the latest BG samples count for more?

[Michel]

@oni, I just read in detail the references you gave in your justification of your statement that HbA1c is backwards weighted.

1. Your first paper I could not get to, as it is, as you indicated, behind a paywall.

2. Your diabetes Care 1995 article, of which you write:

@oni

Here is a classic, old article in Hba1c kinetics that says the first 2 months of the period are most important:

But the article actually says the exact opposite of your statement:

The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. […]
The lengths of the periods over which the weight function[…] for HbA1c [… was] estimated to be roughly 100 days […].
CONCLUSIONS The level […] of HbA1c [does] not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.

Translation: what this means is that the HbA1c is a weighted average of the past blood glucose levels, and the weight of the most recent samples is highest (“weight functions for glycated proteins had maximum values on the days just before the measurement”).

3. Your PMC article, of which you wrote:

@oni

And if you look at Figure 5 in this article, you’ll also see how the first 60 days of the 120+ day period (some RBCs last longer than you think!) account for most of the change.

But, when I read through the paper, again it actually expresses the exact opposite of what you wrote. In the quote below, the authors discuss Figures 5A-C, with profiles having the SAME 120-day average glycemia:

Based on these figures it can be observed, for example, that 60 days after a drop of BG from 22.2 mmol/l to 5.6 mmol/l, HbA1c is equal to 7.9% (62 mmol/mol), whereas 60 days after a rise in BG from 5.6 mmol/l to 22.2 mmol/l, HbA1c is equal to 12.5% (113 mmol/mol), despite the same average 120-day glycemia in both cases.

What this means:

• in case 1, the first 60 days were high, the last 60 days were low, HbA1c = 7.9%
• in case 2, the first 60 days were low, the last 60 days were high, HbA1c = 12.5%
  Conclusion: the last 60 days were much more important than the first 60 in both cases for HbA1c, despite the same average glycemia in both cases

On that basis, I don’t think we need to do any simulation, since all the references say the same thing: it is the later part of the last 120 days that is preponderant in the measurement of average glucose by the HbA1c.

But I am disappointed that your interpretations of the quotes you gave us were the opposite of what they really mean Readers cannot always review every single reference given, and need to be able to trust someone’s interpretation of them. This makes me doubt the meaning of the other references you gave in other current threads, especially on the heels of this other instance where the reference you gave was also different from the interpretation you gave of it:

Is a lower HbA1c always better?

The study says this: “The observed CVD risk among people with low HbA1c levels and no known diabetes is particularly important, because this increased risk could not be related to hypoglycemia11 “ They’ve reached the exact opposite conclusion. " Furthermore, the patterns of the association between low HbA1c levels and each CVD subset differed from that for diabetes or high HbA1c levels. Low HbA1c levels were associated with an increased risk of stroke, especially hemorrhagic stroke, while di…

So I think it is really important to read through a study and understand it thoroughly before quoting it for a purpose! Not that I have not been caught by that before…

As for the point of this thread, I want to make sure to repeat the conclusion here for any stray reader:

The HbA1c is biased towards the latest part of the last 120 days of average glucose levels. The last 60 days count for more than the first. The last 30 count for more than the next 30, etc.