Time in Range references

Looking up the NICE / NHS and FDA guidance on TIR we find 3.9-10 mmol/L is recommended for diabetics, with a comment that <3.9 mmol/Lis dangerous.
Does anyone know or have references for the clinical studies / peer reviewed papers from which this range was takes? I mean 3.9 is pretty specific - why not just say 4.0?

TheSecretCarbAddict said:

I'm not sure about the lower limit, but I recently listened to The Diabetes Code by Dr Jason Fung and he mentioned that 10mmol/L is renal threshold for blood glucose, i.e., when body starts to expel glucose through urine.

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Thanks @TheSecretCarbAddict, that's exactly the type of biological rationale I'm looking for.
I'm thinking the 3.9 mmol/L is due to induction of counter-regulatory hormones and a side-salad of insulin resistance, but getting this in black and white is really difficult.

TheSecretCarbAddict said:

Just did a search on Google out of curiosity, but no specific research comes up. Nothing apart from the fact that 3.9mmol/L maps to a nice and round number of 70mg/dL. WHO resource I found at the top of my search talks about mean fasting blood glucose metric with normal range of 70mg/dL and 100mg/dL. I guess the 70mg/dL is your nice and round number, but in different measurement systems, and we pick it because anything below it is no longer normal.

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But that's defining the normal by saying anything lower is not normal? It leaves the question of why 70 mg/dL is defined as normal in the first place. There must be a biological rationale for why these figures were chosen.

So far I've heard of a) brain cells die below 3.9, b) it gives us a nice buffer before serious hypos, c) it minimizes development of hypo unawareness and d) BG below 3.9 is likely to trigger counter-regulatory responses. c) and d) are credible reasons - a) might happen at a much lower BG, and b) is a bonus consequence - these are what I'm gong to look for in the literature.

KennyA said:

Bilous and Donnelly's Handbook of Diabetes might be a good place to start. For instance, B&D say that 48 mmol/l was chosen as the automatic diagnosis point because moderate diabetic retinopathy is rare at levels beneath that figure, but incidence rises sharply at higher levels.


PDF here
https://onlinelibrary.wiley.com/doi/book/10.1002/9781118976074

I've seen various population cohort studies of non-diabetic people showing a marked clustering around 38mmol/mol - graph from the Dutch Lifeline study attached as example.

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Doubtless, the consensus recommendations for the range itself and the TIR come from many clinical studies and I was hoping to delve into the NICE/FDA guideline references, and the references cited in those references, to find the original data, but I'll probably end up with some fragment of the Rosetta Stone that I can't understand. So publications like B&D that cite the range and provide rationale are just as good for exemplification and we can add retinopathy to the list with a causal BG (presumably out of range) and a time-frame.

For events happening at certain BGs, I found this in one of the summary references as a guide to some well-known symptoms of hypos and clearly 70 mg/dL (3.9 mmol/L) is depicted as the average BG where glucagon and epinephrine secretion is increased and I assume there's a paper somewhere with the data for this.



This gives me a biological rational for the 3.9 mmol/L border and why it is "dangerous" to go below. I'll go back to the consensus recommendations docs to find out how that "danger" is defined.

In Response said:

Not sure about the 3.9 but my endo once told me our brains need 2.8 mmol/l in order to work properly.
So, I guess the lower limit needs to be higher than this.
I had also assumed that the reason for 3.9 was that it was "anything below 4" but no idea why 4 is relevant apart from being a round number.

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Your endo cites what appears to be a curious number at first - but see the figure in my post above; 2.8 mmol/L corresponds to "decreased cognition, aberrant behavior."

KennyA said:

This is from B&D and it shows the same kind of thing.

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Wow - there's physiological changes to hypo unawareness?! I always though it meant you didn't notice your confusion or lack of concentration, which are taking place anyway - but no, counter-regulatory responses are actually at a lower BG. This makes a mockery of the hypo awareness questionnaires - they should be measuring blood values for glucagon.

My counter-regulatory spikes begin at 5-6 mmol/L and go up to 10 mmol/L - does that make me super hypo aware?