HBA1c, what is ideal

[Orangeblossom]

This paper http://care.diabetesjournals.org/conten ... l-text.pdf is about ranges of HB1AC. It is interesting to see they found a curve which showed excess mortality at lower as well as higher levels.

Wonder what this means in terms of levels for us as i thought it was simply lower the better. Maybe that is not the case and there is a range to aim for.

[circular]

Thanks for bringing this up. I remember coming across this notion some time ago and periodically wonder. I can only inch the conversation along since I shouldn't take time to read the whole paper, but note my highlighted text in the abstract:

RESULTS
Excess mortality risk was observed for participants with known diabetes (hazard ratio 1.41 [95% CI 1.08–1.84]) and undiagnosed diabetes (1.63 [1.23–2.17]) but not for those with high (1.02 [0.80–1.30]) or very high diabetes risk (0.87 [0.67–1.13]). Spline models revealed a U-shaped association, with lowest risk at HbA1c levels 5.4–5.6% (36–38 mmol/mol) and a significantly increased risk at £5.0% (£31 mmol/mol) and ‡6.4% (‡46 mmol/mol).
CONCLUSIONS
Unlike known and undiagnosed diabetes, HbA1c levels in the prediabetic range were not associated with an increased mortality risk. The observed U-shaped relationship adds to existing evidence that not only high but also low HbA1c levels might be associated with all-cause mortality.

The abstract suggests in Results that there were no mortality risks in the participants who didn't have diabetes, but probably someone needs to digest the paper itself? Having made this suggestion in the Results section, the Conclusion then goes on to paint a very broad brush. My vote is that this is a pretty poorly worded abstract and the paper needs digesting.

There's also this statement at Choosing Wisely: Avoid using medications other than metformin to achieve hemoglobin A1c<7.5% in most older adults; moderate control is generally better While specifically addressing the older population and use of glucose lowering drugs, it says:

There is no evidence that using medications to achieve tight glycemic control in most older adults with type 2 diabetes is beneficial. Among non-older adults, except for long-term reductions in myocardial infarction and mortality with metformin, using medications to achieve glycated hemoglobin levels less than 7% is associated with harms, including higher mortality rates. Tight control has been consistently shown to produce higher rates of hypoglycemia in older adults. Given the long timeframe to achieve theorized microvascular benefits of tight control, glycemic targets should reflect patient goals, health status, and life expectancy. Reasonable glycemic targets would be 7.0 – 7.5% in healthy older adults with long life expectancy, 7.5 – 8.0% in those with moderate comorbidity and a life expectancy < 1 0 years, and 8.0 – 9.0% in those with multiple morbidities and shorter life expectancy. [Emphasis added]

Sadly these articles aren't looking at dementia risk but at mortality. This topic appears to require a very deep dive for clarity, but I'm guessing that in the context of ketosis -- when hypoglycemia and insulin resistance aren't factors and ketones are providing the body with fuel -- having low HbA1c may not be a problem. It also looks like the microvascular benefits of lower HbA1c (good for our brains!) take a long while to be realized ... the lesson there being to safely get lower when younger.

Hopefully someone more versed in this will chime in.

[Julie G]

I've seen this paper kicking around the blogosphere for a while. I'm not sure what to think. My guess is that there's a wide swath of uncertainty around the small group of lowest hbA1c. From the paper:

Other biological processes, such as inflammation and liver function, may underlie the association between low hemoglobin A1c (<4.0%) and all-cause mortality

There's likely a key difference between those with chronic illness. who yield a low result, and those working on optimal health. If not, at 4.7, I could be in trouble .

[alangreenmd]

Hi Orangeblossom,

It's very hard to find anything in nature that doesn't have a U-shaped curve. People with lowest BMI have highest mortality in all studies.

Low HgA1c means chronic HYPOGLYCEMIA. There is nothing healthy about hypoglycemia and reflects major defect in fundamental homeostasis.
Major causes of fasting hypogylcemia include: severe liver disease, congestive heart failure, chronic renal insufficiency, starvation, certain large tumors, adrenal insufficiency, and most likely cause, excess alcohol intake.

Brain uses 25% of glucose, so if body not maintaining proper level of glucose for brain, you are not in good shape.

[Julie G]

On the other hand, those with higher (prediabetic) hbA1c levels often suffer from reactive hypoglycemia. My blood sugar is remarkable stable at 4.7 because I'm burning my own body fat- steady supply .

[Orangeblossom]

Maybe that is the case- it is that cause of the low HBAC1 makes the difference. So for some having another energy source would mean the low levels, whereas with others it could be caused by disease or lack of food...so what the source is could be causing the mortality risk depending on what it was...(or it might mean no risk if there was another source of energy)

In terms of an energy source for the brain, well it's not just glucose is it? taken from a conference talk -

"Ketones can provide up to 60% of the brain's energy requirements. Mild ketonaemia of 0.4 to 0.5mmol/l can contribute 5 to 10% of energy needs. Production of endogenous ketones during fasting is dependent on optimal blood glucose and insulin levels. Insulin directly inhibits ketogenesis. Low insulin directly initiates lipolysis, fatty acids go to the liver and are beta oxidised to ketone bodies which then enter the blood and are transported to the brain etc."

[circular]

taken from a conference talk -

"Ketones can provide up to 60% of the brain's energy requirements. Mild ketonaemia of 0.4 to 0.5mmol/l can contribute 5 to 10% of energy needs. Production of endogenous ketones during fasting is dependent on optimal blood glucose and insulin levels. Insulin directly inhibits ketogenesis. Low insulin directly initiates lipolysis, fatty acids go to the liver and are beta oxidised to ketone bodies which then enter the blood and are transported to the brain etc."

Hi Orangeblossom, I'd be interested in what conference this was and who the speaker was. Might want to hear more from it if there's a recording? If no recording I could find another venue for the same speaker?

[alangreenmd]

Hi Julia, In above studies, they include lots of people with chronic disease, alcoholism etc. in low HgA1cs.

In your case, HgA1c of 4.7% is perfect and reflects high level of physical activity and high level insulin sensitivity.

As a general rule, in order to understand the real story must look at insulin level, fasting blood glucose and HgA1c. 6% HgA1c with low insulin is OK, in contrast to 6 % HgA1c with high insulin, which shows insulin resistance and is bad, with same fasting blood sugar.
If don't get insulin levels, can't tell difference between glucose intolerance (OK) and insulin resistance (bad). Glucose intolerance seen during starvation.

[TheresaB]

My A1c went from 5.0 to is less than 4.2 (they don’t bother measuring below 4.2). The only thing that changed was I followed Dr Gundry’s dietary recommendations (a lot of low net carb veggies, moderate protein, good fats, no processed foods, etc). I’ve since wondered if it Is it possible to get too low of an average glucose level. Thus far, I haven’t found evidence to that. As long as the body is healthy, it will make the glucose as it needs it from protein or fat (gluconeogeneisis).

The REAL key is insulin. You don’t want it too high, nor do you want it too low. But since A1c is the measure of average glucose and that goes hand in hand with insulin, lower tends to be better, indicating greater insulin sensitivity.

From Dr Bredesen’s book, The End of Alzheimer’s, he says:

• Fasting glucose 70 to 90
  Fasting insulin 4.5 or lower
  Hemoglobin A1c of 5.6 or lower

[Orangeblossom]

taken from a conference talk -

"Ketones can provide up to 60% of the brain's energy requirements. Mild ketonaemia of 0.4 to 0.5mmol/l can contribute 5 to 10% of energy needs. Production of endogenous ketones during fasting is dependent on optimal blood glucose and insulin levels. Insulin directly inhibits ketogenesis. Low insulin directly initiates lipolysis, fatty acids go to the liver and are beta oxidised to ketone bodies which then enter the blood and are transported to the brain etc."

Hi Orangeblossom, I'd be interested in what conference this was and who the speaker was. Might want to hear more from it if there's a recording? If no recording I could find another venue for the same speaker?

Hi it was from a post on here, I will find the link for you. viewtopic.php?f=15&t=2515&hilit=ancestr ... r&start=10

RAND AKASHEH
Alzheimers disease: pathophysiology and nutritional implications: Role of glucose, lipids and ketone bodies in pathogenesis, prevention and management of AD, through mechanisms controlling nutrient transport in healthy and diseased brains

What causes an imbalance between protein formation and recycling? Associated factors for AD point to diabetes and increased insulin as a major risk factor.

The brain consumes 20 to 30% of the bodies energy. Substrates for the Krebs cycle are glucose (from food or gluconeogenesis), ketone bodies, lactate and MCTs.

In Alzheimers there is both reduced glucose uptake as well as cerebral insulin resistance with down regulation of receptors. There is proven ~20 to 25% decrease in glucose metabolism in the hippocampus in early AD and in other areas such as frontal, temporal and parietal lobes in later AD. Mechanisms include reduced expression of GLUT1 and 3, ineffective Krebs cycle and mitochondrial dysfunction (explains the maternal inheritance). This induces tau hyperphosphorylation which impairs neurotransmission.

It is critical to realise brain insulin resistance can occur in the absence of peripheral insulin resistance, obesity and diabetes.

Ketones can provide up to 60% of the brain's energy requirements. Mild ketonaemia of 0.4 to 0.5mmol/l can contribute 5 to 10% of energy needs. Production of endogenous ketones during fasting is dependent on optimal blood glucose and insulin levels. Insulin directly inhibits ketogenesis. Low insulin directly initiates lipolysis, fatty acids go to the liver and are beta oxidised to ketone bodies which then enter the blood and are transported to the brain etc.

She stressed that a high fat low carb diet may not necessarily induce ketosis if insulin resistance is present. This needs to be addressed first by weight loss, exercise, fasting etc

She also discussed the role of IDE (insulin degrading enzyme) which has a role in degrading many other proteins other than insulin , especially relevant is that it degrades amyloid. High circulating insulin will preferentially bind to it so there is less available to degrade amyloid.