Having lived a great deal of my life in Norfolk, I’ve always rather liked the EPIC Norfolk publications. This was the first paper that I found which demonstrated, at the population level, that HbA1c is an excellent marker for your risk of both CVD and all cause mortality.
HbA1c is one of the most simple biomarkers to manipulate. If there was one single biomarker which you might want to modify, HbA1c is the one.
In Norfolk, people don’t.
Here people generally eat CIAB, more politely known as the UK version of the SAD or a mixed diet.
I doubt very much that anyone eats far enough away from “normal” or “unremarkable” macronutrient ratios that it has any significant effect on the distribution of HbA1c in the population. So, if you take a large group of people and set them free to eat whatever they want, HbA1c is probably a surrogate for mitochondrial health, particularly the mitochondria in adipocytes but more probably those throughout the body.
Nobody doubts that hyperglycaemia is damaging. Hyperinsulinaemia appears to problematic in its own right too. But my impression is that whether you succumb to a disease which is the result of hyperglycaemia directly or due to hyperinsulinaemia, this is just the label. The core problem is the underlying failure of mitochondrial function which signifies to a cell that it’s time to shut up shop. How this shows macroscopically, at the whole organism level, is probably up to a host of factors which I find of limited interest.
Sooooooo. Let’s be very specific: I consider, in the general population, that the linear positive relationship between HbA1c and all cause mortality is a reflection of failing mitochondrial health.
HbA1c is also the easiest of biomarkers to fudge, adjust or fake, call it what you will.
While diabetologists agonise over the inexorable progression of diabetes and wet their knickers at clinically insignificant drops in HbA1c on a calorie restricted mixed diet, those of us who eat LC are well aware that the 5% club is wide open to diabetics and the 4% club is not difficult for those of us who learned LC before mitochondrial damage became widespread. Most, although perhaps not all, people can drop their HbA1c to physiological levels with carbohydrate restriction, possibly with modest supplementation using metformin if they are significantly injured.
Dropping your HbA1c is easy. Very easy.
I have been thinking about this for a long time.
The really difficult question is whether an HbA1c of 4.4% achieved through the strict avoidance of post prandial hyperglycaemia is quite the same as an HbA1c of 4.4% achieved by a random chance combination of accidentally reasonable food choices, a functional pancreas, functional muscles, reasonable parental/intrauterine environment and good luck. Plus anything else you care to think of.
The LC eater is producing an effect on HbA1c which has never been investigated on a population basis, certainly not using modern, insulin resistant people who choose to normalise their blood glucose levels through diet. Whether it is as good for health and/or longevity as achieving it accidentally remains to be seen. No one need ask where my suspicions lie, but there are no hard data. There is absolutely no reason to doubt that being insulin resistant while eating A MIXED DIET indicates that you are in trouble, mitochondrially speaking. Sidestepping this with low carbohydrate eating will undoubtedly reduce your risk of those diseases which are a direct result of the hyperglycaemia and hyperinsulinaemia and which become inevitable on a mixed diet if you are insulin resistant. My own feeling is that this step is vital. I also suspect that some degree of reparation in mitochondrial health might be possible with long term near or frankly ketogenic eating.
OK, enough on the EPIC findings and my thoughts about adjusting HbA1c.
The next big step is to leave Norfolk’s EPIC beauty and wander over to the USA and look at the catastrophic association of a low HbA1c with death. As everyone undoubtedly knows, this link came to me from the exchange between Paul Jaminet and Ron Rosedale over safe starches. I was unaware of the study until Paul brought it up as a foil to the EPIC Norfolk findings.
It too, is a nice observational study.
I have to look at the data here in exactly the same way as I have looked at the data from EPIC. What might it mean? These are observational studies, their use is to generate hypotheses. What is the Hyperlipid view of an HbA1c of 2.8% (that is not a typo) on a mixed USA diet?
The easiest question to answer is whether this might be a surrogate for exceptional mitochondrial health. If you assume that the formula for conversion of HbA1c to average blood glucose levels holds true at the 2.8% level of HbA1c (which it obviously doesn’t), it would represent an average blood glucose of 1.0mmol/l. The lady would be dead. So, before we make idiotic assumptions about average blood glucose levels and mitochondrial health here, we had better think very carefully about what, exactly, a very low HbA1c might really mean. We can say for a start that it is not a simple reflection of glycaemia.
By far the most plausible explanation is not that the red blood cells have been exposed to 1.0mmol/l for the last three months, it’s more likely that these red cells have been exposed to a higher level of glucose, possibly somewhat physiological, for a significantly shorter period of time i.e. the red blood cells are young. Always young. They don’t hang around for long enough to become old and glycated before they are lost. Obviously the study group was well aware of this possibility and corrected for it as best they could.
The lowest HbA1c group had the lowest haemoglobin count, the highest red cell width variability (suggestive of regenerative anaemia) and the highest red blood cell volume (each RBC having relatively little haemoglobin). If you don’t think this group contained some seriously anaemic people you’re probably mistaken. Correcting for red blood cell variables in model 2d of Table 2 gave the bottom limit of the 95% confidence intervals closest to 1.0 of all of the adjusted low HbA1c models.
A quick glance at the ferritin levels, paradoxically, shows that these folks also appear to have iron overload. This may or may not be real as the group also contains 11% people sero positive for hepatitis C virus. As ferritin is an acute phase protein its elevation in a hepatitis C patient may be related to inflammation rather than to iron overload. Correcting for iron based parameters (model 2e) resulted in a worse "higher lowest" limit of confidence intervals than the basic correction for age, ethnicity and sex. You have to wonder if this might be due to an incorrect assumption about ferritin levels.
Of course there were four times as many hep C carriers in the low HbA1c group as the reference group. Model 2f tried to correct for this but I doubt they were able to control for those people using iv heroin (glycaemia neutral) vs those on iv crack vs those on oral stimulants (glycaemia lowering). Anorexia and hypoglycaemia are not uncommon under extended periods of recreational stimulant use. This information seems unlikely to be available to allow adjustment in the NHANES III models.
So I see two studies and each generates a different hypothesis. EPIC suggests that progressive mitochondrial failure on a mixed diet shows as raised HbA1c. The second, from NHANES III, is that sub-physiological HbA1c readings correlate to changes other than physiological glycaemia. Many of these changes appear to bad news, and HbA1c here is the messenger, just as it is in Norfolk.
Using this sort of observational data to convince yourself to increase your starch intake may be a mistake. Avoiding iv drug use and the metabolic consequences there-of might be a better approach.
If anyone can achieve an HbA1c of 2.8% by avoiding starch consumption I'll plaster it all over this post as an edit.
Above all of this, in the realms of sensible living, is the fascinating question of whether an HbA1c of 4.4% achieved by VLC eating has the same (positive) health implications as an HbA1c of 4.4% on a mixed diet.
BTW the EPIC researchers had a look at low HbA1c in Norfolk. Looks like speed is not the preferred recreational drug here. This fits with my experience dealing with the general population where I live.