Keep the Leptinade flowing! I'm going to die from my glucose anyway ...

A few general thoughts on this whole "safe starches" tangent into Ron  "Everyone's a Diabetic" Rosedale's contentions.  I was prompted to look into many of the claims of Rosedale by a short conversation I had with him over at PaleoHacks that can be found scrolling down to his responses here.  When one goes and reads the Facebook links in the root post, it is clear that Rosedale's views are pretty extreme as regards blood glucose levels, diabetes, etc.  It comes down, really, to viewing all blood glucose, leading to any level of glycation, as harmful.  Basically through Rosedale-colored glasses we see circulating glucose as always harmful and to be kept minimal both in circulation and as cellular fuel as much as possible for optimal health.  He also advocates getting virtually no glucose from your diet, relying, instead on your liver for all glucose needs.   Glycation debilitates, deteriorates and ultimately kills you, and in Rosedale's opinion, there's no "safe" level of glucose and its insidious glycation that causes no harm.  

As such, Jimmy Moore published a rebuttal to the rebuttal of sorts by Rosedale in response to Paul Jaminet of Perfect Health Diet.  Now, I think it's probably known to most of my readers that Paul is perfectly capable of responding eloquently to this, and I most certainly do not want to be seen as stepping on any toes.  But I think Jimmy's massive data dump blog posts -- liberally speckled with various uncalled for responses from LC luminaries -- deserve as many dismantlings as bloggers out there are willing to put up.  Law of numbers and all that, and hopefully some of this nonsense can be dispelled before we layer even more myths on a list that is already too long in low carb circles.

And so, with my previous post, I decided to focus on this notion that there is no such thing as a safe starch because there's no such thing as a safe glucose level, and look at some of the references Rosedale provided to make the case that this is "clearly" so.

Next up:  Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study

Rosedale's excerpt:

“Results During follow-up of 18,406 non-diabetic men, 13,116 deaths occurred (1,189 by stroke).Plots of stroke mortality rates versus [post challenge of 50 gms] blood glucose identified an upward inflection in risk of death from stroke at about 4.6 mmol/l [82 mg/dl]. This upward inflection in risk could be adequately described using a single linear term above this threshold. Conclusions/interpretation; An incremental elevation in stroke mortality rates occurs with increasing post-challenge blood glucose.”

Sounds daunting no?  Frankly I'm surprised Rosedale doesn't take megadoses of metformin or drink heavily to reduce his liver glucose production after reading that!  Let's take a closer look, shall we?  First some additional excerpts:

First, that 82 mg/dL sounds awfully daunting as to some apparent inflection point for stroke risk!  Yikes!!  But:

One final potential problem is that, as described, the post-challenge blood glucose test used in the Whitehall study at baseline in the 1960s is non-standard in comparison to present day protocols. The characteristics of this test explain why blood glucose levels found at baseline in the present study seem lower than expected, for instead of the 75 g glucose challenge employed today, a 50 g challenge was used.

Apparently even the authors didn't recognize another reason the levels seemed so low, though they did mention it in a cautionary statement about interpreting results.

However, to interpret our findings, it is necessary to point out that the blood glucose test was non-standard in several respects: (1) it was post-challenge; (2) the challenge itself (50 g) was lower than has been used elsewhere (75 g); (3) capillary rather than venous was drawn; and (4) whole blood rather than plasma was assayed.

That last one caught my eye, so I set out to see what the differences might be between whole blood vs. plasma levels of glucose.  This led me to find Differences in Glucose Determinations Obtained From Plasma or Whole Blood.  At right is the regression line generated in that paper for plasma glucose vs. whole blood.  

82 mg/dL whole blood is actually around 100 mg/dL in plasma

Let's put this together now, because as we all know, context is everything.  Somehow that alarming 2 hr post glucose level where stroke mortality risk "takes off" doesn't sound as bad.  A current standard OGTT is 75g glucose, which is 50% more than the 50g challenge administered in this study.  The 2-hour plasma level is really around 100 mg/dL, and while we wouldn't expect a comparable value to be 50% higher, it would likely be somewhat higher, particularly in the population displaying some degree of IGT.  

Before we look at the data and analysis, let's look at how they broke up the population

The present analyses are therefore based on 18,406 men (17,724 for whom data were complete, 682 for whom data values on missing continuous covariates were imputed). Preliminary analyses showed that the main increase in stroke mortality rates was above the 90th percentile of blood glucose distribution. We therefore partitioned the population into three equally sized groups below this point and four, progressively smaller, groups above it, enabling any differences in mortality rates either side of this inflection to be detected.

Keep this in mind here when you view the data below.  The left three columns contain 90% of the men with 2hr50gWholeBG's ranging from 2.5 to 4.94 mmol -- which corresponds to PlasmaG's of  54 to 107 mg/dL.

So let's see here.  Within the bottom 90% -- one might call these not just the "normal" group but presumably a decent amount of what glucophobes would put somewhere on the continuum of "diabetic" -- 2hr50gWBG levels almost doubled.  And yet there was NO difference in all-cause mortality -- either by mortality rate or any of the three models.  Further, although not likely significant, the stroke mortality rates for the middle third of this group were ever so slightly higher than for the lower or upper third.    Rosedale's scientific "shock" is a "flatline" folks. No safe increase in postprandial blood glucose?  Really?  Even if you go up the next 4% -- from the 90th to the 94th percentile, topping off at an equivalent of 115 mg/dL plasma -- we see no significant increase in all-cause mortality.  I suppose, though, that if one has a preference in their mode of death, and dying of a stroke is not it, there's a smidgen of  cause for concern.

The ultimate conclusions were:

A 1 mmol/l increase in blood glucose after this point [4.6 mmol WBG = 100 mg/dL PG] was associated with a 27% increase in risk of death from stroke (hazard ratio 1.27, 95% CI 1.14–1.42). This increase in risk was partially attenuated by adjustment for covariates (1.17, 1.04–1.31) but remained statistically significant at conventional levels. Similar observations were made when all-cause mortality was the outcome of interest, although the magnitude of the association with blood glucose was somewhat lower.

Let's really put this in context folks and for that I need another graphic.  Presuming a normal distribution for glucose tolerance, at right I've identified the cut-off's for each of the columns in the data table from the study.   If the number 90% is not enough to grasp the proportion of the population we're talking about, then the first thing to note would be the size of the areas of the blue and green portions combined in which both stroke and all-cause mortality were virtually identical.   I'm not really sure where they get the 4.6 -- center value of section III -- as where it takes off, but I've approximated this line and the 4.6 + 1 mmol line (in orange section V) as blue lines, to show just how relatively ridiculous this risk assessment is. What this says is that if someone's response to a glucose challenge goes from being in about the 75th percentile to about the 95th percentile, their risk of dying of a stroke increases 27% (less if other factors are accounted for) and risk of dying of all cause even less still.  Pretty bold and alarming, no?  

Now, please enlighten me if I'm way off here, but this study began from 1967-1970 in London-based male civil servants ranging from 40-69 years of age.  Was there some parallel Minnesota like experiment going on at the same time such that we are to believe that these seemingly lower glucose levels were due to abstaining from starches?  I would think not!  Whole grain propaganda or not, these men were likely consuming a fair amount of starch, wheat at that, in their diets.  And yet there were no perceptible differences through the 90th percentile.  

Bottom line, this study does nothing to point to some "clear" evidence that postprandial glucose levels of 140 mg/dL are in any way, shape or form harmful.  This study looked at the postprandial glucose levels after two hours from a standardized 50g challenge.   If we're going to use PHD recommendations, spread out over three meals, this would be the starch dose per meal.  Even if your BG doesn't fall back below whatever the values are from this study, does that mean the glucose excursion is harmful?  No.  It only means that you may be insulin resistant to a degree that puts you at risk and you can assess that risk with such a test.  It does not mean the glucose levels themselves are harmful, indeed if they were not benign the human race would likely have been wiped off the planet by now.  Well ... all except for the Inuit I suppose.

This is worth repeating:  An elevated 2 hour glucose level result from an OGTT indicates impaired glucose disposal -- the mechanism of which is some underlying metabolic dysfunction.  This does not mean that a glucose level of that magnitude is risky or detrimental, or somehow causes damage.  

Rosedale has the 'splaining to do here.  

To be continued.