Monday, September 12, 2011

Fasting blood glucose of 83 mg/dl and heart disease: Fact and fiction

If you are interested in the connection between blood glucose control and heart disease, you have probably done your homework. This is a scary connection, and sometimes the information on the Internetz make people even more scared. You have probably seen something to this effect mentioned:
Heart disease risk increases in a linear fashion as fasting blood glucose rises beyond 83 mg/dl.
In fact, I have seen this many times, including on some very respectable blogs. I suspect it started with one blogger, and then got repeated over and over again by others; sometimes things become “true” through repetition. Frequently the reference cited is a study by Brunner and colleagues, published in Diabetes Care in 2006. I doubt very much the bloggers in question actually read this article. Sometimes a study by Coutinho and colleagues is also cited, but this latter study is actually a meta-analysis.

So I decided to take a look at the Brunner and colleagues study. It covers, among other things, the relationship between cardiovascular disease (they use the acronym CHD for this), and 2-hour blood glucose levels after a 50-g oral glucose tolerance test (OGTT). They tested thousands of men at one point in time, and then followed them for over 30 years, which is really impressive. The graph below shows the relationship between CHD and blood glucose in mmol/l. Here is a calculator to convert the values to mg/dl.

The authors note in the limitations section that: “Fasting glucose was not measured.” So these results have nothing to do with fasting glucose, as we are led to believe when we see this study cited on the web. Also, on the abstract, the authors say that there is “no evidence of nonlinearity”, but in the results section they say that the data provides “evidence of a nonlinear relationship”. The relationship sure looks nonlinear to me. I tried to approximate it manually below.

Note that CHD mortality really goes up more clearly after a glucose level of 5.5 mmol/l (100 mg/dl). But it also varies significantly more widely after that level; the magnitudes of the error bars reflect that. Also, you can see that at around 6.7 mmol/l (121 mg/dl), CHD mortality is on average about the same as at 5.5 mmol/l (100 mg/dl) and 3.5 mmol/l (63 mg/dl). This last level suggests an abnormally high insulin response, bringing blood glucose levels down too much at the 2-hour mark – i.e., reactive hypoglycemia, which the study completely ignores.

These findings are consistent with the somewhat chaotic nature of blood glucose variations in normoglycemic individuals, and also with evidence suggesting that average blood glucose levels go up with age in a J-curve fashion even in long-lived individuals.

We also know that traits vary along a bell curve for any population of individuals. Research results are often reported as averages, but the average individual does not exist. The average individual is an abstraction, and you are not it. Glucose metabolism is a complex trait, which is influenced by many factors. This is why there is so much variation in mortality for different glucose levels, as indicated by the magnitudes of the error bars.

In any event, these findings are clearly inconsistent with the statement that "heart disease risk increases in a linear fashion as fasting blood glucose rises beyond 83 mg/dl". The authors even state early in the article that another study based on the same dataset, to which theirs was a follow-up, suggested that:
…. [CHD was associated with levels above] a postload glucose of 5.3 mmol/l [95 mg/dl], but below this level the degree of glycemia was not associated with coronary risk.
Now, exaggerating the facts, to the point of creating fictitious results, may have a positive effect. It may scare people enough that they will actually check their blood glucose levels. Perhaps people will remove certain foods like doughnuts and jelly beans from their diets, or at least reduce their consumption dramatically. However, many people may find themselves with higher fasting blood glucose levels, even after removing those foods from their diets, as their bodies try to adapt to lower circulating insulin levels. Some may see higher levels for doing other things that are likely to improve their health in the long term. Others may see higher levels as they get older.

Many of the complications from diabetes, including heart disease, stem from poor glucose control. But it seems increasingly clear that blood glucose control does not have to be perfect to keep those complications at bay. For most people, blood glucose levels can be maintained within a certain range with the proper diet and lifestyle. You may be looking at a long life if you catch the problem early, even if your blood glucose is not always at 83 mg/dl (4.6 mmol/l). More on this on my next post.


MM said...

If these numbers aren't based on fasting blood glucose, what are they based on?

Thanks for debunking this. I always thought it sounded a little fishy.

Ned Kock said...

Hi MM. They are 2-hour blood glucose levels after a 50-g oral glucose tolerance test.

Chris Kresser said...

I am the blogger that made that statement. I think it was in my articles on "Why your 'normal' fasting glucose isn't normal."

Thanks for pointing out the flaws in the study and how I interpreted it. I wrote that article before I had started seeing patients. Since then, I've tested over 300 people's blood sugar, and have seen a fairly wide range of fasting values even in people without obvious blood sugar issues.

I've also learned that getting an accurate read on blood sugar is difficult, because none of the testing methods are perfect. Fasting glucose just tells you what was happening that day, and perhaps the day before. A1c assumes the same 90-day turnover rate of red blood cells in all people, which we now know is inaccurate. And OGTT is based on ingesting a 50g bolus of glucose, which hardly anyone does.

It's really like putting pieces of a puzzle together.

I need to go back and change that article.

Chris Kresser

David Isaak said...

Nice one, Ned.

As a side note, I've heard many times from low-carbers that the OGTT gives highly misleading results for people on low-carb diets. For many of them, 50 g glucose is equivalent ot an entire day's intake, and their systems aren't adapted to a sugar spike of that magnitude.

A number of low-carbers recommend "carbing up" a few days before if you know you have a OGTT coming, just to get the body system prepped--otherwise your doctor may march into the room and inform you that you have prediabetes.

Ned Kock said...

Hi David. I’ve heard that one too, many times. It may be true, and I wonder what the underlying reason is, from a hormonal/biochemistry perspective.

If one has more FFAs and ketones in circulation, you’d expect peripheral benign insulin resistance to set in after a while. We know that elevated growth hormone levels cause that.

Ned Kock said...

Hi Chris. Have you thought about measuring the GH levels of those clients who have higher than expected blood glucose levels and no signs of the metabolic syndrome?

Chris Kresser said...

I haven't done that yet. I do test for iron levels, because iron overload can decrease insulin sensitivity and glucose tolerance and is very common in men.

I'm not sure what the clinical value (for me) of knowing they have decreased GH would be, because I pretty much advise anyone that is overweight or IR to do glycogen-depleting exercise and do IF.

Yasin said...

Another great post Ned. Excited for your next post as I am curious as to what range you would consider "healthy" from your review of the literature.

Chris, it's nice to see a practitioner willing to re-challenge ideas in face of new or different evidence.

Ned Kock said...

Hi Chris. The value of measuring GH levels would be to see if they increased in a way that was correlated with blood glucose level increases, should the latter happen.

This would suggest a natural adaptation process, similar to what happens in GH therapy, putting the clients at ease. Getting one’s metabolism “fixed” is as much a mental process as it is a physiological one.

Ned Kock said...

Hi Yasin, thanks.

Helen said...
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Helen said...

*Thank you.*

I've heard this argument from bloggers other than Chris Kresser.

In any case, the blogger I'm thinking of (not Chris) also implies that you are in serious trouble if your BG *ever* exceeds 100mg/dl after a meal. He also tends to be vague on when to test. Once, when asked what values to expect when testing, he gave a link to a resource page on his web site, which pointed to increased heart disease when BG exceeded 100mg/dl @ two hours post-prandial. The studies didn't show an increased risk at one hour. A respected diabetes blogger (Jenny Ruhl) states that she hasn't seen evidence that high BG at 1/2 hour are significant to health.

I'm not saying that a large spike at one hour isn't concerning (particularly in excess of 165mg/dl - Jenny would say 140mg/dl), but the most documented risk factors seem to come into play with elevated BG at two hours.

I might be biased in what I want to believe, since I have high fasting blood glucose, and early post-prandial spikes, but tend to get to 100mg/dl or below at two hours pp in most cases.

In any case, I do think there is some unnecessary fear-mongering out there in our neck of the blogosphere.

The flip side of that is over-acceptance of too-high glucose by mainstream medicine. The alarm bells often aren't sounded early enough for many people to catch a situation before they become diabetic.

Ned Kock said...
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Ned Kock said...

Hi Helen. Yes, the issue of scaring people with fiction versus making them overconfident is always a problematic one.

One thing seems to be almost certain at this point: glycogen-depleting exercise (e.g., weight-training, sprints) is healthy for diabetics in the long run, even thought it will invariably lead to hyperglycemia (BG > 180 mg/dl) in diabetics during the exercise session.

This is a blow to any theory arguing that your BG must be always below a certain relatively low level like 140 mg/dl. Such a theory cannot be true and still be compatible with the benefits of glycogen-depleting exercise.

David Isaak said...

"...glycogen-depleting exercise (e.g., weight-training, sprints) is healthy for diabetics in the long run, even thought it will invariably lead to hyperglycemia (BG > 180 mg/dl) in diabetics during the exercise session."

Interesting. I wasn't aware of that. Of course, I don't know what BG of normoglycemics is during exercise.

Could you elaborate?

Ned Kock said...

Hi David. The post below has a graph showing what happens with young normoglycemics:

David Isaak said...

Fascinating. I guess that blood glucose is a lot like blood pressure--you want it to be able to go way up. You just don't to stay there when the stressor is removed.

I browsed around the web a bit after reading your post. There's actually a website about diabetics engaging in sports:

Reading the article on marathoning by a Type I diabetic made me very happy that my body handles all of ths for me automatically. Trying to balance BG needs and insulin while exercising is a logistical nightmare.

All in all, our bodies are pretty clever regulatory systems.

Ned Kock said...

Thanks for the link David. As on many other similar forums, with many folks with T1D, much of the advice there is on how to avoid hypoglycemia.

Hyperglycemia is not mentioned often.