Monday, September 19, 2011

Being glucose intolerant may make you live only to be 96, if you would otherwise live to be 100

This comes also from the widely cited Brunner and colleagues study, published in Diabetes Care in 2006. They defined a person as glucose intolerant if he or she had a blood glucose level of 5.3-11 mmol/l after a 2-h post–50-g oral glucose tolerance test. For those using the other measurement system, like us here in the USA, that is a blood glucose level of approximately 95-198 mg/dl.

Quite a range, eh!? This covers the high end of normoglycemia, as well as pre- to full-blown type 2 diabetes.

In this investigation, called the Whitehall Study, 18,403 nonindustrial London-based male civil servants aged 40 to 64 years were examined between September 1967 and January 1970. These folks were then followed for over 30 years, based on the National Health Service Central Registry; essentially to find out whether they had died, and of what. During this period, there were 11,426 deaths from all causes; with 5,497 due to cardiovascular disease (48.1%) and 3,240 due to cancer (28.4%).

The graph below shows the age-adjusted survival rates against time after diagnosis. Presumably the N values refer to the individuals in the glucose intolerant (GI) and type 2 diabetic (T2DM) groups that were alive at the end of the monitoring period. This does not apply to the normoglycemic N value; this value seems to refer to the number of normoglycemic folks alive after the divergence point (5-10 years from diagnosis).


Note by the authors: “Survival by baseline glucose tolerance status diverged after 5-10 years of follow-up. Median survival differed by 4 years between the normoglycemic and glucose intolerant groups and was 10 years less in the diabetic compared with the glucose intolerant group.”

That is, it took between 5 and 10 years of high blood glucose levels for any effect on mortality to be noticed. One would expect at least some of the diagnosed folks to have done something about their blood glucose levels; a confounder that was not properly controlled for in this study, as far as I can tell. The glucose intolerant folks ended up living 4 years less than the normoglycemics, and 10 years more than the diabetics.

One implication of this article is that perhaps you should not worry too much if you experience a temporary increase in blood glucose levels due to compensatory adaptation to healthy changes in diet and lifestyle, such as elevated growth hormone levels. It seems unlikely that such temporary increase in blood glucose levels, even if lasting as much as 1 year, will lead to permanent damage to cells involved in glucose metabolism like the beta cells in the pancreas.

Another implication is that being diagnosed as pre-diabetic or diabetic is not a death sentence, as some people seem to take such diagnoses at first. Many of the folks in this study who decided to do something about their health following an adverse diagnosis probably followed the traditional advice for the treatment of pre-diabetes and diabetes, which likely made their health worse. (See Jeff O’Connell’s book Sugar Nation for a detailed discussion of what that advice entails.) And still, not everyone progressed from pre-diabetes to full-blow diabetes. Probably fewer refined foods available helped, but this does not fully explain the lack of progression to full-blow diabetes.

It is important to note that this study was conducted in the late 1960s. Biosynthetic insulin was developed in the 1970s using recombinant DNA techniques, and was thus largely unavailable to the participants of this study. Other treatment options were also largely unavailable. Arguably the most influential book on low carbohydrate dieting, by Dr. Atkins, was published in the early 1970s. The targeted use of low carbohydrate dieting for blood glucose control in diabetics was not widely promoted until the 1980s, and even today it is not adopted by mainstream diabetes doctors. To this I should add that, at least anecdotally and from living in an area where diabetes is an epidemic (South Texas), those people who carefully control their blood sugars after type 2 diabetes diagnoses, in many cases with the help of drugs, seem to see marked and sustained health improvements.

Finally, an interesting implication of this study is that glucose intolerance, as defined in the article, would probably not do much to change an outside observer’s perception of a long-living population. That is, if you take a population whose individuals are predisposed to live long lives, with many naturally becoming centenarians, they will likely still be living long lives even if glucose intolerance is rampant. Without carefully conducted glucose tolerance tests, an outside observer may conclude that a damaging diet is actually healthy by still finding many long-living individuals in a population consuming that diet.

26 comments:

Gretchen said...

1. Annecdotal: My mother was Dx'd with type 2 diabetes at the age of 65. She died from heart disease at almost 98 and didn't take medication or follow a strict LC diet.

2. Bill Polansky says, "Diabetes causes nothing." It's *uncontrolled diabetes* that is a problem. See

http://www.healthcentral.com/diabetes/c/5068/140690/complications

3. It's known that complications take about 10 years to show up. The problem with people with type 2 diabetes is that most have had the disease for about 10 years before they realize they have it, so they have complications when Dx'd. These are the microvascular complications like neuropathy. But they probably also have macrovascular complications like plaque.

4. Blood glucose levels are a continuum between low normal and clearly diabetic. Any cutoff between "normal" and "glucose intolerant" is artificial and can change with current thinking.

My feeling is to be aware of problems with chronic high blood glucose levels but not to panic. Many people live for years with diabetes. Joslin has patients who have had type 1 for 50 and even 60 years.

Knowing you have a tendency to high glucose levels may be just what you need to nudge you into eating healthier foods so you live longer than your neighbor who doesn't.

js290 said...

What does "Type 2 diabetic" mean exactly? Beta cell damage and no longer capable of producing insulin?

Beth@WeightMaven said...

Hmmm. Sure makes me wonder how "Wheat Belly" Davis' prescription to keep postprandrial BG under 140 fits in. He's essentially saying everyone needs to be on a nearly ketogenic diet. I'm not ready to go there just yet!

M & M said...

translate polisch-english
http://tinyurl.com/3p4p77k

Ladies and Gentlemen,
I wanted to give you information on the role of glucose in people taking Nutrition
Optimal (®), because there are different views here, which have nothing in common with reality.

Well, at the optimal normal blood glucose level is higher than in other people using other models of nutrition and averages 110-140 mg%. And this value is correct sugar levels. Administration of glucose, for example, the performance of the so-called. attempts to sugar curve, increases in glucose levels, which slowly decreases the level of what doctors interpret as pathological curve of corn and try to convince the test that their sugar curve indicates the presence of type II diabetes.

For each person applying Optimum Nutrition (®) called. Sugar is an attempt to "pathological" because the body is not adapted to the rapid combustion or processing large amounts of glucose,
especially given rapidly. Since the optimal carbohydrate eating enough, their bodies are adapted to supply a small amount of carbohydrates.

Of the three gram molecule arises a glucose fatty acid gram molecule
in the chain, for example, a complex of eighteen carbons and eight gram molecule oxygen. This oxygen is used for internal respiration. Formula reaction:

3C6H12O6 --> C18H36O2 + 8O2

3 mole weighs 540 g of glucose, which is formed from 284 g of fatty acid stearic
and 256 g of oxygen, that is -

with 100 g of glucose on 53g of processed fatty acid, stearic
formed 47, 4g of oxygen, or about 33 liters of oxygen (O2).

Helen said...

I do wonder if the stress I've had about my highish glucose levels are more damaging than the highish glucose levels themselves. Especially since it was doubtful that I was on a "damaging diet" to begin with, and low-carb and low-fat diets and a 30 lb weight loss (from 155 to 125) brought the same 0.4 reduction in my A1c (6.4 to 6.0) and no more, and I was an A student in following that low-carb diet.

I'm sure this is vastly different from many other people's experiences - for instance, my father-in-law went from an A1c of 12 to one of 5.7 mainly by taking Metformin (which did nothing for me).

He falls into a "classic Type II diabetes" profile, while I don't.

In any case, your post makes a good points - and helps me put my stress about my BG in perspective.

And, like you say, compromised glucose control does not always represent the same systemic stuff going on - different causes come with different effects - poor outcomes related to high blood sugars surely have a good deal with the sugars themselves, but also have to do with the things that typically cause them and go along with them - like hypertension and high triglycerides.

For instance, I think I may have a monogenic form of diabetes. (Of interest: "Clues to finding further causes for monogenic diabetes" http://www.sciencedaily.com/releases/2011/09/110921074734.htm)

In one form (MODY 2), despite having A1c's between 6.0 and 7.0, patients don't apparently have increased cardiovascular or microvascular risks. Triglycerides tend to be low, and obesity is not common. (Thought this might be me, as I fit the profile, but genes say no.)

gwarm said...

One thing about the glucose tolerance test is the 'physiological insulin resistance' of those who eat low-carb to consider. Links to a post on hyper-lipid:

http://www.lowcarbconversations.com/344/22-barbara-rose-dean-dwyer-paleo-guy-weston-price-gal-discuss-body-image-more/#comment-306963040

Hyperlipid: "However, while muscles are in "refusal mode" for glucose the least input, from food or gluconeogenesis, will rapidly spike blood glucose out of all proportion. This is fine if you stick to LC in your eating. It also means that if you take an oral glucose tolerance test you will fail and be labelled diabetic. In fact, even a single high fat meal can do this, extending insulin resistance in to the next day. Here's a reference for this.

The general opinion in LC circles is that you need 150g of carbohydrate per day for three days before an oral glucose tolerance test [link].

I did this carb loading thing, then performed my own OGTT. It came out very normal except for mild reactive hypoglycaemia. "
--
Now that I eat higher carb (try 150g/day for 3 days first) I have noticed sweet potatoes (cooked sweet potato w/o skin... and you can eat w/ tsp of cinnamon and the fructose in the potato will lower the glycemic impact too) don't make me hypoglycemic anymore and now I eat 2-3 potatoes a day but I will have to try it with white rice (which has no natural nutrients, fiber/prebiotic and is higher glycemic) to see if I'm good with that "safe starch" (but white rice is full of undesirable fortified b vitamins/folic-acid).

Ned Kock said...

Hi Gretchen, thanks for sharing and good points. Anecdotal, but powerful! What has your mother eaten before and after the diagnosis?

Ned Kock said...

Hi js290. T2D is generally associated with impaired beta cell function, but still some insulin production.

Ned Kock said...

Hi Beth. I think that the 140 rule is a good one. I tend to follow it myself.

If you are normoglycemic and older than 40 that will usually mean not eating most industrial carb-rich foods, particularly the ones made from refined wheat.

Postprandial glucose levels in response to the same glucose challenge tend to go up with age in most people, even the very long lived.

Usually eating natural carb-rich foods, such as fruits, as desserts to meals based on protein and/or fat will also lead to lower postprandial blood glucose levels.

Ned Kock said...

Hi Helen. I am becoming increasingly convinced that diabetes is a compensatory adaptation to protect us from something – the most obvious candidate is hypoglycemia.

That would be an evolved response in polygenic diabetes, suggested by the very high prevalence of this condition in modern populations. Too high for it not to have been evolved.

But I am not sure it would be an evolved response in monogenic diabetes, which is a rare type of diabetes.

Ned Kock said...

Btw, Helen, thanks for the link. Very interesting.

Ned Kock said...

Hi gwarm. Yes, I hear a lot about that carb-loading effect, but haven’t seen a paper discussing it yet.

Keep in mind that the carb-loading may mask reactive hypoglycemia somewhat, making it less accentuated.

And if there is something that is worth catching early is reactive hypoglycemia. The path to hyperglycemia, in the context of T2D, is paved with low blood glucose levels …

gwarm said...

One thing to consider about low-carb diets is this 'physiological insulin resistance.' (linked in that hyperlipid post).

And in the comments of hyperlipid: "I've noticed that since I've reduced my carb intake, eating a high-carb meal kicks my butt. I feel like... my blood glucose is through the roof and all my proteins are being glycated!! Seriously, I feel warm all over and tired as if I were having a systemic inflammatory response. Although it may just be my overactive imagination."
-
What happens when cortisol goes up? example: cortisol goes up from bad sleep (or stressors that cannot be eliminated) leading to->dumping glucose into bloodstream and higher A1C's, AGEs etc (?)

Lerner said...

quoting Gretchen: "It's known that complications take about 10 years to show up."

This is echoed just now at EASD 2011, re the Hoorn Study:

"Glucose disturbances appear years before diabetes diagnosis"

http://www.theheart.org/article/1280851.do

Lerner said...

@js290: the diagnostic criteria for Type II, from WHO and ADA = fasting blood glucose >126, or OGTT >200 or A1c > 6.5

Lerner said...

yet as things always get complicated, the ACCORD study showed that aggressive lowering of A1c = more death, not less.

Also, though I'd always heard that glycation of proteins is irreversible, it turns out that N-acetylcarnosine eyedrops are used in prevention and even reversal of glycation in cataracts:

http://www.ncbi.nlm.nih.gov/pubmed/19487926

What other areas have treatments to reverse glycation?

Ned Kock said...

Hi gwarm. IR is a whole-body measure, but many tissues may present different degrees of IR at different points in time, differentially contributing to the whole-body IR effect.

For example, elevated GH levels tend to lead to whole-body IR in adults, apparently because the liver does not become insulin sensitive at the same speed as muscle tissue becomes IR. The latter is generally a good short-term adaptation – i.e., muscle running more on FFAs and less on glucose is generally a good thing.

Eventually the liver seems to catch up, a long-term compensatory adaptation:

http://bit.ly/jh9wcm

What can lead to elevated GH levels? Glycogen-depleting exercise and intermittent fasting do; they also lead to an increase in cortisol levels.

Ned Kock said...

Hi Lerner, thanks. The fear-mongering situation that has been developing lately regarding blood glucose reminds me a bit of the cholesterol situation – which still persists.

Some may argue that this is all due to measurement. I’d disagree, and argue that among the main problems are bad measurement and bad interpretation of results.

Ignoring measurement is a self-defeating proposition, as someone will surely come up with measurement-based papers and related conclusions in the future. Some of those conclusions will be way off mark, and lead to more fear-mongering.

Long-lived individuals see a gradual increase in average blood glucose levels over time, not a decrease:

http://bit.ly/qdFzab

Ned Kock said...

Here is a bit more on the issue of cortisol levels raised by gwarm.

Chronically elevated cortisol, as we see in these traders, is clearly unhealthy:

http://bit.ly/g75Bqg

However, cortisol has a number of body functions, probably some of which we don’t know yet. For example, with very low levels of circulating cortisol, memorization and learning might be impaired:

http://bit.ly/9ZgRtf

An acute increase in cortisol levels, lasting several days, does not seem like such an unnatural thing. Our Paleo ancestors probably faced situations that would lead to such a response, but not in a chronic fashion.

A few sleepless nights don’t sound like such an unnatural thing either. Would all of our Paleo ancestors have 8 h per night of deep, restful sleep, every day? I doubt it. If not, selection pressure would ensue, and cortisol might have been a factor.

Interestingly, an acute increase in cortisol levels, as described above, would have an interesting effect – it would clear acne and temporarily “cure” allergic reactions.

Cortisol suppresses the immune system. But it also suppresses inflammatory responses. Perhaps these effects occur together for a reason …

Lerner said...

The thing that I've begun to wonder is this: what part of a high serum level of glucose or lipids is the damaging part?

IOW, is it peak plasma, is it the total AUC, is it the duration spent over some damaging threshold?


Btw, what you say about gradual elevation of glucose reminds me of what is also being talked about again wrt blood pressure and the elderly - specifically cognitive ability and organ perfusion. As you know, once upon a time, 'normal' BP was said to be age + 100, then the goal became to keep it at a low target. But now AFAIK there is a bit of talk again to let it rise.

Ned Kock said...

Here is a bit more on IR and Peter’s points, mentioned by gwarm. And, thanks gwarm for raising these issues.

When Peter (Hyperlipid) talks about the benefits of peripheral IR, which is closely related to what he calls physiological IR, he correctly points out that it prevents death, by preventing hypoglycemia.

Looking at glucose levels and how they can vary shows just how this is a very, very good point that should always in the back of anyone’s mind when they think about glucose levels.

In the absence of peripheral IR, how much would it take to lead to severely low blood glucose levels – say, about half of 100 mg/dl?

Well, a person with a blood glucose level of 100 mg/dl will have about 5 g of sugar in the blood:

http://bit.ly/qSLDkd

So it would take the disappearance of 2.5 g of sugar to lead to severely low blood glucose levels. Not life-threatening yet, but low enough to cause some seriously unpleasant symptoms.

How much body movement would consume 2.5 g of sugar, without some form of IR, in this case clearly physiological IR? I am not sure, but I’d say not much. Our brain alone consumes about 5 g of sugar per hour, whether you are sitting quietly or not …

Lerner said...

"Cortisol suppresses the immune system. But it also suppresses inflammatory responses. Perhaps these effects occur together for a reason …"

I don't believe you can have an inflammatory response which is not mediated by immune cells. Even when twisting your knee, it is the mast cells that excrete the histamine that starts things out. Then you'd eventually end up with macrophages doing the scavenging to clean up.

Also, there are studies of monkees/primates whose stress hormone levels are higher as they themselves are lower on the dominance hierarchy. Also there are studies on British civil servants showing the same effect. So I'd guess it was not an idyllic existence for the cavemen either, lolling about stress free :) Most stress might have come from fellow humans rather than predators.

And btw, the worst outcome of low cortisol would be an Addisonian Crisis which can = death.

Gretchen said...

Ned:

In answer to your question, pre-Dx, my mother ate what was probably a fairly standard American diet, but she had a big garden and ate vegetables from that and shopped at a Coop with organic food.

After the Dx (which occurred after a cancer operation), she was put on the high-carb, low-fat ADA diet and lost a lot of weight and her doctor said they wondered if she'd ever had diabetes at all.

At that point she reverted to her previous diet and regained all the weight, plus some.

At one point, at my suggestion, she tried a LC diet and said she'd never felt so good, but she didn't really understand what carbs are ("But I thought oatmeal and prunes and orange juic were healthy") and abandoned it.

In her last years, she was eating what many would consider a healthy diet (lots of vegetables, chicken and fish, and some red meat), but her caregivers believed in low fat, so they'd give her "healthy" organic low-fat brownies and things like that.

At that point, I felt that enjoying her food was more important than a low A1c, so I didn't lay down the law. Her doctor and I also agreed that she was taking so much medication for her heart that additional medication for the mild diabetes wasn't a good idea.

Lerner: Look into follow-up studies of the infamous Accord study that has doctors telling their diabetic patients to increase their A1cs. It was only the patients who were unable to lower A1c despite masses of drugs who did worse.

David Isaak said...

Apropos of this and your previous post, a recent study found that fasting blood glucose is not a predictor of CV problems in T2 diabetics.

http://care.diabetesjournals.org/content/34/10/2237

High postprandial levels after lunch, however, were predictive. Breakfast wasn't. They do some handwaving to explain that away:

http://www.theheart.org/article/1278655.do

David Isaak said...

@Lerner--Some studies show that while the lower-ranking elements of the pecking order experience more damaging stress than higher-ranking members, the top dog (or, rather, ape) also experiences a lot of stress.

Apparently the best place to be is near the top but not in charge--the Grand Vizier rather than the Caliph. Conultant rather than CEO.

Ned Kock said...

Hi David. Another alternative is for the CEO not to act like an alpha male monkey would, being more of a motivator than a drill sergeant, and reap the benefits in terms of health.

It seems like Alan Mulally generally follows that approach, in an industry where management-employee relations can be quite contentious.