The sugar hypothesis of heart disease triumphs yet again over the lipid hypothesis. A study presented recently in Rome and published in the New England Journal of Medicine demonstrates that efforts to lower blood sugar pay off better in lower rates of heart disease and longer life than do efforts to lower cholesterol.  In fact, to be ruthlessly honest about it, efforts to lower blood sugar do seem pay off whereas efforts to lower cholesterol don’t much at all.

Researchers presented data from a long-term study (almost 30 years long) showing that subjects who lowered their blood sugar levels with drugs for a period of 10 years reaped large rewards in terms of reduced incidence of heart attack and reduced incidence of all-cause mortality long after the end of the study.

Here is how the study was done:

From 1977 through 1991 patients were enrolled in a study to determine the benefits (or lack thereof) of intensive glucose lowering with medications (insulin or sulfonylurea) compared to conventional glucose control achieved through diet (more about which later).  Researchers randomized the subjects into the drug-treated, intensive-glucose-control arm or the diet arm of the study and waited and watched for ten years.  At the end of the ten years, the subjects on the intensive-glucose-control arm demonstrated a reduced risk of microvascular complications, a nonsignificant reduction in incidence of heart attack and no improvement in all-cause mortality.  (There was a subset of obese patients in this study who were treated with metformin who showed significant reductions in incidence of heart attack and all-cause mortality by the end of ten years.)

Other than the improvement shown in the obese diabetic patients on metformin and the decrease in microvascular complications, there was no real advantage to the strict glucose control within the ten year study period.  After the study was completed, the subjects were no longer followed regularly for their disease and were returned to the care (or lack thereof) of their own physicians.

Researchers then performed a 10-year post study monitoring just to see what had happen, and were surprised to learn that those patients who had undergone the strict glucose control experienced fewer heart attacks, fewer diabetic symptoms, and lower all-cause mortality.  The reductions in risk were, in my opinion, extraordinary.   There was a 15 percent reduction in heart attacks and a 13 percent reduction in the most important statistic of all: all-cause mortality.

Said one of the directors of the study in a comment that beggars belief and is worthy of the Reckless Award for a stupid statin statement as reported on HeartWire:

UKPDS [United Kingdom Prospective Diabetes Study] has definitively shown today that early glucose-lowering in the longer term really does impact on cardiovascular disease in people with type 2 diabetes. We’re talking about a 13% reduction in all-cause mortality and a 15% reduction in MI. Now, that may not be as big as what we see with a statin or something, but given the millions of people with diabetes, this is a very substantial change, and it is over and above the other treatments that patients are getting.

“Now, that may not be as big as what we see with a statin…”  Are you kidding me?  This guy must be another one who has drunk way too much of the statin-laced cool aid.  If the companies that make statins could get even half… half, hell, if they could get even a third or a fourth of these results, there would be dancing in the streets in statin land.

I’m putting the following in bold so that it will stand out.

As I’ve written countless times in this blog, randomized, placebo-controlled studies (the only kind that matter) have shown that statins provide no decrease in all-cause mortality (the only statistic that really counts) in women of any age whether they’ve ever had a heart attack or not.  These same studies have shown that statins provide no decrease in all cause-mortality in men over the age of 65 regardless of whether or not they have ever had a heart attack.  The only group of people for whom statins have shown any benefit in terms of a decrease in all-cause mortality is men under the age of 65 who have already had a heart attack.  And even in these men, the decrease in all-cause mortality is minuscule.  So minuscule in fact, that some authorities don’t even think the expense of statins is worth the tiny risk reduction.

A 13 percent reduction in all-cause mortality is pretty huge, and seems to be a ‘legacy effect’ of the strict blood sugar control these subjects experienced during the ten years they were on the study.  To be completely accurate, it could be said that the drugs these subjects took are what is bringing about their decreased risk of death, but given the side effects of these drugs, I kind of think that is doubtful.

Chronically elevated blood sugar, even when elevated just a little, is toxic to the blood vessels.  Knowing this, it makes sense that if blood sugar is kept tightly regulated for ten years, less damage should accrue to the vascular systems over this period.  And, since heart disease is the major killer of people worldwide, and since heart disease is a manifestation of vascular damage, it also makes sense that if you minimize vascular damage for ten years, you will have less risk of heart disease and earlier death.  At least that’s the way I see it.

From the hindsight of today, it’s really easy to see why those with tightly controlled blood sugars would have fared better than those on the conventional diet, when you realize what the conventional diet was at the time of this study.  From the original paper in The Lancet (1998) 352(9131) 837-853:

The patients were advised to follow diets that were low saturated fat, moderately high fibre and had about 50% of calories from carbohydrates…

That pretty much tells us all we need to know.  Ten years of a high-carb diet verses ten years of tightly-controlled blood sugar.  Which do you think caused the most vascular damage?

Almost three years ago I wrote another post on the subject of the sugar hypothesis, but that was at a time that this blog had about 12 readers.  Those of you who weren’t readers way back then might want to give this one a look now.  It shows that variations even within the normal range of blood sugars are correlated in a dose-response fashion with mortality.

The take home lesson of these studies is that blood sugar is much more closely correlated to health and longevity than are cholesterol levels.  Yet everyone is focused on cholesterol.  Why?  Because the drug companies want us to be focused on cholesterol.  The pharmaceutical industry has brainwashed the public and, even worse, has brainwashed most of the doctors out there (as evidence, see the quotation above by the director of the UKPDS, who is an academician and should know better).

The nice thing is that it’s pretty easy to tightly control your blood sugar levels without drugs.  How?  By taking blood sugar control out of the hands of your pancreas and turning it over to the liver.  You can do this by keeping your carbohydrate intake low enough to ensure that your liver has to produce glucose.  When the liver gets into the glucose production business, it turns it out in a slow, steady fashion, making just the amount necessary.  Blood sugars stay low, and glucose-induced damage to the vascular system is minimized.  If you follow a good-quality, whole-food, low-carbohydrate diet, your blood sugar will stabilize.  If you’ve already got type II diabetes, following such a diet might not completely solve your problem, but it will make it a lot better.  I have never seen any kind of therapy that works better than a low-carb diet to lower and stabilize blood sugar levels.  It truly is amazing.  If you do have type II diabetes, you must work with your physician to regulate your medications because you will need to reduce your dosages or eliminate the medications very quickly or your blood sugar will fall too low too fast.  As one of my colleagues says when telling other physicians about this therapy: nothing in your medical experience heretofore will have prepared you for how quickly this will work.  And, unlike some other therapies it works everytime

I’m always amazed at how the lipid hypothesis of heart disease has wormed its way deep into souls of physicians, scientists, and medical/nutritional writers the world over. The most flimsy piece of research that seems to confirm this entrenched bias is not only accepted uncritically (not by yours truly, of course), but shouted from the rooftops by the likes of USA Today, the New York Times, Reuters, and other general publications.

Then along comes a study with some true value that, although published in a prestigious journal, is vigorously ignored. Such seems to be the fate of a tremendous piece of research appearing in the current issue of Diabetes Care. Since this journal, like JAMA, makes available to the public the full text of articles its editors deem of significant public health importance, you can get the article in its entirety here.

Researchers at University College in London looked at the mortality data generated over the past 33 years from the Whitehall Study, which, like the Women’s Health Initiative, is a large, government funded study. In the Whitehall Study

18,403 nonindustrial London-based male civil servants aged 40-64 years were examined between September 1967 and January 1970. In brief, measurements included height, weight, blood pressure, six-lead electrocardiogram, lung function (forced expiratory volume in 1 s and forced vital capacity), plasma cholesterol concentration, and a glucose tolerance test. A self-administered questionnaire was completed regarding employment grade, smoking habits, health status, and physical activity.

After an overnight fast the participants of this study underwent a glucose tolerance test in which they drank a preparation containing 50 grams of glucose. Two hours later they had their blood sugars measured. In a normal glucose tolerance test blood sugars typically return to normal within two hours after having consumed a glucose drink. The researchers wanted to record these 2-hr post glucose load figures and see how they correlated with mortality over the ensuing years.

The researchers divided the study participants according to their 2-hr blood glucose values into three groups. Those with 2-hr glucose levels below 95 mg/dl were considered normal; those who measured 96-199 mg/dl were deemed glucose intolerant; and those with 2-hr blood glucose levels at 200 mg/dl or greater were classified as diabetic.

As might be expected, after 33 years the diabetic group fared poorly compared to the normal and even the glucose intolerant group. Having a diabetic 2-hr post load glucose profile increased the odds off all-cause mortality by 2.37 and of death from coronary heart disease by 3.70. Clearly having an abnormal glucose tolerance test is bad news for prospects of a long life, more so, in fact, than a “bad” cholesterol test.

But, the most interesting aspect of this study is what the researchers found in the normal group first at 10 years then at 33 years down the road. Everyone knows that a markedly elevated blood sugar level or a diabetic glucose tolerance test bodes poorly for long term mortality, but what about the lower end of the curve? Is there a difference there? Is there a difference in long term mortality between a blood glucose level of, say, 95 mg/dl and one of 85 mg/dl, both of which are considered normal.

At the 10 year followup of the 18, 403 men the researchers found that heart disease mortality started to increase at blood sugar levels above 95 mg/dl, but that those subjects with blood sugar levels below 95 mg/dl showed no increased risk for death from heart disease.

After 33 years, however, the picture changes. The cutoff level drops to 83 mg/dl. In other words, in terms of cardiovascular mortality, the risk starts to rise as 2-hr post load blood sugars reach 83 mg/dl and that there is a linear increase in risk between 83 mg/dl and 95 mg/dl. I’m sure that after 40 years, the minimum level will drop a few points further.

Why this increase in risk? According to the authors:

Several mechanisms may account for the link between elevated glucose level and CHD risk. A raised glucose level at baseline may indicate emerging insulin resistance and a downward trajectory in glycemic control, with increased risk of glucose intolerance, diabetes, and CHD in subsequent years. Related risk factors, particularly hypertension and an atherogenic lipoprotein profile [even these folks are in the grip of the lipid hypothesis], tend to develop in parallel with insulin resistance. Other pathways include oxidative stress and formation of advanced glycation end products that accelerate atherosclerosis when blood glucose is only slightly raised. A further indirect mechanism involves common antecedents of hyperglycemia and CHD such as poor early growth. Adjusting for conventional risk factors, existing baseline CHD and socioeconomic position in the present study reduced the size of the glucose-CHD association by 45%. This is evidence of a causal role for glycemia in CHD etiology. It is also consistent with an element of confounding and with risk-factor clustering of the metabolic syndrome type.

What needs to be grasped about this study is that there is no comparable study showing mortality related to cholesterol levels, despite all the ignorant hoorah to the contrary. In fact, in this very Whitehall Study researchers measured cholesterol levels and found no significant differences between them in those subjects with normal blood sugar, those who were glucose intolerant, and those with outright diabetes (see Table 1 in the study).

This is all important stuff. It’s much more important for your long term health to work on keeping your blood sugar down than it is to work to keep your cholesterol down. It’s especially important when you realize that most people try to keep their cholesterol levels at bay be consuming a low-fat, high-carbohydrate diet, which is a diet containing, in many cases, a cup and a half to two cups of sugar equivalents per day. Now, remember, a normal blood sugar equates to only a teaspoon of glucose dissolved in the blood. So, it shouldn’t take a rocket scientist to realize that a couple of cups of sugar added to this teaspoon will rapidly run blood sugar levels up, up, up. This misguided effort to focus on cholesterol levels can only end up increasing the risk for early mortality from heart disease, the very thing reducing cholesterol is supposed to prevent.

The maddening thing about all this is that you will probably never read about this tremendously important study in your local paper. But the next time some boob publishes anything that points a finger at cholesterol or, God forbid, fat in the diet, you will read all about it.

Oh, by the way, what’s the best way to keep your blood sugar low? How about by not eating a lot of it and letting the body make the sugar as it needs it. In my clinical experience, most patients on low-carbohydrate diets reduce their blood sugar levels into the 75-85 mg/dl range.