Could HDL Be Bad for You?

Patient Expert

Are high levels of "good cholesterol" always good for you? A new study suggests perhaps not if you have diabetes.

HDL (high-density cholesterol) is supposed to be the "good cholesterol," or the "healthy cholesterol." It removes excess cholesterol from the blood and brings it back to the liver to be recycled.

HDL, together with estrogen, also helps stimulate the production of nitric oxide, which can relax blood vessels and lower blood pressure. HDL also has other beneficial functions as well.

It's the LDL (low-density cholesterol) that is the "bad cholesterol," or "lethal cholesterol." That's the stuff that forms plaques on your arteries that can clog them or, even worse, break off and cause heart attacks and strokes.

But now a study has shown that in "diabetics," not only does HDL fail to protect arteries by stimulating the production of nitric oxide, but it also seems to prevent arterial dilation by nitric oxide when other artery-dilating compounds are given.

The HDL from "diabetics" seems to have this effect because it associates with a 14-carbon saturated fatty acid called myristic acid. The association causes the deleterious effects.

Does this research, performed by Eric J Smart and colleagues at the University of Kentucky and published online the American Journal of Physiology Cell Physiology, mean that people with diabetes should be concerned about having high HDL levels?

The answer is that no one knows for sure yet. One problem is that the "diabetic" patients used in the study were not sufficiently described. The paper did not indicate if they were type 1 or type 2, nor how well controlled they were, as there was no mention of A1cs. It did not say how many patients were tested, nor whether the researchers tested a lot of individual samples and got the same results with all of them, or if they pooled the blood samples and tested the pooled blood.

The patients' fasting levels were 211 plus or minus 28 mg/dL, which suggests that these patients would have had high A1cs. Fasting triglyceride levels were 521 plus or minus 92 mg/dL, which is very high. Triglyceride goals are less than 150. Fasting insulin levels were three times "normal" serum levels, which suggests type 2.

The researchers used a OneTouch Ultra meter to measure blood glucose (BG) levels in the mice who were tested along with the humans. They don't say how they measured BG levels in the humans.

Hence it's difficult to know what this study really means for human diabetes patients. The researchers did a lot of controls, and the effects seem to be consistent: in both the diabetic mice and diabetic human blood samples, the HDL did not have the same beneficial effects as it did in nondiabetic blood samples.

But was this because the diabetic humans and mice had high BG levels? Or was it some metabolic defect that occurs when you have diabetes, regardless of the level of your control?

The researchers found that adding myristic acid to HDL samples from people without diabetes had the same effect as the HDL from people with diabetes. They found this to be true in dose-dependent fashion. In other words, when they added a little myristic acid to nondiabetic HDL, they got a small effect; when they added a lot, they got a large effect.

Do people with diabetes produce or fail to break down more myristic acid than people without diabetes? Or is their HDL modified in some way that makes it complex with myristic acid when the fatty acid is present at low levels? The researchers did not speculate about this in their article, and they did not respond to my e-mail queries.

Despite these limitations, this is an interesting study that should be followed up. It illustrates the fact that there's still so much we don't know about diabetes and lipid levels. In fact, HDL isn't homogeneous. There are different types of HDL. Two are called HDL2 and HDL3. There is some disagreement about the relative beneficial effects of the HDL subtypes, and also about whether wine, which is known to increase HDL, increases a beneficial form of HDL or not.

Another apparent contradiction is that Smart's team has found that HDL and estrogen act together to produce nitric oxide, which acts as an anti-inflammatory agent and protects against heart disease. This is cited as one reason premenopausal women have lower rates of heart disease than men. HDL from premenopausal women and postmenopausal women receiving hormone replacement (estradiol) had more effect on nitric acid production than HDL from men.

But another study showed that oral estrogen is proinflammatory and increases cardiovascular risk, explaining why hormone replacement therapy seems to increase heart attack risks, at least in older women.

Interestingly, transdermal estrogen did not have the inflammatory effects of oral estrogen, which illustrates the fact that you can't always mimic natural physiological effects with pills or shots. The effects may depend on the route.

This is true of insulin, which doesn't have the same effects when injected as it does when produced naturally in the pancreas, where it first goes through the liver. As a result, liver insulin levels are much higher than levels in the periphery. When injected, the levels are higher in the periphery and lower in the liver.

An editorial in Arterosclerosis, Thrombosis and Vascular Biology describing the seemingly proatherogenic properties of estrogen and HDL points out some other important caveats when assessing research studies: "Just because a biomarker is associated with coronary heart disease (CHD) events in epidemiologic studies is not a guarantee that pharmacologically altering the biomarker will result in changes in CHD risk in the anticipated direction."

This seems to be true with homocysteine, which has been associated with cardiovascular disease. But studies in which homocysteine levels were lowered with drugs found no change in cardiovascular events.

All these caveats should all be kept in mind when thinking about the research showing that HDL from "diabetics" seems to increase cardiovascular risk. I'd be willing to bet the farm (and yes, I actually do own a farm), that no one really understands all of this yet. Today's research shows one thing; tomorrow's shows something else.

What it does mean is that having high HDL levels doesn't guarantee that you're protected from having heart attacks. "In fact, it appears that for a person with diabetes, having high levels of HDL could be counter-productive," said Smart in a story in the Lexington (Ky) Herald-Leader. "It was an outcome that we completely didn't expect. But I think it's really profound, because it says that HDL doesn't always have to be good for you."

So what should you do if you have diabetes and have an HDL level of 70 or 90? I'd say don't panic. If that's your natural HDL level, or if you've gotten your HDL up with exercise, which has other benefits to your health, my intuition says it's a good thing (of course, ask your doctor about it). Artificially increasing your HDL levels with drugs, on the other hand, might not be a good idea until we learn what all this really means, whether it's being "diabetic" that is the problem or whether it's having fasting BG levels of more than 200 that is contributing to the problem.

Even Smart said in the press release that "individuals should not try to lower their HDL levels based on one piece of research."

But this research does suggest that even if you have high HDL levels, you shouldn't figure you're protected and start eating fast food and relaxing on the recliner all day. You should continue to try to eat a good diet (whatever works for you), try to achieve normal BG levels and normal blood pressure, get as much exercise as you are able, and remember to take some time to enjoy life. Laughing helps to reduce stress.

Having diabetes means paying a lot of attention to your health. But you should always keep in mind that you're worth it.