'In fact, it appears that for a person with diabetes, having high levels of HDL could be counter-productive,' says UK biochemist Eric J. Smart, who led the team that made the discovery. '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.'

That seems to fly in the face of more than 20 years of medical wisdom, which has held generally that HDL helps protect us from heart problems.

Reams of medical advice have been written, diets have been devised, and drugs have been developed around the proposition that high levels of 'good' HDL are desirable, and that levels of 'bad' LDL, or low density lipo-protein, should be kept low. Folks whose overall cholesterol tested too high -over 200 -could still take some solace if their HDL number was in the optimal range of 60 or above and their LDL stayed under about 100.

But the UK research, reported recently in the American Journal of Physiology, might suggest that more needs to be learned about HDL.

Smart stressed, however, that individuals should not try to lower their HDL levels based on one piece of research. And he said the best advice for people with diabetes continues to be a healthy diet coupled with moderate exercise. Smart directs the Kentucky Pediatric Research Institute and holds the Barnstable-Brown endowed chair for diabetes research at UK.

Diabetes is a major health problem in Kentucky, and is affecting more and more young people because of they weigh too much and don't exercise.

Smart and his colleagues made their discovery while investigating HDL and diabetes over the past year. They were shocked to find that, in people with diabetes, HDL molecules bind with a natural compound called myristic acid, which somehow causes the HDL to inhibit the body's natural production of nitric oxide, a substance known to protect against cardiovascular disease. Myristic acid is a long-chain fatty acid suspected of increasing cardiovascular risk, Smart said.

The effect was observed in both men and women with diabetes, the researchers said. In effect, HDL in diabetics may reverse its usual role, becoming a potential threat rather than a protectant, the study indicates.

It is still unclear why HDL and myristic acid latch onto each other in people with diabetes, or exactly how that inhibits nitric oxide production.

'What we found was that all of the HDL we looked at, whether it came from people or mice with diabetes, inhibited nitric oxide,' Smart said. 'It was a major surprise to find that it worked the same way in mice and humans.'

Judith Berliner, a professor of medicine and pathology at UCLA, calls the UK study 'an important report.'

'It's a novel finding that this particular fatty acid might be doing this to HDL,' Berliner said. 'The important thing about this paper is that they have identified one change in HDL that seems to be involved in making HDL no longer protective. They don't know what to do about that now, but ... it might allow for some kind of targeting or intervention to make the HDL more protective.'

HDL, along with LDL and triglycerides, are the three lipids that together make up one's overall cholesterol reading. Scientists say that HDL gathers up cholesterol in the blood and carries it to the liver, where it can be excreted from the body. That helps keep cholesterol levels under control, and it's why HDL is considered 'good.' But LDL is thought to deposit cholesterol in arteries, where it can build up to form plaques that impede blood flow and may lead to strokes or heart attacks. It's why LDL has a 'bad' reputation.

Lately, though, HDL's reputation has become a bit mixed.

'There's increasing evidence in the scientific literature that HDL can be either good or bad,' Berliner noted. 'In most people, HDL is protective against atherosclerosis. But in some people, you can isolate their HDL and show that it is not protective.'

Even so, Smart said, when he and his partners began looking at what might happen to lipids in people with diabetes, they never suspected HDL might turn out to be a culprit. 'We thought that diabetes probably would make the LDL worse, or make it do worse things, since it already was known that LDL is bad for you,' he said.

Instead, it turned out that HDL, when it combined with myristic acid, dramatically slowed production of nitric oxide in people with diabetes. To double-check their results, the UK researchers took HDL samples from people who didn't have diabetes.