Genetic Disorder May Reveal How Statins Boost Diabetes Risk

Millions of people take statins to lower their cholesterol and reduce the risk of cardiovascular disease. But taking statins does slightly up the risk of Type 2 diabetes. Figuring out whether that means "No statins for you" isn't always easy, despite a proliferation of guidelines intended to help.

Here's in interesting wrinkle: If you've got a hereditary form of high cholesterol you're much less likely to get Type 2 diabetes, according to a study published Tuesday in JAMA, the journal of the American Medical Association.

That's good news for those people, who often have high levels of LDL cholesterol starting in childhood and face a high risk of heart disease and stroke. And it offers intriguing hints as to a possible link between cholesterol receptors in the body and Type 2 diabetes.

To find that out, researchers in the Netherlands delved into an amazing database that has tracked people for familial hypercholesterolemia since 1994. The large number of people tested — 63,320 — made it possible to not only identify people with genetic mutations that caused the high cholesterol, but to show how it runs in families.

The people with familial hypercholesterolemia had a 51 percent lower risk of Type 2 diabetes than their relatives without the disorder. But the diabetes risk for both groups was low: 1.75 percent versus 2.93 percent. It varied based on the particular genetic mutation involved. That difference makes for a nifty demonstration on how genes affect risk, and confirms a link that doctors who treat patients with the disorder have long observed.

And it also may explain why taking statins boosts the risk of Type 2 diabetes in some people.

One theory on how statins work is that they encourage cells to hoover up the bad LDL cholesterol by turning on LDL receptors. That's good for lowering cholesterol levels in the blood, but the study authors said it may also end up damaging the pancreas, which has lots of LDL receptors and controls blood sugar.

"They're speculating that this LDL receptor may be important in some way in determining the risk of diabetes in a statin," says David Preiss, a metabolic physician at the Glasgow Cardiovascular Research Center at the University of Glasgow who wrote an editorial accompanying the JAMA study. "The data they show is quite strongly supportive of that."

"Of course this is very intriguing," says Kees Hovingh, a vascular medicine specialist at the Academic Medical Centre in Amsterdam and a co-author of the study. He and his colleagues are already looking at the cellular level to see how LDL receptors and cholesterol could affect other organs, including the liver and adrenal glands. The research might someday lead to better treatments for diabetes, he says.

The vast majority of people with high cholesterol don't have familial hypercholesterolemia or a genetic mutation that protects them from diabetes. But Hovingh and Preiss both say that doesn't mean people should fear statins. Taking high-dose statins raises the risk of diabetes by 0.3 per every 100 people.

"People who get diabetes in those large clinical trials are the ones who are actually already on the doorstep of diabetes," Hovingh tells Shots. "They're already overweight, obese, have a little bit of hypertension; they're already in the metabolic state." The increased in cholesterol uptake caused by statins might be enough to push them over the edge, he speculates.

"For people who are at borderline risk of getting diabetes, some would say that these are the people who should be cautious about statin therapy," says Preiss, a researcher who also treats patients with high cholesterol. "I don't share that view myself. People at high risk of diabetes are also likely to be at high risk of cardiovascular disease. If I were in that situation I would take statin treatment and just be sure to be screened for diabetes as well."

And figuring out whether statins are right for an individual isn't determined by studies like this; it comes down to the person and a doctor. One persistent woman deployed her daughter's pink calculator to figure it out for herself.