Type 2 Diabetes Less Common

A new study has found that people with familial hypercholesterolemia have a lower likelihood of having type 2 diabetes compared to their relatives who do not have the disorder.

The study was published today in the Journal of the American Medical Association (JAMA).

Familial hypercholesterolemia is a genetic disorder that causes high levels of low-density lipoprotein (LDL). LDL is known as the “bad” cholesterol.

The disorder causes less LDL to be moved into cells. That is something researchers think lessens cell death. They also believe it leads to lower rates of diabetes in people with familial hypercholesterolemia.

Researchers Studied Patients, Their Families, and the Statin Connection

Dr. John J. P. Kastelein, with the Academic Medical Center in Amsterdam, and his team looked at how common type 2 diabetes was in patients with the disorder and their relatives. They used data from 63,320 people in the Netherlands who underwent DNA testing as part of a national screening program between 1994 and 2014.

pancreas

The researchers concluded that patients with familial hypercholesterolemia had a 51 percent lower risk of having type 2 diabetes compared to their relatives. Researchers noted that the prevalence of type 2 diabetes varied by the type of familial hypercholesterolemia gene mutation. They found an inverse relationship between the severity of the familial hypercholesterolemia mutation and prevalence of type 2 diabetes.

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Statins, the typical treatment for familial hypercholesterolemia, have been associated with increased risk for diabetes. Scientists are not sure why statins are linked to a higher risk for developing diabetes. They believe statins may boost expression of LDL receptors and increase cholesterol uptake into cells. This is, “exactly opposite to the genetically impaired cellular cholesterol uptake in familial hypercholesterolemia” states the study.

“This report adds to the growing literature of a complex interplay between lipids, glycemia, and adiposity, in which statins and other lipid-modifying agents appear to affect diabetes risk,” wrote Drs. David Preiss and Naveed Sattar with the University of Glasgow in the United Kingdom in an editorial on the study.

The Role of Cholesterol Uptake in Type 2 Diabetes

The researchers say their findings coincide with the hypothesis that the common pathway of cellular cholesterol uptake in both familial hypercholesterolemia and statin therapy has a role in type 2 diabetes. That could be because higher intracellular cholesterol levels are harmful for pancreatic beta cell function.

“If these findings are confirmed in longitudinal studies, they might provide support for development of new approaches to the prevention and treatment of type 2 diabetes by improving function and survival of pancreatic beta cells,” the report stated.

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The 51 Percent Difference

Dr. Gerald Bernstein, the director of the diabetes management program at Mount Sinai Beth Israel in New York City, says the difference is significant. But, he asks, what causes it?

“It could be parallel genetic defects not related by physiology,” he said. “Or it could mean that the genetic disorder in some way affects how the insulin-producing cells work, or some other point in the pathway from insulin production to insulin action.”

“It is bound to be a topic for further research,” Bernstein added.

Drs. Preiss and Sattar said the report is one of many that show statins and other lipid-modifying agents appear to affect diabetes risk.

“From a clinical perspective, the findings should allay any concerns about the potential diabetogenic effect of statins when treating patients with familial hypercholesterolemia from childhood or young adulthood given that these patients appear to be at a low risk for diabetes,” they said.

The doctors say the study should not change how statins are used in people with higher cardiovascular risks. For them, statin therapy can still be effective.

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