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Gene For Insulin Resistance Syndrome Linked To Heart Disease

Date:
May 8, 2001
Source:
American Heart Association
Summary:
The discovery that a rare genetic condition speeds the development of heart disease may open the door to new understanding of the link between heart disease and insulin resistance, a problem of blood sugar metabolism, according to a report in Circulation: Journal of the American Heart Association.
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DALLAS, May 8 – The discovery that a rare genetic condition speeds the development of heart disease may open the door to new understanding of the link between heart disease and insulin resistance, a problem of blood sugar metabolism, according to a report in today’s Circulation: Journal of the American Heart Association.

The condition – Dunnigan-type familial partial lipodystrophy (FPLD) – bears striking similarities with a more common metabolic problem called "insulin resistance syndrome" or "metabolic syndrome X." The gene mutation responsible for FPLD causes weight gain in the abdomen, chest and face. Affected individuals also have high insulin levels, high blood pressure, high triglycerides and low levels of high-density lipoprotein (HDL – the "good" cholesterol).

Likewise, syndrome X is characterized by central obesity, high levels of insulin circulating in the blood, high triglycerides, low HDL and high blood pressure. Syndrome X is known to speed the development of heart disease.

Although researchers have suspected the FPLD trait might speed the development of heart disease, this study confirms that suspicion by studying people with the trait.

The study included data on 23 FPLD carriers and 17 controls (family members who did not have the FPLD trait). All the carriers had insulin resistance as well as significantly more type 2 diabetes, hypertension and lipid abnormalities than those in the control group. FPLD carriers had six times the risk of coronary heart disease as their non-carrier relatives in the control group: 34.8 percent vs. 5.9 percent at any age, and 26.1 percent vs. 0 percent before age 55. The average age of developing heart disease was 46.5 years in individuals with FPLD.

"FPLD appears to be an appropriate human single-gene model for insulin resistance syndrome," says author Robert A. Hegele, M.D., a scientist at the Robarts Research Institute and professor of medicine and biochemistry at the University of Western Ontario in London, Ont. "Studying these people might provide some insight for insulin resistance syndrome. Sometimes studying the rare genetic forms of a condition can lead to a better understanding of the common forms."

This approach has worked before. For example, studies of a rare form of high cholesterol led to the creation of the statin class of cholesterol-lowering drugs, now one of the world’s most-prescribed drug groups.

Richard W. Nesto, M.D., a member of the American Heart Association’s diabetes committee says, "We have also learned that patients with asymptomatic diabetes or impaired glucose tolerance have an increased risk of coronary heart disease. The discovery that the insulin resistance syndrome is an expression of a genetic condition can open up new avenues for understanding the mechanisms between insulin resistance and heart disease." Nesto is chairman of cardiovascular medicine at Lahey Clinic Medical Center in Burlington, Mass.

Hegele found the prognosis was unusually bad for women who carried the trait. While six of 23 carriers had heart disease events (angina or heart attack) before age 55, four of those – all women – needed coronary artery bypass graft surgery. The surprising preponderance of women with accelerated heart disease was intriguing, but larger studies are needed to bear this out, he says.

Before menopause, women tend to develop heart disease at a lower rate than men. However, that protection disappears in women who become diabetic.

"This might be an example of that process, but even then you’d expect it to be more of an even balance between women and men. This is an intriguing finding," he says.

Hegele’s lab identified the FPLD gene last year, tracing it to a protein that helps form the matrix or lattice-like material in the nuclear "envelope" that forms a protective shell around a cell’s DNA and other nuclear material. Until recently, the nuclear envelope was considered a mere wrapper rather than the dynamic area that these studies suggest.

FPLD is a dominant genetic condition, which means that it results in insulin resistance in people who carry even one copy of the trait (one copy of the gene comes from each parent). Its prevalence is estimated at between 1 in 100,000 people and 1 in one million people, Hegele says. Since treating his first FPLD patient in 1990, he has treated, studied or located about 60 relatives, all members of a northern European family that immigrated to Canada many generations ago.

Carriers usually develop type 2 diabetes in which blood sugar levels are high despite the high insulin levels. The symptoms in FPLD indicate that high triglycerides and low HDL can be associated with heart disease even when LDL levels are relatively normal.

"Studying individuals with a genetic condition showing this complex interaction may lead to treatments directed at the underlying causes before heart disease becomes evident," says Nesto. "Since patients with diabetes and heart disease have a high death rate if they have a heart attack, any knowledge that leads to more effective primary prevention of heart disease is noteworthy."


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Materials provided by American Heart Association. Note: Content may be edited for style and length.


Cite This Page:

American Heart Association. "Gene For Insulin Resistance Syndrome Linked To Heart Disease." ScienceDaily. ScienceDaily, 8 May 2001. <www.sciencedaily.com/releases/2001/05/010508083521.htm>.
American Heart Association. (2001, May 8). Gene For Insulin Resistance Syndrome Linked To Heart Disease. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2001/05/010508083521.htm
American Heart Association. "Gene For Insulin Resistance Syndrome Linked To Heart Disease." ScienceDaily. www.sciencedaily.com/releases/2001/05/010508083521.htm (accessed March 28, 2024).

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