Nov 25, 2008 - Research

Combination of Genetics and High Blood Sugar May Mean Extra Heart Disease Risk for Diabetics

Diabetics have to be worried about more than just their cholesterol when it comes to the health of their arteries. They also have to watch their blood sugar to help prevent the build up of fatty plaques that can block blood flow.

But new research from the Joslin Diabetes Center and Harvard Medical School shows that high blood sugar may be more dangerous to some diabetics than others.

Dr. Alessandro Doria and colleagues found that a genetic variant on chromosome 9 previously associated with coronary artery disease (CAD) risk in the general population has an even greater effect in diabetics with poor blood sugar control. These results, published online today in the Journal of the American Medical Association, could someday help doctors identify people with diabetes who are at higher risk of CAD earlier, allowing them to aggressively target these patients for intervention.

People with diabetes are at least twice as likely as those without to have heart disease. Some studies suggest that middle-aged diabetics have the same high heart attack risk as people without diabetes who have already suffered a heart attack.

The first of two study groups was composed of 322 diabetics with coronary artery disease and 412 without. The researchers found that the risk for CAD was about the same in people with either the AA or AG genotype at rs2383206, even if they had poorly controlled blood sugar.

Having the GG genotype at rs2383206, however, increased the odds of CAD by about two-fold for diabetics with well-controlled blood sugar. And when high blood sugar was thrown into the mix, the odds of CAD for people with two Gs went up higher still — about four times compared to the lowest risk group.

In people with the GG genotype and a long history of high blood sugar, the odds of CAD were increased about seven times compared to diabetics with a history of well-controlled blood sugar.

(The study looked at rs2383206, which is available to 23andMe customers who were genotyped on the second version of our custom chip. But people who were genotyped on the first version can use rs2383207, the SNP we feature in the Health and Traits research report on Heart Attack, as a substitute. The G version is riskier for both SNPs.)

In a separate study group of 475 diabetics who were followed for 10 years, people with the AA or AG genotype at rs2383206 had the same risk of dying in general, or from cardiovascular disease in particular, regardless of their blood sugar. But for people with the GG genotype, the risk of death went up by a factor of two when blood sugar was not under control.

Both groups of diabetics Doria et al. studied were of European ancestry.

“While good glucose control is important for all people with diabetes, testing for this predisposing variant may help doctors identify patients for whom better control is an absolute necessity,” said Doria in a statement. The authors estimate that 30% of diabetics will have two Gs at rs2383206.

The probability of clinically significant CAD is about 30% for type 2 diabetics in general. The authors say this number could shoot up to 60% for diabetics with the GG genotype at rs2383206 and poorly controlled blood sugar.

The authors admit that this is a small study that will need verification. They also note that their findings are at odds with a previous report that found no difference between the risk conferred by SNPs in the 9p21 chromosomal region (where rs2383206 lies) in diabetic vs. non-diabetic subjects. Due to a number of methodological differences between the two studies, Doria et al say that no direct comparison of the results is possible.

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