Spikes in blood glucose levels can lead to clogged arteries
A new study by researchers in the US and Australia could explain why diabetics are at higher risk of heart disease. They have found that the brief spikes in blood glucose levels that occur between doses of glucose-lowering drugs can trigger a biochemical response that clogs up arteries.
The team, led by Assan El-Osta at the Baker International Diabetes Institute in Melbourne, Australia, has shown for the first time that these short-lived sugar highs can trigger changes in gene expression that lead to the formation of atherosclerotic plaques - the build-up of white blood cells on artery walls that causes the narrowing or ’furring’ of arteries and reduces blood flow to the heart.
El-Osta and his colleagues used cultured human cells from the lining of the aorta - the largest artery in the body. They found that when the cells were exposed to short bursts of high glucose, or hyperglycaemia, reactive oxygen species (ROS) were formed.
ROS are by-products of glucose metabolism. When they oxidise proteins and lipids in the cell a carbonyl compound called methylglyoxal builds up, which activates an enzyme that attaches a methyl group to histone proteins. Histones provide a kind of protein spool for DNA to wind around, and help to regulate gene expression. In this case they increase the expression of genes that are involved in inflammation. These genes produce proteins that attract white blood cells to the blood vessel wall, causing artery-clogging plaques.
Smoothing the spikes
Controlling glucose spikes could offer a new route to reducing the risk of heart disease in diabetics. Recently published research has already highlighted the fact that there is more to managing the disease than simply lowering blood glucose.
A high-profile clinical trial published in the New England Journal of Medicine showed that using drugs to intensively lower the blood glucose levels of diabetics in the hope of reducing heart problems was ineffective.2
And earlier this year, in an article in the Journal of the American College of Cardiology, James O’Keefe from the University of Missouri-Kansas City also pointed out that modern diet and lifestyle - especially the ’highly processed, calorie-dense, nutrient-depleted diet favoured in current American culture’ - could exaggerate fluctuations in blood glucose.3
Hertzel Gerstein, professor of diabetes research at McMaster University in Ontario, Canada says that this new study ’could provide clues leading to new cardioprotective therapies’.
But John Buse, the director of the University of North Carolina’s Diabetes Care Center adds a note of caution. ’This is a beautifully done set of studies in a highly artificial system that may or may not have direct relevance to human disease,’ he says.
et alJournal of Experimental MedicineNew England Journal of Medicine358et alJ Am Coll Cardiol51, 249 (DOI:10.1016/j.jacc.2007.10.016)