MGmin-low-density lipoprotein (LDL), a form of ultra-bad cholesterol that significantly increases the risk of heart disease, has been discovered by researchers at the University of Warwick, England. The scientists, who wrote about their discovery in the journal Diabetes, say their findings may lead to new therapies for elderly patients as well as those with diabetes type 2.

The British Heart Foundation study found that MGmin-LDL is much stickier than normal LDL and is more common among elderly individuals as well as those with diabetes type 2. It attaches to the walls of arteries more readily, where it forms the dangerous fatty plaques that cause CHD (coronary heart disease).

A significant proportion of patients who have a heart attack also have existing coronary heart disease.

The scientists made human MFmin-LDL in the lab and studied its characteristics and how it interacted with other key molecules in the human body.

If you add sugar groups to normal LDL, it becomes denser and smaller. The process of adding the sugar groups is called glycation. The LDL changes shape, and new regions on its surface are more likely to attach to artery walls, resulting in more accumulation of fatty plaques. As the plaques grow the arteries becomes narrower, resulting in reduced blood flow. The artery can eventually rupture and blood clots can form, raising the risk of heart attack or stroke.

The authors believe that this is why metformin, a diabetes drug which lowers blood sugar levels, reduces the risk of heart disease. Metformin may reduce coronary heart disease risk because it blocks the transformation of normal LDL to the stickier MGmin-LDL.

Dr Naila Rabbani said:

“We’re excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue – of the 2.6 million diabetics in the UK, around 90 per cent have type 2. It’s also particularly common in lower income groups and South Asian communities.

The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralise its harmful effects on patients’ arteries.”

Dr Shannon Amoils, Research Advisor at the British Heart Foundation, said:

“We’ve known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction. This study shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes.

Understanding exactly how ‘ultrabad’ LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients.”

“Glycation of LDL by Methylglyoxal Increases Arterial Atherogenicity – A Possible Contributor to Increased Risk of Cardiovascular Disease in Diabetes”
Naila Rabbani, Lisa Godfrey, Mingzhan Xue, Fozia Shaheen, Michèle Geoffrion, Ross Milne and Paul J. Thornalley
Diabetes May 26, 2011. DOI 10.2337/db11-0085

Written by Christian Nordqvist