Some people with insulin resistance develop a very severe form of heart disease, for reasons that are not clear. Now, researchers have uncovered two potential biomarkers for severe coronary disease in insulin-resistant subjects.
Insulin resistance raises not only the risk of developing type 2 diabetes, but also of heart disease.
In PLOS ONE, researchers at the University of North Carolina at Chapel Hill School of Medicine describe how they used pigs to show high levels of oxidized LDL cholesterol and glycated proteins (fructosamine or hemoglobin A1c) could be markers for the development of severe coronary disease, especially in females.
First author Timothy Nichols, professor of medicine and pathology, says:
“If these correlations were also found in insulin-resistant humans, then we would want to do everything we could to treat them because they would be at a very high risk of developing severe cardiovascular disease.”
There are tens of millions of Americans with insulin resistance, which raises not only the risk of developing type 2 diabetes, but also of heart disease – where the coronary arteries get clogged up with fatty deposits (a condition called atherosclerosis).
Some people with insulin resistance never develop heart disease, while others experience moderate blockages. However, there are some that go on to develop severe atherosclerosis, with multiple blockages and deterioration of the heart arteries.
Researchers developed an insulin-resistant animal model
To investigate the link between insulin resistance and heart disease, the team developed a first-of-its-kind animal model.
Fast facts about insulin resistance
- Insulin is a hormone that helps cells absorb glucose and use it for energy
- Insulin resistance is where the body produces insulin but does not use it effectively
- Insulin resistance increases the risk of developing type 2 diabetes. If diagnosed early, changes to lifestyle can often prevent or delay progression to diabetes.
Find out more about diabetes
The initial aim was not to pinpoint biomarkers, but to create an insulin-resistant animal that mimicked human heart disease. They chose pigs because they have a similar metabolism to humans, and their hearts are also like ours.
To induce insulin resistance, they put the pigs on a high fat, high salt diet for a year. All the pigs developed coronary and aortic atherosclerosis – but only half developed the most severe form of the disease.
But when they looked for correlations between high insulin resistance and the most severe form of heart disease, the researchers could not find any.
This unexpected result puzzled the team, until senior author David Clemmons, a professor of medicine, and of biochemistry and biophysics, recalled how earlier studies had found a link between atherosclerosis and glycated proteins – proteins bonded with sugars in blood.
And sure enough, when they tested the pigs’ levels of fructosamine and oxidized LDL cholesterol – surrogates for glycated proteins – they found them to be elevated in all the pigs with severe heart disease.
Insulin-resistant females more susceptible
There was also a gender effect in the results. 14 of the 20 pigs that developed severe heart disease were female, and 14 of the 17 pigs that did not develop severe heart disease were male.
Again, this surprised the team, says Prof. Clemmons, who searched the literature for anything similar. He found a study published in 2005 that was done in Finland and showed higher glycated protein levels were strongly associated with advanced heart disease and increased rates of death in women but not in men.
Prof. Clemmons says the underlying mechanisms remain unclear, and adds:
“But now we have a unique animal model that very much mimics what we see in humans. Our model is a good predictor of diet-induced atherosclerosis in females.”
He says they could now look more closely at what is different in the female pigs that increases their susceptibility to severe heart disease when their glycated protein levels are higher.
One step the team is considering is to look in the heart tissue for abnormal biochemistry in the cellular pathways involved in glycated proteins and severe coronary disease.
They conclude that their findings could help researchers further investigate and perhaps target drugs to help people with insulin resistance avoid the worst kind of heart disease.
Funds for the study came from the National Institutes of Health and the North Carolina Biotechnology Center.
Medical News Today recently learned of another study published in Circulation, which suggested PTSD may raise risk of heart attack or stroke in women by up to 60%. The study – the first to look at trauma exposure, PTSD and onset of cardiovascular disease exclusively in women – shows PTSD is not just a mental problem, it can also have a profound effect on physical health.
Written by Catharine Paddock PhD