Tag Archives: Atherosclerosis

New Advances In Lipid Genetics Lead To Better Detection And Prevention Of Diabetes, Heart Disease

By identifying those at risk at the earliest stage would mean giving individuals plenty of time to make the lifestyle changes that could help them avoid the disease

RESEARCHERS from the US and The Netherlands have found ways to earlier and better prediction of diseases such as diabetes, atherosclerosis, and heart disease through studying the genetic make-up of different varieties of lipids in blood plasma.

Studying the genetic make-up of different varieties of lipids (fatty molecules) in the blood plasma of an individual can lead to a better and earlier prediction of diseases such as diabetes, atherosclerosis, and heart disease, two researchers reported on Monday at the annual conference of the European Society of Human Genetics, currently in session in Amsterdam, The Netherlands.

In the first study, Dr. Joanne Curran from the Texas Biomedical Research Institute, San Antonio, USA, reported that lipidomic profiling would become a more reliable early indicator of individuals likely to develop diabetes than the more commonly used predictors such as blood glucose and insulin levels.

Dr. Curran and colleagues from the US and Australia measured 356 different lipid varieties from about 1100 Mexican American members of large extended families who were part of the San Antonio Family Heart Study. The Mexican American population is at high risk of diabetes with about 25% of this population ultimately becoming diabetic. At the start of the research, 861 of the individuals studied did not have diabetes. However, over the 10 year follow-up examined in the study, 110 individuals did develop the disease.

The scientists were able to isolate 128 different varieties of lipids that predicted the progression to diabetes by measuring the lipidomic profiles of each individual at multiple timepoints during the follow-up period. “The single best predictor we found was a novel component called dihydroceramide (dhCer). This was substantially increased in people with diabetes. It is also heritable, and appears to be an independent risk factor unconnected to blood sugar and insulin levels,” said Dr. Curran.

After uncovering the link between dhCer and diabetes, the team searched the genome to find locations that harbored genes that influence dhCer levels. They identified a region on chromosome 3 that appeared to contain a gene with substantial importance for the production of dhCer. “Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment,” Dr. Curran said.

Dr Joanne E. Curran

In the future, the researchers say, measurement of dhCer levels could become routine in the prediction of individuals likely to become diabetic. One of the difficulties of the current predictive methods is that they do not function until a patient is near to developing the disease. Being able to identify those at risk at the earliest stage would mean that individuals have plenty of time to make the lifestyle changes that could help them avoid the disease – through a change in diet, or increasing physical activity, for example.

“Currently one in ten US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050,” said Dr. Curran. “We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated. A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness. It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous”, she was quoted saying in a press release.

In the second study, Dr. Sarah Willems, from the Erasmus Medical Centre, Rotterdam, The Netherlands, described to the conference research carried out on the influence of common genetic lipid variants on atherosclerosis and related heart disease. “A recent genome-wide meta-analysis of more than 100,000 individuals identified a large number of genetic variants associated with levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. These molecules are, at increased levels of LDL and triglycerides and decreased levels of HDL, important risk factors for cardiovascular disease”, said Dr. Willems.

Dr Sarah Willems

“As our knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events,” Willems’ group told attendees.

The researchers used risk scores from these genetic variants to test the hypothesis that their cumulative effects were associated with cardiovascular disease. For this purpose they used genetic data from more than 8000 individuals from the population-based Rotterdam Study and more than 2000 individuals participating in the Dutch family-based Erasmus Rucphen Family study.

They found an association between the LDL risk score and arterial wall thickness, and a strong association of this risk score with carotid plaque. These conditions can cause arterial blockage which leads to stroke. The same risk score was also associated with coronary heart disease.

“Our findings show that an accumulation of common genetic variants with small effects on lipid levels can have a significant effect on clinical and sub-clinical outcomes”, said Dr. Aaron Isaacs, who led the project. “In the future, as our knowledge of genetic variation increases, effective pre-clinical genetic screening tools may be able to enhance the prediction and prevention of diseases such as cardiovascular disease.”

New genetic variants influencing lipid levels are being identified all the time, the researchers say. “As new variants are discovered, we would like to be able to continue to test them, both singly and combined, for association with cardiovascular disease. The cost of these diseases to individuals, families, society and healthcare systems is immense”, said Dr. Willems.

“Cardiovascular disease is the main cause of death in Europe, killing over 4 million people per year. It also represents 23% of the total disease burden (illness and death) across the continent. Managing cholesterol levels is important for prevention. This can be done early in life by effective treatment. We hope that our study, showing that common genetic variants play an important role in the occurrence of cardiovascular disease, marks a starting point for early prediction and prevention and may thus reduce the burden of disease,” she concluded.

Traditional clinical risk factors can predict diabetes and heart disease already, but adding genetic tools to the mix could be useful, particularly in determining how aggressively to approach prevention in patients considered intermediate risk by conventional measures, commented Donna Arnett, PhD, MSPH, of the University of Alabama at Birmingham School of Public Health, and a spokesperson for the American Heart Association.

The cost of genetic testing could be a hurdle for clinical application, though, until ways are found to make it more affordable, she noted in an interview, adding lipodemic profiling is still in its infancy and more information is needed on how measures like dihydroceramide might measure up against clinical factors like waist circumference.

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The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are attending this year’s conference.

Note: These studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Aspirin May Help Diabetics With Kidney Disease Avoid Heart Complications

A new study from a team of Japanese researchers at the Nara Medical University shows that low daily doses of aspirin may help reduce risk of heart disease in patients who have both type 2 diabetes and kidney disease.

Heart disease, as we all know, is the most common cause of death for individuals who have type 2 diabetes because persistently high levels of blood sugar in the veins causes inflammation that leads atherosclerosis, which is a hardening of the arteries that causes the heart to work harder, eventually causing it to wear out.

The research, published in the journal Diabetes Care, concludes that there appears to be a strong relationship between diabetes-induced kidney disease and aspirin therapy. If future studies bear out these results, aspirin could provide a simple solution to a major problem that affects millions of people.

“The current study demonstrated that low-dose aspirin therapy reduced the risk of atherosclerotic events in type 2 diabetic patients,” the researchers wrote in their report.

For the study, researchers gave a group of more than 2,500 participants who had type 2 diabetes and kidney disease either an 81 mg daily dose of aspirin, a 100 mg daily dose or no aspirin at all. The researchers then tracked the participants’ medical records for nearly five years. During this time they checked for instances of stroke, heart disease and peripheral artery disease.

They found that individuals who were in either of the groups that received aspirin had significantly fewer atherosclerosis-related incidences than those who did not receive aspirin.

“The current study demonstrated that low-dose aspirin therapy reduced the risk of atherosclerotic events in type 2 diabetic patients,” the researchers conclude.

Diabetes: Your Arteries May Be Suffering Insulin Resistance

In people with insulin resistance or full-blown diabetes, an inability to keep blood sugar levels under control isn’t the only problem by far. A new report in the May issue of Cell Metabolism shows that our arteries suffer the effects of insulin resistance, too, just for entirely different reasons.

“We think about insulin resistance in liver, muscle, and fat, but insulin also works on vascular cells,” said Christian Rask-Madsen of the Joslin Diabetes Center in Boston. And what insulin does in our arteries sends a signal that helps prevent the buildup of fatty plaques that can cause arteries to harden, new research in mice shows.

Earlier studies showed that in the context of systemic insulin resistance, blood vessels become resistant, too. Doctors also knew that insulin resistance and the high insulin levels to which it leads are independent risk factors for vascular disease. But it wasn’t clear if arteries become diseased because they can’t respond to insulin or because they get exposed to too much of it.

Now comes evidence in favor of the former explanation. Rask-Madsen along with George King and their colleagues find that mice prone to atherosclerosis fare much worse when the linings of their arteries can’t respond to insulin. The animals’ insulin-resistant arteries develop plaques that are twice the size of those on normal arteries.

Insulin-resistant blood vessels don’t open up as well, and levels of a protein known as VCAM-1 go up in them, too.

VCAM-1 belongs to a family of adhesion molecules, Rask-Madsen explained. “It sits on the endothelium and binds white blood cells.” Those cells can enter the artery wall, where they start taking up cholesterol, and an early plaque is born.

“The results provide definitive evidence that loss of insulin signaling in the endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis,” the researchers conclude.

The findings should come as good news to those on insulin therapy, since they suggest the hormone itself should not cause harm to arteries, as some had feared. “If anything, it should be beneficial in preventing atherosclerosis,” Rask-Madsen said.

The results also suggest drugs specifically designed to treat insulin resistance in the vasculature might prevent cardiovascular complications in people with insulin resistance or type 2 diabetes, the researchers say.

While the researchers emphasize that it will remain critical to keep blood sugar in check with more traditional therapies, new treatments aimed at blood vessels could mean big gains for those with diabetes. After all, atherosclerosis is responsible for many of diabetes’ worst complications—heart disease, stroke, and leg amputations among them.

“Atherosclerosis is the main reason for shorter life spans in diabetes patients,” Rask-Madsen said.

Courtesy: machineslikeus.com

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