Study suggests link between type 2 diabetes and cardiovascular risk

Researchers have identified a link between type 2 diabetes and cardiovascular health issues — even in people with optimally controlled cardiovascular risk factors.

In a new study, scientists have discovered a link between type 2 diabetes and an increased risk of cardiovascular issues, even for people who optimally control the common risk factors for cardiovascular disease.

The research, which appears in the journal Circulation, suggests that early treatment of people with type 2 diabetes for cardiovascular disease may significantly reduce cardiovascular events and mortality.

Type 2 diabetes and heart health

According to the Centers for Disease Control and Prevention (CDC), 1 in 10 people in the United States have diabetes, and of those, 90–95% have type 2 diabetes.

The cells of a person with type 2 diabetes do not react to insulin in the way they should. A person’s pancreas produces insulin, which enables the sugar carried by the bloodstream to enter the cells of the body.

Because blood sugar is not being removed from a person’s bloodstream, their blood sugar levels can increase to dangerous levels. According to the CDC, this can cause vision loss, kidney disease, and heart disease.

Researchers have shown that having type 2 diabetes increases a person’s risk of developing both non-fatal and fatal forms of cardiovascular disease.

Studies also state that people with type 2 diabetes who optimally control common cardiovascular risk factors can reduce their chances of developing cardiovascular events. The authors of the new Circulation study cite research showing that this may prolong a person’s life by up to 8 years.

According to the CDC, risk factors for cardiovascular disease include high blood pressure, high cholesterol, smoking, obesity, an unhealthy diet, low physical activity, and diabetes.

Researchers suggest that people who optimally manage their cardiovascular risk factors could completely negate the associated risk between type 2 diabetes and cardiovascular disease.

In the present article, the researchers wanted to see if this latter study’s findings, conducted with a Swedish population, were reproducible in a population from the United Kingdom.

According to Dr. Alison Wright, first author of the study and research associate at the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester, U.K., “[p]revious studies have shown that people with type 2 diabetes had little or no excess risk of cardiovascular disease events or death when all risk factors are optimally controlled.”

“Our team sought to determine how the degree of risk factor control in people with type 2 diabetes impacted cardiovascular disease risk and mortality, compared to people with type 2 diabetes who had all risk factors optimally controlled and to people who do not have type 2 diabetes.”

Large observational study

To go about this, the researchers looked at clinical data gathered during 2006–2015. The data included over 101,000 people with type 2 diabetes. The team matched these with another group of almost 331,000 people with type 2 diabetes, as well as a group of nearly 379,000 without type 2 diabetes.

Following U.K. clinical guidelines, the researchers looked at five cardiovascular risk factors: cholesterol, triglycerides, smoking, blood glucose, and blood pressure.

They looked particularly at the association between optimally controlling these risk factors and cardiovascular events or mortality in people with type 2 diabetes, compared with people who did not have the condition.

Increased risk

The researchers found that even when optimally controlling the five risk factors for cardiovascular issues, people with type 2 diabetes still had a 21% increased risk of developing cardiovascular disease compared with those without type 2 diabetes.

They also had a 31% increased risk of hospitalization due to heart failure.

For Dr. Wright, the findings suggest that early intervention in cardiovascular risk for people with type 2 diabetes is important:

“People with type 2 diabetes should be treated for cardiovascular risk factors as early as possible, regardless of whether they have cardiovascular disease or not.

“There is real potential here to reduce the overall impact of type 2 diabetes on future cardiovascular events, especially for patients with type 2 diabetes who have not yet been diagnosed with cardiovascular disease.”

The researchers also discovered that people with type 2 diabetes tended to have poor management of cardiovascular risk factors, which scientists note is an international issue, following recent research.

In the present study, only 6% of the participants with type 2 diabetes were optimally managing their risk factors.

As a consequence, Dr. Wright and her co-authors also suggest that “[g]reater use of guideline-driven care, clinical decision support, drug intervention, and self-management support should be encouraged.”

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Can a ketogenic diet prevent heart failure?

A high fat, low carb diet reversed heart failure in a mouse model of the condition. A 24-hour fast also led to improvements, mimicking the physiological effects of the diet.

In people with heart failure, the muscle on the right or left side of the heart — or on both sides — weakens. This impairment limits the organ’s ability to pump blood around the body, causing fatigue and shortness of breath, among other symptoms.

The leading causes are high blood pressure, diabetes, and ischemic heart disease, in which the heart muscle becomes starved of oxygen.

The National Heart, Lung, and Blood Institute estimate that about 5.7 million people in the United States have heart failure.

There is currently no cure, but medications and lifestyle changes can improve people’s quality of life and increase their lifespan.

Healthy heart muscle can draw upon a variety of chemical energy sources, depending on the circumstances. One of these is a molecule called pyruvate, which the body generates during the breakdown of the sugar glucose.

However, conditions such as heart failure and diabetes reduce this flexibility, starving the muscle of the fuel it needs to function effectively.

Fuel shuttle

Researchers have now traced this loss of flexibility to a transporter protein that shuttles pyruvate into mitochondria — the so-called power stations of cells.

Known as the mitochondrial pyruvate carrier (MPC) complex, it comprises two subunits: MPC1 and MPC2.

Researchers at the Saint Louis University School of Medicine in St. Louis, MO, led a team who discovered that the production of both subunits is reduced in failing human hearts.

The researchers compared heart tissue samples from people undergoing heart surgery with tissue samples from donor hearts that were healthy but unsuitable for transplant.

They then showed that mice that lack the gene for producing MPC2 steadily develop heart failure over time. Their hearts became outsized, or hypertrophied, and the organs’ ability to pump blood diminished.

Crucially, the scientists found that they could reverse the damage to the animals’ heart muscle by simply feeding them a special diet for 3 weeks.

“Interestingly, this heart failure can be prevented or even reversed by providing a high fat, low carbohydrate ‘ketogenic’ diet,” explains Kyle S. McCommis, Ph.D., assistant professor of biochemistry and molecular biology at the university, who led the research.

“A 24-hour fast in mice, which is also ‘ketogenic,’ also provided significant improvement in heart remodeling,” he adds.

Ketogenic diet

The ketogenic diet has been growing in popularity in recent years, with research suggesting that it has a range of possible health benefits. These include supporting weight loss, improving heart health, and preventing seizures in some types of epilepsy.

By severely restricting the intake of carbohydrates, such as glucose and other sugars and starches, the diet forces the body to break down fat, producing molecules called ketones that it can use as fuel. Intermittent fasting may achieve similar effects, though adhering to the regimen can be challenging.

The new research indicates that a ketogenic diet promotes the breakdown of fatty acids in heart muscle cells. This process produces an alternative fuel called acetyl-CoA, which the mitochondria can use as an energy source instead of pyruvate.

“Thus, these studies suggest that consumption of higher fat and lower carbohydrate diets may be a nutritional therapeutic intervention to treat heart failure,” says McCommis.

The scientists showed that the diet reversed heart failure by promoting the breakdown of fatty acids in mitochondria rather than ketones. Supplying the mitochondria with extra ketones only slightly improved heart failure.

Converging evidence

The findings from this study appear in the journal Nature Metabolism.

Two studies by other research groups, which feature in the same issue, independently show that the MPC transporter protein plays a central role in heart failure.

P. Christian Schulze and Jasmine M. F. Wu, who are both cardiologists from the University Hospital Jena in Germany, have written a comment article for the journal about the three papers.

While several questions remain unanswered about the regulation of MPC levels in healthy and failing hearts, they conclude:

“The current findings suggest a role for specific ketogenic diets as a supportive, nonpharmacologic treatment in people with heart failure.”

The cardiologists speculate that the findings could also inspire the development of new drugs for heart failure that work by boosting the breakdown of fatty acids in heart muscle cells.

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