25 May 2017

Fructose and the diabetic heart

From Our Changing World, 9:06 pm on 25 May 2017

More than a quarter of a million New Zealanders live with diabetes and its many health consequences. These include a high risk of heart disease, which in a person with diabetes is distinctively different from that of a non-diabetic.

Researchers are trying to find out why this is so and what could be done to better treat it.

Kim Mellor

Kim Mellor Photo: RNZ / Alison Ballance

Dr Kim Mellor suspects that fructose may play a role. She leads the Cellular and Molecular Cardiology lab at the University of Auckland and has funding from the Health Research Council to investigate Fructose and the heart: targeting novel mechanisms of diabetic cardiomyopathy.

Cardiomyopathy causes the heart muscle to become enlarged, thick, or rigid. The heart becomes weaker and is less able to pump blood through the body.

“Diabetic patients have a rather unique type of heart complication,” says Kim. “They are quite susceptible to problems with how the heart is contracting and how it relaxes between beats.”

The heart “needs to open up so it can fill with blood before the next beat, and what seems to be quite prevalent in diabetes is that the heart can’t open properly … which means there is not enough blood there to pump out. If that gets really severe it can become diastolic heart failure.”

The role of sugar in diabetic heart disease

Kim says while there are clear correlations between sugar intake, diabetes and cardiovascular disease, there are a lot of gaps in our understanding of what exactly those links are.

Sugar comes in different forms – fructose, glucose and sucrose, which is made up of both a glucose and fructose molecule. Fructose is the sweetest sugar, and is commonly found in fruit, honey and also in high-fructose corn syrup, which is commonly used in the United States as a sweetener.

“What our study is all about is looking at the fructose sugar molecule. So getting right down in to the molecular level we want to know if fructose itself can get inside the heart muscle cells. And can it do something in there, can it change the way that they function and perhaps be underlying some of those problems that are so prevalent in diabetic hearts.”

Not all the fructose in our bodies comes from what we eat. “It may actually be coming from within the cell,” says Kim, and she adds that there is some evidence that diabetic people have higher levels of fructose.

“There is some data out there that shows that circulating or blood levels of fructose increase in diabetic patients, and that’s not well appreciated. Mostly we hear about blood glucose levels.”

She says that we don’t understand exactly what fructose does in the human body and what effect it has on the way the heart functions, and that’s what she is hoping to unravel.

In diabetes, the way that the body transports sugar into the cells is impaired. This is called insulin resistance “because cells are not responding to the insulin hormone to open up the transporters to bring glucose in.”

Kim thinks that what might be happening is that when the cell is not able to use glucose it switches instead to fructose, which is more damaging in the cell.

Some early experimental results are in and Kim is pleased by the findings.

“We’ve shown that if you have some heart muscle cells in culture and you add fructose, the cells will behave quite differently.”

“It’s very clear that the fructose can get into those cells, and it changes the ways those cells contract and relax, which is important to linking it back to a diabetic heart situation.”

Future work

Another important discovery by Kim may prove to be useful in targeting treatment.

“What’s been quite exciting for us is understanding how reactive fructose is from a chemistry point of view,” says Kim. “It is far more reactive than glucose, and can bind to proteins and change the way that they’re structured and the way that they function.”

This process of adding a sugar to a protein which then changes the way it functions is known as glycation.

For the next stage of the research Kim is planning to use gene editing to manipulate the fructose transporters in the cell or the metabolic pathways that handle it.  She says this will help establish whether the fructose is having a direct effect or whether it’s having an indirect effect by influencing something else.

She will be looking at the effect of fructose on rat or mouse hearts, as well as studying cardiac tissue sourced from diabetic patients who have undergone cardiac surgery.

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