Understanding the diabetic heart

| Written by Deborah Robison
Dan Kelly with Ling Lai and Teresa Leone

Daniel Kelly, M.D., cardiologist and director of the Center for Metabolic Origins of Disease at Sanford Burnham Prebys Medical Discovery Institute in Lake Nona, was interviewed about the effects of diabetes on the cardiovascular system. Here’s a shortened version of that conversation.

How do diabetes and cardiovascular disease intersect?

We see a more aggressive form of heart and vascular disease in diabetics. In addition, diabetic forms of cardiovascular disease appear to have different root causes compared to what we would call run-of-the-mill heart disease in the non-diabetic population. Given the increasing prevalence of type 2 diabetes, this form of heart and vascular disease has led to a worldwide health crisis. Moreover, the standard therapies currently used after a heart attack or to prevent a heart attack don’t work nearly as well in diabetics.

How will therapies change in the future?

Therapies aimed at reducing blood pressure, such as diuretics, reduce demands on the failing heart and have been somewhat effective in reducing mortality from heart failure. However, metabolic changes that are distinct from what happens with high blood pressure or a heart attack also contribute to heart failure. Diabetes is a metabolic disease that has profound effects on lipid and fat metabolism. We’re trying to understand whether these metabolic derangements actually promote heart failure in diabetics. This should lead to therapies aimed at the metabolic origins of cardiovascular disease.

How is lipid metabolism related to diabetic heart disease?

Because of what happens to blood sugar in diabetes many physicians have been, if you will, “glucose-centric”. What we’re beginning to find is that the diabetic heart begins to accumulate fat. The heart, liver and other organs can't use sugar because there is not as much insulin as there should be, and its effects are reduced. Therefore, the organs shift over to use fat as the main fuel. The problem is that this becomes maladaptive and these organs take up too much fat and develop what we refer to as "lipotoxicity." Reducing the accumulation of fat in the heart ameliorates heart failure in animal models. This is a very exciting finding and raises the question of whether our current therapies for heart failure, which are not directed at all at the lipid problem, will be effective in the diabetic population.

What will future therapies look like for lipotoxicity?

I can envision therapies that work on organs other than the heart, such as at fat tissue, muscle or the liver, that would actually burn up fat. In this regard weight reduction in the obese should be effective. Another approach might be to develop therapies that shut down the import of excess fat into cells, effectively “closing the door” on fat . There is real interest in developing agents that would increase the ability of the heart to use glucose again, which, almost like a teeter­totter, would then reduce the amount of fat going in and would provide a healthy balance of several fuels for the heart.

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