Research Profile - Uncovering the Insulin Connection

A researcher at the University of Toronto studies the link between insulin resistance and heart disease.

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Type 2 diabetes doesn't happen overnight. It takes time to develop, and is often preceded by a condition called insulin resistance. Dr. Gary Lewis, Director of Endocrinology and Metabolism at the University of Toronto and Director of the Banting and Best Diabetes Centre, is trying to unravel the sequence of events that leads from insulin resistance to full-blown type 2 diabetes and related illnesses, such as heart disease.

Rates of type 2 diabetes are on the rise around the world, and it is closely linked to heart disease. There is an urgent need for new information on how to treat or prevent diabetes.

"Any impact that a researcher can have on this disease is going to have huge implications for millions of people world-wide," says Dr. Lewis.

Here is what researchers know: in insulin resistance, the important signals that the hormone insulin conveys to all cells in the body, critical for metabolism, are blunted and in some cases nearly absent. In response, the pancreas will boost insulin production, increasing the hormone's levels in the blood. If the pancreas cannot keep up with the demand, both blood sugar levels and the risk of diabetes start to increase.

"Insulin resistance is partly genetically determined, and very much influenced by lifestyle, which influences body weight and physical fitness," says Dr. Lewis.

But no matter the cause, at the cellular level the results of insulin resistance are potentially deadly. Not only do insulin and blood sugar levels veer out of control, but the amount of lipids (the molecules that make up fat) in the blood starts to increase. In addition, the level of "good" cholesterol in the blood decreases. This results in a higher risk for cardiovascular disease.

Dr. Lewis and his colleagues are trying to fill in some of the missing details.

"We ask the questions 'Why?' and 'How?'," says Dr. Lewis. "We feel that if we can understand the mechanisms, then perhaps therapies can be directed to try and correct the mechanisms and reduce the high rates of heart disease."

For instance, researchers have known for some time that the liver boosts lipid production in response to high insulin levels. But Dr. Lewis and his colleague Dr. Khosrow Adeli, at the Hospital for Sick Children in Toronto, discovered that the intestines also increase the production of blood fats in response to high insulin levels.

With support from the Canadian Institutes of Health Research (CIHR), Dr. Lewis is now focused on studying these responses in people who are diabetic or pre-diabetic. His findings could help identify targets for new treatments for diabetes and heart disease.

"My main focus is to really understand the factors that control the overproduction of blood fats by the liver and intestines that accompanies insulin resistance," says Dr. Lewis.