Understanding the Root of Type 2 Diabetes

Dr. Gerald Shulman is working to uncover what happens in cells that leads to insulin resistance, which is at the core of type 2 diabetes. His research is pointing to new drug targets, as well as exercise and dietary strategies that may lead to the reversal of insulin resistance and the prevention of type 2 diabetes.

In Type 2 diabetes -- the most common type of diabetes -- fat, liver and muscle cells do not respond correctly to insulin. This is known as insulin resistance. As a result, blood sugar cannot enter these cells, where it would be available for energy. Instead, it builds up in the blood.

Medicines to treat type 2 diabetes help manage high blood sugar, but they do little to address its underlying cause. Dr. Shulman and his colleagues are studying the cells of young adults with insulin resistance and a family history of diabetes in order to unravel exactly what happens to cells that cause them to become insulin resistant. The goal: new treatments for type 2 diabetes. The idea is to understand what happens early on in the disease so Dr. Shulman and his team can devise ways of preventing it. They’ve learned that defects in cell components responsible for producing energy may cause more fat to accumulate inside muscle cells. This causes biochemical changes that block insulin from working properly, which may, in turn, lead to insulin resistance.

Dr. Shulman’s research has also shown that even modest weight reductions of 12 to 14 pounds will melt away fat inside liver cells and reverse high blood sugar. Similarly, physical activity affects how cells respond to insulin, reducing insulin resistance.

Diabetes is the fastest-growing disease in the country, but Dr. Shulman is optimistic that it can be beaten. “Now that we are beginning to understand the cellular mechanisms of insulin resistance, which is at the root of type 2 diabetes, we have better therapeutic targets,” he said. “I’m quite excited about it.”