Obesity May Be Only One Piece of Diabetes Puzzle
By GINA KOLATA
The havoc diabetes wreaks is clear. But researchers are puzzled by many aspects of the disease. Why, for example, are most people with Type 2 diabetes overweight or obese, yet most overweight or obese people do not have diabetes?
One clue may lie in the fat cells themselves. The cells release fat and breakdown products of fat — triglycerides and free fatty acids — into the blood. These substances may make cells less able to respond to insulin, increasing the body’s demand for the hormone. Another clue is a paradoxical finding about a hormone, adiponectin, made by fat cells. Adiponectin makes cells more responsive to insulin.
“Oddly enough,” said Dr. C. Ronald Kahn, a diabetes researcher and professor of medicine at Harvard Medical School, “the fatter people become, the less adiponectin their fat cells produce.”
So one way obesity might increase the risk that a person will develop diabetes is by leading to a release of more fatty acids and a decline in adiponectin. This would lead to more insulin resistance and a demand for more insulin. If that demand cannot be met, the result, eventually, would be diabetes.
But figuring out why obesity predisposes some people to diabetes is only part of the puzzle. Researchers also are struggling with a fundamental question. Why does high blood sugar lead to any of the disease’s complications — heart disease, stroke, nerve damage, kidney damage and sight-threatening eye damage?
“On the surface, it seems a little odd,” said Dr. Michael Brownlee, director of the JDRF International Center for Diabetic Complications Research at Albert Einstein College of Medicine in New York. “If your blood has high levels of glucose and it’s bathing every cell in your body, why are only a relatively restricted number of them damaged and the rest just fine?”
It turns out that the unscathed cells are those that can keep out excess glucose. They do this by reducing the number of molecular glucose pumps that every cell uses to transport glucose from the blood to the cell’s interior.
The cells that get damaged lack this ability to tamp down their glucose pumps. They include cells lining arterial blood vessels, small blood vessel cells in the eye and kidney, nerve cells in the legs and feet, and pancreas cells that make insulin — exactly those that are involved in diabetic complications.
But focusing on blood sugar in isolation can give a misleading picture of Type 2 diabetes, said Dr. David Nathan, director of the diabetes center at Massachusetts General Hospital. Going hand in hand with diabetes, for most with the Type 2 form of the disease, are high blood pressure and lipid abnormalities that are linked to heart disease and strokes.
And even though blood sugar levels are the diagnostic hallmark of diabetes, the central fact of diabetes is that patients are not making enough insulin. Insulin, Dr. Kahn said, controls more than just blood sugar. The hormone, he added, also control the body’s use of fats and proteins.
“It is likely that high glucose levels aren’t causing all the complications of diabetes,” Dr. Kahn said. And that is one reason, researchers say, why diabetes care has to include more than just glucose control.
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