March 17, 2008
What’s a Diabetes Patient to Do?
By Kathleen Fackelmann
Donald McEwen was driving on I-480 when he saw an ad on the back of a bus recruiting people for a study on diabetes.
He picked up his cellphone almost immediately.
"I was scared to death," he says now about the pain, fatigue and vision problems caused by his diabetes. "My health was so bad that I thought I would be not long for this world."
McEwen, a salesman from Parma, Ohio, got into the study, took his medication and pushed his blood sugar from dangerously high levels to near normal. The health problems he had suffered for years all but disappeared.
"For me, the program was near-miraculous."
But on Feb. 6, the federal government stopped one part of the study, saying it posed a risk to patients such as McEwen. An independent panel of experts had discovered an elevated risk of death in diabetics who were being aggressively treated to drive blood sugar down to near-normal levels.
The news shocked diabetes experts and patients alike because it challenged the conventional wisdom: Diabetes patients who kept blood sugar close to normal levels were thought to be better off. But that shock quickly turned to confusion a week later when an international team doing a similar study said it could find no such added risk.
The conflicting information has left about 20 million Americans with type 2 diabetes in limbo. No one knows whether the risk of death is real. No one knows whom it might affect. And for now, there's no pat answer about how low to push blood sugar levels.
The truth is, the experts don't have the answers yet, and it could be months before they do. More findings are expected to be released at a major meeting on diabetes in June.
"There's a lot of information we just don't have," says Denise Simons-Morton of the National Heart, Lung, and Blood Institute, the federal agency that sponsored the study that uncovered the death risk. She says U.S. and international researchers have gone back to assess the data and hope to have more information soon.
Clarification is vital, and not just for McEwen and the millions of others who have the disease today. Experts say the number of type 2 diabetics is growing rapidly, fueled by rising obesity among Americans. Researchers at the Centers for Disease Control and Prevention project that by 2050, the number of people who have diabetes will increase 200% from 16 million in 2005 to about 48 million. And of those, 95% will have type 2 diabetes, which is more common in people who are overweight.
The U.S./Canada study
Action to Control Cardiovascular Risk in Diabetes, or ACCORD, was the first large-scale study to try to figure out whether controlling blood sugar levels could reduce the risk of heart disease in people who have diabetes. Cardiovascular disease is the leading cause of death for people with type 2 diabetes.
The ACCORD researchers recruited 10,251 diabetics in the USA and Canada. All were diabetics for at least a decade, and they were at high risk of having a heart attack or stroke.
Patients such as McEwen were assigned to an intensive management program with the goal of driving blood sugars down to less than 6% on the A1C test. The A1C is a measure of how much sugar is in the blood. People without diabetes have an A1C of 4% to 6%. People with diabetes have elevated blood sugar levels, and that is thought to damage blood vessels, the heart and other body systems.
Others were assigned to a usual care group, and they were supposed to get sugars to the standard range of 7% to 7.9%.
Researchers saw patients in the intensive-management group frequently. After four years, the people in that group reduced sugar values to about 6.4%. People assigned to the usual-care group didn't get checked as much, but they still got sugars down to an average of 7.5%
Then the 10-member panel discovered the fatal flaw in the study: They found that 257 people in the intensive-care group had died, compared with 203 people getting the standard treatment.
Previous studies had shown lowering blood sugar could reduce the risk that diabetics would suffer from complications such as vision loss. But John Buse, chief of endocrinology at the University of North Carolina, and others had hoped the ACCORD study would show that near-normal blood sugars could also protect diabetics from heart disease and stroke.
That's why Buse and others were shocked when the study appeared to show the opposite.
"No one expected this," says Buse, who also is the vice chairman of the ACCORD steering committee.
That difference of 54 deaths suggested that for some unknown reason, people in the intensive-treatment group had an increased risk of dying of heart attacks, strokes and other causes. The panel concluded that the potential risk of the intensive strategy outweighed any possible gain, and the federal government halted the study to warn people such as McEwen and Caroyln Gibbons, 65, of Fayetteville, N.C.
Gibbons had taken her diabetes drugs religiously since joining the study. She had lowered her sugars to a 5.3% on the A1C.
"I thought I was doing really well, and then the study's findings came out," she says. Now researchers have told Gibbons to err on the safe side and let sugars rise to 7% to 7.9%.
"I am going up to 7%, but I'm not thrilled about it," she says. She worries that the findings are a fluke and that her health could go downhill. Gibbons says that with an A1C of 5.3% she had fewer problems, such as intense pain in her foot caused by nerve damage.
Different study, different result
Misgivings such as those voiced by Gibbons were heightened when an international team of researchers announced on Feb. 13 that they could not confirm the risk of death. That international study, called ADVANCE, involved 11,140 high-risk diabetics. One group in that study also kept sugars to the normal range by intense treatment.
When the international team went in and examined the number of deaths in their study, they could find no added risk for people who kept sugars close to normal.
Buse says the American researchers now are searching intently for the cause of the high death rate. "It's a little like looking for a needle in a haystack," he says.
The researchers have ruled out some factors that might have been behind the extra deaths. For example, they found no link between the death risk and the drugs used by the participants, including Avandia, which has been linked to heart attacks in people with diabetes.
The ACCORD and ADVANCE researchers will present more complete findings in June at the American Diabetes Association annual meeting. Scientists from a third study, the VA Diabetes Trial, also are expected to weigh in on the question.
"My hope is that the results will sort out then," says Richard Kahn, chief scientific and medical officer for the American Diabetes Association. The ADA plans to assemble a panel of experts to analyze the findings and, if necessary, revise blood sugar guidelines.
Until then, the ADA and other experts urge people with diabetes to stick with the current standards for blood sugar control. The ADA recommends that most diabetics should get sugars down to less than 7% on the A1C.
How low should they go? The jury's still out on that question.
Richard Hellman, president of the American Association of Clinical Endocrinologists, says many younger, relatively healthy diabetics do just fine when they keep their A1C to about 6.5%.
But older diabetics might need to go higher than 7%, Hellman says. Keeping blood sugar close to normal levels can, in some cases, trigger dangerous attacks of low blood sugar, he says.
"You can't write one prescription for everyone," says Faramarz Ismail-Beigi, an investigator in the ACCORD study at University Hospitals Case Medical Center in Cleveland. Until the death risk is explained, patients in the intensive-management group will be counseled to let their sugars rise slightly to the target of 7% to 7.9%.
McEwen says he'll ease up slightly on his medication, but he has no plans to go back to the out-of-control blood sugar levels that led to his health problems.
So while researchers haggle over the scientific questions, McEwen will take the practical approach to his disease. He plans to go out and walk a mile every day. "My weight is 260, and I am 5 feet 8 inches tall," he says, and he knows obesity can make diabetes worse.
He's working with the ACCORD team to cut down on the high-fat comfort foods such as french fries that have contributed to his weight gain. And he says he'll still keep a tight lid on his blood sugar levels.
McEwen had an A1C of 11% when he joined the study in 2005. He has lowered his levels to the normal range, and that effort gave him the miracle he was hoping for the day he picked up his cellphone.
"For a long time I thought I was going blind," he says. "Having my vision back is just wonderful."
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