kyrasdad
Sat, Jun-07-08, 09:16
Tight Rein on Blood Sugar Has No Heart Benefits (http://www.nytimes.com/2008/06/07/health/research/07diabetes.html?ref=health)
By GINA KOLATA
Two large studies involving more than 21,000 people found that people with Type 2 diabetes had no reduction in their risk of heart attacks and strokes and no reduction in their death rate if they rigorously controlled their blood sugar levels.
The results provide more details and bolster findings reported in February, when one of the studies, by the National Institutes of Health, ended prematurely. At that time, researchers surprised diabetes experts with the announcement that study participants who were rigorously controlling their blood sugar actually had a higher death rate than those whose blood sugar control was less stringent.
Now the federal researchers are publishing detailed data from that study for the first time. Researchers in the second study, from Australia and involving participants from 20 countries, are also publishing their results on blood sugar and cardiovascular disease. That study did not find an increase in deaths, but neither did it find any protection from cardiovascular disease with rigorous blood sugar control.
Thus both studies failed to confirm a dearly held hypothesis that people with Type 2 diabetes could be protected from cardiovascular disease if they strictly controlled their blood sugar.
It was a hypothesis that seemed almost obvious. Cardiovascular disease accounts for 65 percent of deaths among people with Type 2 diabetes. And since diabetes is characterized by high levels of blood sugar, the hope was that if people with diabetes could just get their blood sugar as close to normal as possible, their cardiovascular disease rate would be nearly normal as well.
The two studies were presented Friday in San Francisco at the annual meeting of the American Diabetes Association and will be published next week in The New England Journal of Medicine. The Journal lifted its embargoes to coincide with the presentations at the meeting. A third study, similar but smaller, by the Department of Veterans Affairs, will be presented at the meeting on Sunday.
Diabetes researchers say that the message is that patients should obtain at least moderate control of blood sugar to protect against eye, kidney and nerve disease. But for heart disease, they say, the only proven method of preventing complications is to give statins to control cholesterol, drugs to control blood pressure and aspirin to control blood clotting, and encourage people to lose weight and exercise.
The Australian study did find one advantage to strict blood sugar control — a slight reduction in new or worsening kidney disease. The rate among those with intense sugar control was 4.1 percent as compared with 5.2 percent among those with less intense control.
But researchers disagreed about whether the kidney disease effect in the Australian study was enough to advise patients to strive for rigorous blood sugar control. The Australian investigators said it was.
Others were not so sure. The kidney effect was “a modest benefit,” said Dr. David Nathan, director of the diabetes center at Massachusetts General Hospital. Dr. W. Douglas Weaver, president of the American College of Cardiology, agreed, saying, “It’s hard to get really excited about that data.”
And the excess deaths among patients in the intensive treatment group in the American study gave Dr. Nathan and others pause.
Researchers said it was difficult to compare the studies from the United States and Australia. For example, patients in the two studies took different drugs to lower blood sugar and lowered their blood glucose at different rates — quickly in the federal study, over a period of years in the Australian one.
Those in the federal study used a wide variety of drugs. But all those in the Australian study who were assigned to rigorous blood sugar control were required to take the diabetes drug sulfonylurea gliclazide (modified release), which is not used in the United States.
The study got its major support from Servier, the drug’s maker. Servier had no influence on the conduct of the study or the analysis or publication of its results, said Dr. Stephen MacMahon, a principal investigator and professor of cardiovascular medicine and epidemiology at the University of Sydney.
In both studies, intensive control of blood sugar meant levels of a blood protein, hemoglobin A1C, of 6 percent to 6.5 percent, and less rigorous control meant an A1C goal of around 7 percent to 7.9 percent, typical levels achieved by people with Type 2 diabetes in the United States. The intense control was difficult — participants often ended up taking multiple drugs and injecting themselves with insulin. They also risked severe hypoglycemia from blood sugar levels that plunged dangerously low.
Although the studies’ failure to prove the blood sugar/cardiovascular disease hypothesis was a huge disappointment, the result may reflect how difficult it is to change outcomes in people like the study participants, said Dr. Judith Fradkin, chief of the diabetes division at the National Institute of Diabetes and Digestive and Kidney Diseases. They were middle age or older and had had diabetes for years.
“You’re trying to intervene in people in whom a lot of the damage may already have been done,” Dr. Fradkin said. Younger and newly diagnosed patients may be a different story, she said, adding, “That’s the great unanswered question.”
Still, said Dr. John Buse, president for medicine and science of the diabetes association, the blood sugar/cardiovascular disease hypothesis has failed for people with established Type 2 diabetes.
For these patients, “intensive management of A1C for cardiovascular risk probably isn’t worth it,” Dr. Buse said.
By GINA KOLATA
Two large studies involving more than 21,000 people found that people with Type 2 diabetes had no reduction in their risk of heart attacks and strokes and no reduction in their death rate if they rigorously controlled their blood sugar levels.
The results provide more details and bolster findings reported in February, when one of the studies, by the National Institutes of Health, ended prematurely. At that time, researchers surprised diabetes experts with the announcement that study participants who were rigorously controlling their blood sugar actually had a higher death rate than those whose blood sugar control was less stringent.
Now the federal researchers are publishing detailed data from that study for the first time. Researchers in the second study, from Australia and involving participants from 20 countries, are also publishing their results on blood sugar and cardiovascular disease. That study did not find an increase in deaths, but neither did it find any protection from cardiovascular disease with rigorous blood sugar control.
Thus both studies failed to confirm a dearly held hypothesis that people with Type 2 diabetes could be protected from cardiovascular disease if they strictly controlled their blood sugar.
It was a hypothesis that seemed almost obvious. Cardiovascular disease accounts for 65 percent of deaths among people with Type 2 diabetes. And since diabetes is characterized by high levels of blood sugar, the hope was that if people with diabetes could just get their blood sugar as close to normal as possible, their cardiovascular disease rate would be nearly normal as well.
The two studies were presented Friday in San Francisco at the annual meeting of the American Diabetes Association and will be published next week in The New England Journal of Medicine. The Journal lifted its embargoes to coincide with the presentations at the meeting. A third study, similar but smaller, by the Department of Veterans Affairs, will be presented at the meeting on Sunday.
Diabetes researchers say that the message is that patients should obtain at least moderate control of blood sugar to protect against eye, kidney and nerve disease. But for heart disease, they say, the only proven method of preventing complications is to give statins to control cholesterol, drugs to control blood pressure and aspirin to control blood clotting, and encourage people to lose weight and exercise.
The Australian study did find one advantage to strict blood sugar control — a slight reduction in new or worsening kidney disease. The rate among those with intense sugar control was 4.1 percent as compared with 5.2 percent among those with less intense control.
But researchers disagreed about whether the kidney disease effect in the Australian study was enough to advise patients to strive for rigorous blood sugar control. The Australian investigators said it was.
Others were not so sure. The kidney effect was “a modest benefit,” said Dr. David Nathan, director of the diabetes center at Massachusetts General Hospital. Dr. W. Douglas Weaver, president of the American College of Cardiology, agreed, saying, “It’s hard to get really excited about that data.”
And the excess deaths among patients in the intensive treatment group in the American study gave Dr. Nathan and others pause.
Researchers said it was difficult to compare the studies from the United States and Australia. For example, patients in the two studies took different drugs to lower blood sugar and lowered their blood glucose at different rates — quickly in the federal study, over a period of years in the Australian one.
Those in the federal study used a wide variety of drugs. But all those in the Australian study who were assigned to rigorous blood sugar control were required to take the diabetes drug sulfonylurea gliclazide (modified release), which is not used in the United States.
The study got its major support from Servier, the drug’s maker. Servier had no influence on the conduct of the study or the analysis or publication of its results, said Dr. Stephen MacMahon, a principal investigator and professor of cardiovascular medicine and epidemiology at the University of Sydney.
In both studies, intensive control of blood sugar meant levels of a blood protein, hemoglobin A1C, of 6 percent to 6.5 percent, and less rigorous control meant an A1C goal of around 7 percent to 7.9 percent, typical levels achieved by people with Type 2 diabetes in the United States. The intense control was difficult — participants often ended up taking multiple drugs and injecting themselves with insulin. They also risked severe hypoglycemia from blood sugar levels that plunged dangerously low.
Although the studies’ failure to prove the blood sugar/cardiovascular disease hypothesis was a huge disappointment, the result may reflect how difficult it is to change outcomes in people like the study participants, said Dr. Judith Fradkin, chief of the diabetes division at the National Institute of Diabetes and Digestive and Kidney Diseases. They were middle age or older and had had diabetes for years.
“You’re trying to intervene in people in whom a lot of the damage may already have been done,” Dr. Fradkin said. Younger and newly diagnosed patients may be a different story, she said, adding, “That’s the great unanswered question.”
Still, said Dr. John Buse, president for medicine and science of the diabetes association, the blood sugar/cardiovascular disease hypothesis has failed for people with established Type 2 diabetes.
For these patients, “intensive management of A1C for cardiovascular risk probably isn’t worth it,” Dr. Buse said.