Reducing cardiovascular risk in diabetics
Is tight glucose control good at reducing cardiovascular risks in diabetics? The data are conflicting, but it is beginning to appear that the answer is yes for some patients but no for others.
In diabetes, every 1% rise in blood sugar level increases by about 20 the risk of heart attack and stroke, which are the disease’s major killers. So doctors and diabetes experts long assumed that lowering a patient’s blood sugar, or glucose, would bring about a parallel reduction in cardiovascular risk.
But the relationship between blood sugar and cardiovascular disease is complex. Now it appears that some patients don’t need to aim as low as others.
Several large clinical trials recently tested the assumption that intense glucose control could lower cardiovascular risks in diabetics . Depending on the trial, patients in the standard groups tried to lower their A1c, a measure of blood sugar over the previous two or three months, to between 7% and 8%, and patients in the intensive groups to between 6% and 7%.
Not only did intensive control appear to do little or no good, but in the case of the subsequently aborted Action to Control Cardiovascular Risk in Diabetes, or ACCORD, trial, such tight control seemed to actually increase the risk of death.
Those findings, along with other disappointing trial results, led some doctors and patients alike to think that tight glucose control might not be good for anybody in terms of lowering cardiovascular risk.
But ongoing analysis is suggesting that the unexpectedly high rate of deaths among ACCORD participants occurred in people who failed to lower their A1c below 7%, not in those who succeeded in lowering it that far.. And three meta-analyses of all the data from ACCORD and the other trials found that, overall, intense glucose control reduced the incidence of heart attack and stroke by about 15%.
So, is tight glucose control good at reducing cardiovascular risks after all? The data are conflicting, but it is beginning to appear that the answer is yes for some patients but no for others.
Lesser effects later
Lowering A1c below 7% does appear to reduce the risk of heart attack and stroke — but not for people who have had diabetes for more than 20 years, who are taking insulin or who already have atherosclerosis, or a hardening of the arteries (a risk factor for heart disease).
A new study by UC Irvine researchers suggests how doctors might determine which patients could benefit from tight glucose control and which might be better off with less ambitious goals.
“If you’re younger, healthier and fairly recently diagnosed with diabetes, it’s very important to aggressively control your blood sugar, because it will reduce your risk of having a heart attack or stroke and from dying from all causes,” said Dr. Sheldon Greenfield, a general internist and a diabetes researcher at UC Irvine who led the study, published in the December 2009 issue of the Annals of Internal Medicine. “But if you’re older and already have cardiovascular disease and other illnesses, and if you’ve had diabetes for a long time, you probably won’t get much benefit in terms of cardiovascular disease,” at least in the short term.
Rather than compare different treatments, his study grouped patients according to how many other illnesses they had. The study followed 2,613 diabetes patients in 204 Italian clinics for five years and tracked the number of non-fatal heart attacks and strokes, and deaths from all causes.
Regardless of blood sugar level, patients who had many other illnesses and long-term diabetes generally had more heart attacks, strokes and deaths.
“In particular, we saw that if you lower glucose levels in people before they get cardiovascular disease or other diseases, they clearly benefit from it. But if you do it after they already have cardiovascular disease, it doesn’t do much good,” said study co-author Dr. Sherrie H. Kaplan, executive co-director for the Center for Health Policy Research at UC Irvine.
Greenfield said that if the controlled trials had stratified patients the way his group did, they might have found similar results.
But participants in the controlled clinical trials mostly had established cardiovascular disease and long-term diabetes. “So we can’t tell from those trials if intensive glucose control would benefit younger, healthier patients with shorter diagnosis and less cardiovascular disease,” said Dr. Theordore Mazzone, chief of endocrinology, diabetes and metabolism at the University of Illinois.
An ongoing multi-center, multi-national trial, called ORIGIN, following patients with pre-diabetes and recently diagnosed diabetes, might begin to answer that question more directly.
It is also possible that the controlled trials did not last long enough for the benefit of glucose control on cardiovascular disease to show up.
“We don’t like to discourage patients, but we tell them it will take a while,” said Dr. Richard Hellman, a diabetes researcher at the University of Missouri-Kansas City School of Medicine. “They will see the benefit of intensive glucose control on nerve damage within three months, on eye disease in two years and kidney disease in three to five years, but they may have to wait more than 10 years to see the benefit in reduced cardiovascular risk.”
Weighing intervention
Dr. Richard Kahn, the recently retired chief scientific and medical officer of the American Diabetes Assn., said excessive glucose is responsible for 15% to 20% of the elevated cardiovascular risk. But he agrees that intense glucose control can be too burdensome for some patients.
The organization has adopted what some call a conservative goal of 7% A1c, but it suggests that doctors can set a more aggressive goal for younger patients or those with no heart disease and a less aggressive goal for older patients with heart disease. “We don’t browbeat older, sicker patients,” Kahn said.
Dr. Yehuda Handelsman, an endocrinologist in solo private practice in Tarzana, also emphasizes the need for individualized treatment. “I tell my patients the lower the A1c the better. But in life, you treat patients with what they have. It’s the art of medicine. I take them step by step and see how far I can bring them down without side effects like hypoglycemia or affecting their quality of life.”
For example, he tells the worried daughter of his 88-year-old, housebound diabetes patient with a slate of other problems and 8% A1c, “Please, let the poor man enjoy his ice cream twice a week.”
