"We see a greater reduction in cardiovascular events from intensive blood glucose control than from drugs that lower blood pressure and cholesterol," said Saul Genuth, M.D, of Case Western University. Genuth chairs the follow-up study of DCCT participants, called the Epidemiology of Diabetes Interventions and Complications (EDIC) study, which is examining the long-term effects of prior intensive versus conventional blood glucose control. "The benefits of intensive control strongly reinforce the message that this therapy should begin as early as possible and be maintained as long as possible."
"The risk of heart disease is about 10 times higher in people with type 1 diabetes than in people without diabetes," added David Nathan, M.D., of Massachusetts General Hospital, who co-chairs the study. "Maintaining tight control is difficult, but its advantages are huge. Intensive glucose control significantly reduces heart disease as well as damage to the eyes, nerves, and kidneys of people with type 1 diabetes. The longer we follow patients, the more we're impressed by the lasting benefits of tight control."
The DCCT results, announced in 1993, clearly showed that intensive glucose control prevents or delays the eye, nerve, and kidney complications of type 1 diabetes. However, researchers had not followed participants long enough to know whether tight control also lowered the risk of heart attack and stroke.
The DCCT compared intensive management of blood glucose to conventional control in 1,441 people with type 1 diabetes. Patients 13 to 39 years of age took part in the trial between 1983 and 1989. At the time, conventional treatment consisted of one or two insulin injections a day with daily urine or blood glucose testing. Participants randomly assigned to intensive treatment were asked to keep glucose levels as close to normal as possible. That meant trying to keep hemoglobin A1c (HbA1c) readings at 6 percent or less with at least three insulin injections a day or an insulin pump, guided by frequent self-monitoring of blood glucose. (HbA1c reflects average blood glucose over the past 2 to 3 months.)
Researchers announced the DCCT's main results in 1993: intensive glucose control greatly lowers the eye, nerve, and kidney damage of type 1 diabetes. At the end of the study, HbA1c readings averaged 7 percent in the intensively treated group and 9 percent in the conventionally treated patients, who were then encouraged to adopt intensive control and shown how to do it. The DCCT findings prompted a major shift in the way doctors manage their patients with type 1 diabetes.
As researchers continued to follow participants, they saw that intensive treatment reduced the development of atherosclerosis, a finding published in 2003. They also observed a striking advantage of intensive control: its long-lasting effects. The benefits of the first 6 years of intensive control persisted even though the blood glucose level of the intensively treated group had gradually risen to a HbA1c reading of about 8 percent, matching that of the conventionally treated group, which had declined.
In results reported today, tight glucose control lowered the risk of a cardiovascular event by 42 percent and the risk of a serious event, including heart attack or stroke, by 58 percent. Among the 1,375 volunteers continuing to participate in the study, the intensively treated patients had less than half the number of cardiovascular events than the conventionally treated group (46 compared to 98 events). Such events included heart attacks, stroke, angina, and coronary artery disease requiring angioplasty or coronary bypass surgery. Thirty-one intensively treated patients (4 percent) and 52 conventionally treated patients (7 percent) had at least one cardiovascular event during the average 17 years of follow-up from the start of the DCCT. The average age of participants is now 45 years; 53 percent are male.
Is glucose control as important for people with type 2 diabetes? Mounting evidence suggests that tight control benefits everyone with diabetes, but strict control is hard to sustain and can lead to episodes of hypoglycemia, or low blood glucose. Researchers expect that a definitive answer will come from the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes), a major study testing ways to lower the risk of heart disease and stroke in adults with type 2 diabetes. Results of this study, sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and co-funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), are due in 2009.
DCCT and EDIC were funded by the NIDDK, other components of the National Institutes of Health (NIH), and Genentech, Inc., which supported the studies through a Cooperative Research and Development Agreement with the NIDDK.
Nearly 21 million people in the United States--7 percent of the population--have diabetes, the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke. At least 65 percent of people with diabetes will die from a heart attack or stroke, yet two out of every three people with diabetes are unaware of their increased risk.
Type 1 diabetes accounts for 5 to 10 percent of all diagnosed cases of diabetes in the United States. This form of diabetes usually strikes children and young adults, who need three or more insulin injections a day or treatment with an insulin pump to maintain the level of blood glucose control shown to prevent or delay long-term complications. Most people with type 1 diabetes who were treated with conventional glucose control, as it was defined before the DCCT, develop one or more complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys. Today, such complications are much less likely to occur if patients begin intensive treatment promptly after the onset of diabetes.
In its "Be Smart About Your Heart: Control the ABCs of Diabetes" campaign, the National Diabetes Education Program (www.ndep.nih.gov/), jointly sponsored by the NIH, the Centers for Disease Control and Prevention, and 200 partner organizations, encourages people with diabetes to control their blood glucose as well as their blood pressure and cholesterol. By keeping all three as close to normal as possible, people with diabetes can live long, healthy lives. NIDDK information about diabetes is available online at www.niddk.nih.gov.
NIDDK and NHLBI are components of the NIH under the U. S. Department of Health and Human Services. The NIH is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, see www.nih.gov.
Journal
New England Journal of Medicine