(Philadelphia, PA) - Intensive glucose control lowers the risk of heart disease and stroke by about 50 percent in people with type 1 diabetes, researchers report in the December 22, 2005, issue of the New England Journal of Medicine. Their findings are based on a follow-up study of patients who took part more than a decade ago in the Diabetes Control and Complications Trial (DCCT), a major clinical study funded by the National Institutes of Health. The Division of Endocrinology, Diabetes, and Metabolism at the University of Pennsylvania School of Medicine, with physicians from the Children’s Hospital of Philadelphia (CHOP), was one of 28 centers across the country that participated in the DCCT.

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. At the time, however, researchers had not followed participants long enough to know whether tight control also lowered the risk of heart attack and stroke.

“Now we know that intensive glucose control with insulin also protects the heart and blood vessels,” says Stanley Schwartz, MD, Associate Professor of Medicine, who along with Lester Baker, MD, (now deceased), from CHOP, led Penn’s participation in the DCCT and the follow-up study of DCCT participants. “Maintaining tight control is challenging, but easier than ever with the newer insulins available and it confers huge benefits, both in the short and long term. Intensive control should begin as soon as possible and be maintained as long as possible.”

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) levels 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.)

The DCCT findings--that intensive glucose control greatly lowers the eye, nerve, and kidney damage of type 1 diabetes--prompted a major shift in the way doctors manage their patients with type 1 diabetes. At the end of the study, HbA1c levels 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.

As researchers continued to follow participants over the next decade, they observed another advantage of intensive control: its long-lasting effects. The benefits of the first 6 years of intensive control persisted even though the average blood glucose level of the intensively treated group had gradually risen to a HbA1c value of about 8 percent-the same level of the conventionally treated group, which had declined.

In the most recent results, tight glucose control lowered the risk of a CVD 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 CVD 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 CVD 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 NIH-funded study are due in 2009.

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 about 5 to 10 percent of all diagnosed cases of diabetes in the U.S. This form of diabetes usually strikes children and young adults, who need three or more insulin injections a day or 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.

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