Tight control of blood glucose level in people with type 1 diabetes reduces the risk of atherosclerosis for at least several years, according to an article in the June 5th issue of the New England Journal of Medicine.

When the Diabetes Control and Complications Trial ended in 1993, researchers learned that strict glucose control greatly reduces diabetes-related damage to the eyes, nerves, and kidneys. With the current analysis, researchers conclude that the benefits of tight control extend to the cardiovascular system.

"Intensive control is difficult to achieve and maintain, but its benefits are even greater than we realized," said study chair Saul Genuth, MD. "The earlier intensive therapy begins and the longer it can be maintained, the better the chances of reducing the debilitating complications of diabetes."

The Trial was a multicenter study that compared intensive versus conventional management of blood glucose in 1,441 people with type 1 diabetes. Patients on intensive treatment kept glucose levels as close to normal as possible with at least 3 insulin injections a day or an insulin pump and frequent self-monitoring of blood glucose. Intensive treatment aimed to keep hemoglobin A1c, which reflects average blood glucose level over 2 to 3 months, as close to normal (6 percent) as possible. Conventional
treatment at the time of the study consisted of 1 or 2 insulin injections a day with daily urine or blood glucose testing.

After 6.5 years of participation in the Trial, hemoglobin A1c levels averaged 7 percent for the intensively treated group and 9 percent for the conventionally treated group. When the Trial ended, people who had been assigned to conventional treatment were encouraged to adopt intensive control and shown how to do it. Researchers began a long-term follow-up study called the Epidemiology of Diabetes Interventions and Complications Study.

The original trial design did not include management effects on atherosclerosis because the participants were relatively young and the trial duration was too short to assess development of atherosclerosis. In 1994-95 and in 1998-2000, Epidemiology researchers used ultrasound to measure the thickness of participants' carotid arteries as a reflection of atherosclerosis in the artery.

At the time of their first ultrasound, the diabetic participants' carotid wall thickness was similar to that of non-diabetic controls matched for age and gender. However, 5 years later the participants had thicker arterial walls than those in the non-diabetic group. In addition, the thickness of the carotid walls had increased less in the intensively treated group during the 5 years than in the conventionally treated group. "This finding strongly
suggests that atherosclerosis progressed more slowly in the intensively treated group," said Genuth.

Carotid thickening was also linked to known cardiovascular risk factors including age, higher systolic blood pressure, smoking, low-density-to-high-density cholesterol ratio, and urinary albumin. After adjustment for these factors, the study found that the differences in carotid wall thickness between the two groups were due to the differences in blood glucose levels during the original trial.

"The risk of heart disease is about 10 times higher in people with type 1 diabetes than in people without diabetes, but it was unclear to what extent blood glucose contributed to the development of heart disease," said David Nathan, MD, the study’s lead author. "Now we know that intensively controlled glucose significantly reduces the atherosclerosis underlying heart disease just as it reduces damage to the eyes, nerves, and kidneys in people with type1 diabetes. What's striking is that the benefits of intensive control persisted despite a gradual rise in the HbA1c levels of the intensively treated group during the 5 years after [the original trial] ended."

"For many people, diabetes is difficult to manage with today's tools. Every new finding about the importance of blood glucose control in preventing complications heightens our determination to foster research that results in new therapies that take the burden off the patient," said Judith Fradkin, MD, of the National Institutes of Health.

About 1 million Americans have type 1 diabetes mellitus. Type 1 disease results from immune-mediated attack on insulin-producing cells, and initial presentation is usually during childhood or early adulthood (under age 30 years).