Tight Glucose Control in Diabetes Lowers Risk of Atherosclerosis

Strict glucose control in type 1 diabetes reduces the risk of atherosclerosis, a benefit that persists for years, according to a study published in the June 5, 2003 issue of the New England Journal of Medicine.

Since 1993, when the Diabetes Control and Complications Trial (DCCT) ended, researchers have known that intensive glucose control greatly reduces the eye, nerve, and kidney damage of type 1 diabetes. Now, researchers conclude, the benefits of tight control also extend to the heart.

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

The DCCT 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 three insulin injections a day or an insulin pump and frequent self-monitoring of blood glucose. Intensive treatment aimed to keep hemoglobin A1c (HbA1c), which reflects average blood sugar over 2 to 3 months, to as close to normal (6 percent) as possible. Conventional treatment at that time consisted of one or two insulin injections a day with daily urine or blood glucose testing.

After 6? years of the DCCT, HbA1c levels averaged 7 percent in the intensively treated group and 9 percent in the conventionally treated group. When the DCCT ended, those who had been assigned to conventional treatment were encouraged to adopt intensive control and shown how to do it, and researchers began a long-term follow-up study of the participants, called the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

The DCCT could not study atherosclerosis because the participants were relatively young, and heart disease takes years to develop. In 1994-95 and again in 1998-2000, EDIC researchers used ultrasound to measure the thickness of participants' carotid arteries, the two blood vessels in the neck that carry blood from the heart to the brain. Carotid wall thickness reflects the amount of atherosclerosis, or plaque build-up, in the artery: the thicker the arterial wall the greater the risk of later heart attack and stroke.

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. Five years later, however, the participants had thicker arterial walls than those of 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," noted Dr. Genuth.

Carotid thickening was also linked to known cardiovascular risk factors including age, higher systolic blood pressure, smoking, LDL:HDL cholesterol ratio, and urinary albumin (a measure of kidney function). After adjusting 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 DCCT.

"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 Dr. David Nathan of Massachusetts General Hospital, who co-chaired the DCCT/EDIC research group. "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 type 1 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 DCCT 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 Dr. Judith Fradkin, director of the Diabetes, Endocrinology, and Metabolic Diseases Division of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

About 17 million people in the United States have diabetes, the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke. About 1 million have type 1 diabetes. Formerly known as juvenile onset or insulin-dependent diabetes, type 1 diabetes usually begins in children and adults under age 30. It develops when the body's immune system attacks the insulin-producing cells of the pancreas.

Type 2 diabetes accounts for up to 95 percent of all diabetes cases. Most common in adults over age 40, type 2 diabetes affects 6.2 percent of the U.S. population. It is strongly associated with obesity (more than 80 percent of people with type 2 diabetes are overweight), inactivity, family history of diabetes, and racial or ethnic background. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Pacific Islanders are at particularly high risk for type 2 diabetes. The prevalence of type 2 diabetes has tripled in the last 30 years, due in large part to the upsurge in obesity.

DCCT and EDIC were supported by the NIDDK, the National Eye Institute, the National Institute of Neurological Disorders and Stroke, and the National Center for Research Resources, all components of the National Institutes of Health under the Department of Health and Human Services. The studies also received support from Genentech, Inc., through a Cooperative Research and Development Agreement with the NIDDK.