The 30-year natural history of type 1 diabetes complications

In one of the most comprehensive, long-term studies to date of the complications associated with type 1 diabetes, researchers at the University of Pittsburgh Graduate School of Public Health (GSPH) discovered that while cases of premature death and a few other complications have declined, rates of other serious diabetes-related disorders such as heart and eye disease have not improved over the past 25 to 30 years.

In the study, published in the May 1 issue of the journal Diabetes, the investigators analyzed long-term complications such as mortality, renal failure and coronary artery disease in 906 type 1 diabetics participating in the Pittsburgh Epidemiology of Diabetes Complications Study, or EDC. The EDC is an ongoing investigation to document long-term complications of type 1 diabetes among juveniles and adolescents who were patients at Children's Hospital of Pittsburgh between 1950 and 1980.

To conduct their analysis, the University of Pittsburgh researchers and their collaborators divided EDC participants into five groups according to the year their diabetes was first diagnosed: 1950-1959, 1960-1964, 1965-1969, 1970-1974 and 1975-1980. The investigators then analyzed lifespan and illness data among the participants for three separate time intervals: 20, 25 and 30 years post-diagnosis.

Their analysis of mortality data showed that for each group, those diagnosed in later years lived longer. Indeed, individuals diagnosed in the 1950s had a five-fold higher rate of early death at 25 years post-diagnosis than those diagnosed in the 1970s. Some morbidity rates also were reduced. For example, kidney-failure rates declined significantly for those diagnosed more recently. At 20 years post-diagnosis, 4 percent of those diagnosed after 1964 developed renal failure compared to 16 percent among those diagnosed in the 1950s. At 30 years post-diagnosis, renal-failure rates had declined from 31 percent in the 1950s to 18 percent in the 1960s.

On the other hand, there were no differences across cohorts for rates of cardiovascular disease events and cardiac intervention procedures. Even when the researchers took into account the fact that revascularization procedures, such as balloon angioplasty and stenting, have become more common than they were in the 1950s and 1960s, their analysis found no differences in cardiovascular disease among the study population at either 20 or 30 years duration. Finally, there were no differences between the groups in rates of kidney dysfunction or proliferative retinopathy, a major cause of blindness in type 1 diabetics, at 20 and 25 years post-diagnosis.

"Doctors have long considered type 1 diabetes a small blood vessel problem, so they have traditionally not focused on the potential large blood vessel complications, such as cardiovascular disease. However, our study suggests that doctors and their patients need to pay more attention to factors that affect the larger blood vessels, such as lipids and blood pressure," explained Georgia Pambianco, M.S., M.P.H., lead study author, who has been a member of the EDC research staff from its inception.

Indeed, although focusing primarily on blood-glucose control has significantly decreased early death in type 1 diabetics, the data from this study suggests these individuals remain significantly burdened with other serious chronic diseases. "We were, in fact, both surprised and disappointed that there were no improvements in cardiovascular and retinopathy disease rates, particularly because other complications improved so dramatically," said Trevor Orchard, M.D., professor of epidemiology, medicine and pediatrics at GSPH and principal investigator of the EDC. "Our data show that focusing solely on blood-glucose control is only postponing, not preventing, some of the more significant complications of this disease."

Dr. Orchard, who also is medical director of the Nutrition Lipid Program at the University of Pittsburgh, said although there have been only a few studies in children on the safety of statins--the lipid lowering drugs--those studies found statins to be relatively safe. "This is certainly a group that could potentially benefit from more aggressive lipid control. In fact, much more focused attention needs to be paid to all cardiovascular risk factors, particularly lipids and blood pressure, and at an earlier age than we have been doing previously. This childhood-onset group is at a higher risk for cardiovascular disease even at early middle age. Waiting until they are adults to treat their lipids is too late."

Ms. Pambianco added that "many of the guidelines currently used for managing type 1 diabetes are derived from what we know about people with type 2 diabetes. We need to recognize that they are two different conditions with different processes involved. Therefore, some of the complications we see in type 2 diabetes do not occur in type 1 and vice versa."

More than 700,000 Americans have type 1 diabetes, an autoimmune disorder in which the body errantly attacks the insulin-producing cells of the pancreas. Type 1 diabetes, which is usually diagnosed in children and young adults, is the leading cause of new cases of blindness among adults aged 20 to 74 years and also is the leading cause of kidney failure in the U.S. Two out of three people with diabetes die from heart disease and stroke, and about 60 percent to 70 percent have mild-to-severe forms of nervous-system damage. Ten times as many people in the U.S. have type 2 diabetes--or adult-onset diabetes--which is most often the result of cells in the body becoming resistant to the effects of insulin. It is most often easier to manage than type 1 diabetes.