Intensive diabetes control yields less nerve damage years later

---

Orlando, FL (June 7, 2004) -- New research findings have shown that tight control of type 1 diabetes pays off in reduced rates of nerve damage years later -- when control has become less intense -- possibly due to mechanisms beyond blood glucose levels alone, according to a report here today at the American Diabetes Association's 64th Annual Scientific Sessions.

"People who were treated with intensive therapy to try to keep their blood glucose levels as close to normal as possible for an average of six years continue to demonstrate a lower risk for developing neuropathy, compared to those who were never treated with such intensive therapy, even eight years after the period of intensive therapy ended,â€ý"said Catherine L. Martin, M.S., Study Coordinator for DCCT/EDIC at University of Michigan at Ann Arbor, in a recent interview.

Those who had previously been on intensive therapy were about one-third less likely to develop nerve damage years later, even though their control had become less intense. "The take-home message is that good glucose control should be started as early as possible," said Ms. Martin.

The Diabetes Control and Complications Trial (DCCT), initiated 20 years ago, involved 1,441 people in a comparison of intensive vs. conventional control. Initial results, reported in 1993, demonstrated 39 to 76 percent reductions in complications such as retinopathy, neuropathy and nephropathy. Most participants enrolled in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) observation study, involving an annual assessment for the past eight years, which was the basis of today's report.

More than 18 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease and amputations. It is the fifth leading cause of death by disease in the U.S.

Some one million Americans have type 1 diabetes, an immune-mediated disease that leads to destruction of the insulin-producing beta cells in the pancreas and the need for daily insulin injections throughout life. Type 1 usually arises in children or young adults.

Conventional control during the DCCT required only one or two injections and blood checks daily, with the aim of preventing overt diabetes symptoms, and typically yields levels of A1C, a measure of long-term glucose control, of nine percent or more. Intensive control to bring A1C levels as close to normal as possible (

In the EDIC study, it was observed that the A1C levels of the former intensive and conventional control groups have converged over the past eight years. That is, once out from under the close monitoring of DCCT, the A1Cs of the former intensive control participants have risen from 7.2 percent at the end of the DCCT to 7.98 percent. In contrast, A1C levels of the former conventional control group, once taught intensive control, dropped from 9 to 7.94 percent. Thus, there has been very little difference in A1C levels over the past eight years, in contrast to the significant difference in the initial study years.

Nonetheless, a paper presented here today reported that those previously on intensive control continue to have significantly less neuropathy than those who were on conventional control. "At eight years of follow-up post-DCCT, the relative risk for neuropathy is 0.64 in those who were previously on intensive control compared to those who were on conventional control," said Ms. Martin. "Thus, long-term benefits continue to be shown despite a convergence of A1Cs."

At last year's ADA meeting, it was reported that those previously on intensive control had significantly less calcification in their coronary arteries (a marker of atherosclerosis -- macrovascular disease), and markedly reduced progression of microvascular disease, than those who were on conventional control.

While the mechanism underlying the delayed neuropathy benefits remains unknown, the researchers believe it may be due to a cascade of metabolic effects triggered by high glucose levels or, perhaps, an "imprinting" of metabolic memory, or other unknown causes.

These results have prompted medical scientists to start thinking in greater detail about the possible mechanisms underlying this sustained effect of early intensive blood glucose control -- the late effects shown by EDIC.

"These findings raise intriguing questions for which no answers have yet been reached, but they solidify the need to aggressively manage diabetes," emphasized Ms. Martin.

"DCCT/EDIC could not have produced its ground-breaking results, which have changed the way diabetes care is practiced, without the terrific dedication of the more than 1,400 study volunteers -- people with diabetes -- some of whom have been involved for up to 21 years, as well as the persistence of the investigators," said Ms. Martin.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.