DCCT/EDIC 30 years later: Positive effects of intensive therapy confirmed in type 1 diabetes
CHICAGO — Thirty years of combined data from the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications study demonstrate that intensive insulin therapy is the best option for patients with type 1 diabetes, as evidenced by a 50% reduction in disease-related complications.
“We are very excited by the long-term results of these studies,” David M. Nathan, MD, director of the Massachusetts General Hospital Diabetes Center and co-chair of the studies, said during a press conference here. “What we knew about intensive insulin therapy before 1993 was that it caused hypoglycemia that we were concerned about. What surprised us most by the DCCT results in 1993 was that the magnitude of the effects was far greater than anyone ever anticipated. However, the demonstrated effects were on the early stages of complications. We now have compelling data that intensive therapy prevents or delays the advanced stages of diabetes complications.”
David M. Nathan
The Diabetes Control and Complications Trial (DCCT) began in 1982 to answer the question of why people with type 1 diabetes have complications, and how those complications can be prevented or delayed, according to Nathan. After 10 years of intensive therapy aimed at lowering glucose levels to as close to normal as possible with frequent insulin injections or pump therapy guided by frequent self-monitoring of blood glucose, patients in the DCCT experienced a reduction in complications compared with conventionally treated participants.
Many questions remained unanswered by DCCT, like whether intensive therapy could prevent kidney dysfunction or improve serious eye outcomes and cardiovascular risk, so researchers continued the study in an observational mode for 20 years, titled Epidemiology of Diabetes Interventions and Complications (EDIC).
Here at the ADA Scientific Sessions, researchers discussed their findings from both studies.
Effects on kidney disease
Long-term results of the DCCT/EDIC demonstrate that intensive therapy decreased the risk for kidney dysfunction by 50%, according to a press release. Ian de Boer, MD, MS, EDIC investigator and associate professor of medicine in the division of nephropathy at the University of Washington, said intensive therapy reduced the risk for microalbuminuria and macroalbuminuria during DCCT and through the first 8 years of EDIC follow-up.
Ian de Boer
“New data on albuminuria … show that the sustained effects continued to last through 18 years of EDIC follow-up, with continued separation in incidence of microalbuminuria and macroalbuminuria through the whole period of time,” he said. “The kidney findings speak volumes to the long-term benefits of intensive therapy. It really demonstrates that intensive therapy can have sustained long-term impacts on many manifestations of this microvascular disease.” de Boer also spoke about hypertension, citing the incidence as greater than 50% than 20 years after randomization in the DCCT. According to data, intensive therapy reduced the incidence by about 20% over this period of time. Additionally, a review of DCCT/EDIC data in a 2011 issue of New England Journal of Medicine demonstrates that intensive therapy reduced the risk for impaired glomerular filtration rate by 50%, he said.
John Lachin, ScD, the principal investigator of the DCCT/EDIC Coordinating Center at The George Washington University in Washington, D.C., provided an update on CVD throughout the course of the studies.
In particular, Lachin focused on results published in the New England Journal of Medicine in 2005. These data linked intensive therapy with about a 57% reduction in the risk for major CVD events during the first 11 years of EDIC combined with the 10 years of DCCT.
“It turns out that those treatment effects were almost all explained by differences in level of HbA1c in the former intensive treatment group during the DCCT,” Lachin, who is professor of biostatistics and epidemiology at The George Washington University School of Public Health and Public Health Services, said at a press conference.
He noted that the reduction in microalbuminuria with intensive therapy played a role, but it did not explain all of the difference between treatment groups with respect to CVD.
“Importantly, the risk reduction in the former intensive treatment group, even though we’ve not published this, has persisted through 2012,” Lachin said. “The original risk reductions associated with intensive therapy have persisted in terms of overall risk of cardiovascular disease.”
Another important outcome is mortality, Lachin said, noting that data on mortality in the cohort over 30 years will be submitted for publication soon.
In terms of diabetic eye disease, Lloyd Aiello, MD, a DCCT/EDIC investigator at the Joslin Diabetes Center in Boston, Mass., highlighted the 50% reduction in the severe stages of diabetic eye disease as well as the need for ocular surgery and procedures in the original intensive therapy group.
“Although we have means of treating severe eye disease to prevent vision loss, it is always better to reduce its development in the first place to avoid the need for expensive and only partly effective late-stage therapies,” Aiello said in a press release. “Intensive diabetes therapy effectively accomplishes this goal.”
Almost as impressive as the actual data is the length of follow-up, Judith Fradkin, MD, director of the division of diabetes, endocrinology and metabolic diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, said during the press conference. Ninety-five percent of the surviving patients who continue to participate after 30 years, she noted, which is unprecedented.
“The reason for this is that patients have benefited,” Fradkin said. “This also demonstrates the importance of continued follow-up and long-term results from interventions in diabetes,” she said. “Diabetes is a lifelong disease. By following these participants for 3 decades, instead of showing what a drug or therapy does over 6 months or 1 year, what matters to people is what’s going to happen over the course of a life, both in terms of the effect of the therapy and also the course of type 1 diabetes in today’s world with contemporary therapy.”
Watch an exclusive video interview with David M. Nathan, MD, on the results of the DCCT/EDIC and an exclusive video interview with Judith Fradkin, MD, on the impact that DCCT/EDIC has had on diabetes management. – by Stacey L. Adams and Melissa Foster
For more information:
Genuth SM. DCCT/EDIC 30th Anniversary Symposium — Contributions and Progress. Presented at: ADA Scientific Sessions; June 21-25, 2013; Chicago.