DCCT at 18 years: Intensive HbA1c control still yielding CV benefits

Miriam E Tucker

June 24, 2013


June 23, 2013

Chicago, IL - Dramatic reductions in type 1 diabetes complications, including cardiovascular events, achieved with intensive glycemic control in the landmark Diabetes Control and Complications Trial (DCCT) are still being seen—although to a somewhat lesser degree—nearly two decades after the study's end [1].

After 18 years, the overall prevalence of diabetes complications is 50% lower among the type 1 diabetes patients in the DCCT who were randomized to intensive glucose control compared with those who received conventional treatment, despite the fact that HbA1c levels are no longer different between the two study groups.

The findings were presented here at the American Diabetes Association (ADA) 2013 Scientific Sessions. Even after so many years, "the message is exactly the same," DCCT/EDIC biostatistician Dr John M Lachin (George Washington University, Rockville, MD) said in an interview. "The HbA1c matters today, tomorrow, and for many, many years to come. It matters."

EDIC investigates "metabolic memory"

The new data come from the DCCT's long-term follow-up study Epidemiology of Diabetes Interventions and Complications (EDIC), which began in 1994, the year after DCCT ended. Glycemic control in the two groups became roughly the same soon after patients went back to their communities for care, so EDIC is measuring the ongoing impact of glycemic control in the initial study's 10 years, a phenomenon investigators have dubbed "metabolic memory."

Previously reported end points of retinopathy, nephropathy, neuropathy, and cardiovascular disease continue to be reduced among those originally in the intensive-treatment group, albeit to a lesser degree than in previous EDIC analyses in 2000 [2].

The investigators are also looking at mortality in EDIC, with results under embargo, as they are due to be published soon. However, Lachin did divulge that there is no increased mortality among the intensive-treatment group, a phenomenon that has been seen in some trials involving patients with type 2 diabetes.

EDIC coordinating center principal investigator, Dr Rose Gubitosi-Klug (Case Western Reserve University School of Medicine, Cleveland, OH), said: "In some ways, it's surprising how it's gone on this long. [The original DCCT investigators] expected the effect to wane after 10 or 12 years. But here we are at 18 years, and we still have significant risk reduction. Although it's starting to decrease over time, there's still a significant reduction. It's fantastic."

The lesson from all of it, said Gubitosi-Klug, is: "Start intensive diabetes management as soon as safely possible."

Clinically meaningful CVD reductions persist

The original DCCT involved 1441 patients with type 1 diabetes. After DCCT ended, patients who had been in the conventional-treatment group were instructed in intensive glycemic control. Their average HbA1c levels dropped to about 8%. At the same time, control worsened in the original intensive-control group to about 8%. That level has remained relatively unchanged during EDIC.

In the original DCCT study, intensive glycemic control—resulting in a mean HbA1c of about 7%—reduced the risk for retinopathy, nephropathy, and neuropathy compared with the conventional-treatment group, whose HbA1c averaged about 9%. At the time DCCT ended, it was too soon to assess CVD outcomes in the still relatively young study population, Lachin explained.

As reported in 2005, however, nine years into EDIC, there was a 42% decrease in any cardiovascular event and a 57% reduced risk for nonfatal heart attack, stroke, or death from cardiovascular causes. Extending those analyses through 2012, those same risk reductions are 33% and 35%, "both still statistically significant and of course clinically meaningful," Lachin observed.

Previously published EDIC analyses have shown benefits of intensive glycemic control in carotid intimal-medial thickness and cardiac function [3], he added.

All the currently monitored end points will continue to be followed, with cardiovascular end points expected to become more prevalent in the now middle-aged study population.

The intensive-treatment group has also enjoyed lasting benefits in terms of neurologic, renal, and retinopathy end points.

Both the DCCT and the EDIC are funded by the US National Institutes of Health . Lachin is a board member of Boehringer Ingelheim, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, and Reata and is a consultant for Andromeda Biotech and Magellan Health Services.


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