Issue 212 Item 6 Tight Glucose Control For DCCT Provides Benefits 15 Years Later

Continued follow up with the participants in the Diabetes Complications and Control Trial (DCCT) suggest that tight control has significant benefits even in the long term. Eight years after the DCCT ended, patients in the original tight glucose control group had significantly lower levels of diabetic neuropathy, retinopathy, and nephropathy than patients in the original conventional therapy group. The benefits for early intensive therapy persisted even though patients in the former conventional treatment group were given a crash-course in intensive diabetes management at the end of the DCCT.

Patients in the intensive treatment group saw later benefits from their early efforts despite the fact that their A1c levels, which were significantly lower than those of control patients at the end of DCCT, had converged with those of the conventional therapy group eight years later.

Results of the follow-up trial, called the Epidemiology of Diabetes Interventions and Complications (EDIC) study.
Catherine L. Martin, MS, APRN, clinical care coordinator at the Michigan Diabetes Research and Training Center at the University of Michigan in Ann Arbor stated that, "We don’t yet know how long this trend is going to last. I think we were all stunned when we started seeing these trends that the HbA1c [levels] are predictive early in the game."

Although the A1c levels were significantly different between the two groups at the end of the DCCT (7.2% for the intensive therapy group vs. 9.1% for the conventional therapy group), they had converged by year 8 of the EDIC trial, at 7.98% and 7.94%, respectively.

"I think some of the convergence is due to a withdrawal of the intensity with which we follow people up," Ms. Martin stated. "In DCCT, people were provided with all their supplies, they got weekly phone calls, they got monthly visits. Now care has been turned over to others and that intensity of follow-up does not exist, and so I think we’ve seen a regression to the mean."

Despite the convergence, which demonstrated a gradual loss of glycemic control among those in the intensive therapy group, the EDIC investigators found that former good habits translated into a relative risk reduction for neuropathy of 36% in subjects based on the MNSI examination, and by 50% based on the questionnaire.

"This persistent beneficial effect of a prior period of glycemic control has also been reported for retinopathy and nephropathy," Ms. Martin said in her presentation.

Rury R. Holman, FRCP, professor of diabetic medicine at the University of Oxford in the U.K., was not involved in EDIC study, but he saw similar results among patients with type 2 diabetes as cochair of the United Kingdom Prospective Diabetes Study (UKPDS).

"What we see is the same as we saw in the type 2 [diabetes] patients in UKPDS, which is there seems to be a continued protection from risk," Dr. Holman said. "We called it a ‘legacy effect,’ they call it ‘metabolic memory.’ It’s partly statistical in that the groups are already at separate levels of risk, but I think both their analyses and ours suggest that the degree of risk protection is maintained. It probably takes a considerable amount of time for those benefits to be lost."

Dr. Holman added, "What’s interesting today is that they’re still seeing it at seven and eight years, and that to me is interesting because that isn’t just reflecting the time scale or the separation initially."
ADA 64th Annual Scientific Sessions: Abstract 244-OR. Presented June 7, 2004.

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