Tight Glucose Control May Provide Long-term Benefits in Diabetics

Neil Osterweil

Medscape Medical News 2004. © 2004 Medscape

June 9, 2004 (Orlando) — Tight glucose control can have significant benefits in the long term, suggest results of a new study that has continued to follow the participants in the Diabetes Control and Complications Trial (DCCT).

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, were presented at an oral abstracts session here at the 64th annual meeting of the American Diabetes Association by coinvestigator Catherine L. Martin, MS, APRN, clinical care coordinator at the Michigan Diabetes Research and Training Center at the University of Michigan in Ann Arbor.

"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," Ms. Martin said in an interview with Medscape.

The EDIC trial enrolled 1,388 patients (96% of the original DCCT cohort). Patients were assessed annually using the Michigan Neuropathy Screening Instrument (MNSI), which consists of a self-administered symptom questionnaire, and foot examination performed by the study coordinator or a physician. The foot examination included visual inspection as well as grading of ankle reflexes and monofilament and vibratory testing at the great toe. Patients were considered to have diabetic neuropathy when they had questionnaire scores greater than 6 of 15 and/or 3 or more (of 10) positive examination scores.

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 told Medscape. "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).

In an interview with Medscape, Dr. Holman said that while the benefits of tight glucose are well known, the persistence of the effect comes as a surprise.

"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."

The EDIC study was funded by the National Institute of Diabetes, Digestive, and Kidney Diseases.

ADA 64th Annual Scientific Sessions: Abstract 244-OR. Presented June 7, 2004.

Reviewed by Gary D. Vogin, MD