The study, published in the February issue of the journal Diabetes Care, involved 1,441 people with Type 1 diabetes, also known as juvenile diabetes.

Although patients with the more common Type 2 form of diabetes were not involved, the results may have implications for the 18 million Americans with Type 2 diabetes.

Two-thirds of all people with diabetes have some degree of nerve problems, or neuropathy, related to their diabetes.

The most common sign is numbness or pain in the feet and legs, which can progress over time to cause disability. Neuropathy plays a major role in 80,000 foot and leg amputations in American diabetics each year.

“This is an exciting finding that adds credence to the idea of metabolic memory, or the concept that there can be a durable effect from early and sustained efforts to keep blood sugar low,” says senior author Eva Feldman, M.D., Ph.D., the DeJong Professor of Neurology at the University of Michigan Medical School and director of the U-M Neuropathy Center.

 “It suggests that good glucose control clearly protects patients over the long term.”

The new study marks the first time that tight blood sugar control has been shown to have a long-term effect on the chance that a person with diabetes will develop neuropathy.

Similar findings have been made for two other frequent complications of diabetes, retinopathy (eye disease) and nephropathy (kidney disease).

The new findings come from the Epidemiology of Diabetes Intervention and Complications (EDIC) study that grew out of the national Diabetes Control and Complications Trial (DCCT).

Funded by the National Institute of Diabetes and Digestive & Kidney Diseases, the DCCT began in the 1980s by randomly assigning people with Type 1 diabetes to either tight blood-sugar control using three insulin injections per day or an insulin pump, or to more typical blood sugar control for the time, using one to two insulin injections a day.

The latter group was later encouraged to adopt tight blood sugar control, and the EDIC study tracked all patients’ health.

The new paper reports results from eight years of neuropathy assessments under the EDIC study, among 1,441 DCCT participants who had no symptoms or signs of neuropathy at the end of the DCCT.

The symptoms and signs were assessed using a standardized questionnaire developed and validated by U-M researchers from the Michigan Diabetes Research and Training Center. Called the Michigan Neuropathy Screening Instrument, the questionnaire is completed by both patients — who report symptoms such as tingling, pain, numbness, and sensitivity — and by physicians, who complete a physical examination of the patients’ feet, including sensitivity to touch and vibration, and the presence of calluses and sores that the patients might not be able to feel because of nerve damage.

Such foot problems can become infected and lead to open wounds that can be hard to heal because of other aspects of diabetes.

Unhealed infections, if bad enough, can lead to decisions to amputate toes, feet and legs. This “domino effect” starting with neuropathy and leading to infection and amputation is the reason that current guidelines call for people with diabetes to have annual foot exams.

Feldman, who led the analysis along with research nurse Catherine Martin, M.S., notes that the study looked at the percentage of participants who had any positive sign of neuropathy on their questionnaire or their foot examination each year of the EDIC study, and then separated them according to which DCCT group (tight glucose control or regular control) they had been in.

This allowed them to track the impact of prior tight glucose control, even though all the participants were encouraged to control their blood sugar tightly once they entered the EDIC phase of the project.

Test results taken each year show that the two groups achieved very similar blood-sugar control in the later years of the EDIC study, with levels of a measure called A1C around 8 percent for both groups.

After the first year, 28 percent of the regular-control patients showed signs of neuropathy on their physical exam, though only 4.7 percent reported symptoms on their questionnaires.

By contrast, 17.8 percent of the tight-control patients had neuropathy signs on their foot exams, and 1.8 percent reported symptoms. The difference between the two groups was highly statistically significant.

Over time, the difference between the two groups continued to be significant, although the percentage of both groups that showed signs or reported symptoms of neuropathy increased over time.

By the end of the eighth year of follow-up, almost 7 percent of the participants who had been in the regular-control group reported feeling symptoms of neuropathy, compared with about 3.5 percent of the tight-control patients.

And at the end of eight years, more than 26 percent of regular-control participants had signs of neuropathy on their physical exam, compared with just over 20 percent of tight-control participants.

The researchers calculated statistical likelihoods for these measures. In all, participants who had begun with tight blood-sugar control and stuck with it were 51 percent less likely to report symptoms of neuropathy, and 43 percent less likely to show signs of it, than those who had started out with regular blood-sugar control and then gone to tight control.

There were also differences between the two groups in the incidence of open sores requiring medical or surgical treatment, and in incidence of amputation.

In all, says Feldman, the results reinforce a key message for all of today’s diabetes patients, though Type 2 diabetics tend to have other health problems that can interfere with the protective effects of tight sugar control.

 That message: Check your blood sugar levels regularly, and take steps to keep them under tight control, with few extremes of low or high sugar.

Meanwhile, Feldman and others are searching for the reason why nerve cells are damaged by high blood sugar, and why it might be more beneficial to start tight glucose control early. The EDIC sites have received an NIDDK grant to make more precise measurements of neuropathy signs among EDIC participants.

 And U-M is offering five diabetic neuropathy clinical trials for different types of patients. For more on participating in such research, patients can visit www.med.umich.edu/pfund,  the Program for Understanding Neurological Diseases. Reference: Diabetes Care, Vol 29, No. 2, pp. 340-344.