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Diabetics Who Control Blood Sugar Today Are More Likely to Have Healthy Feet
and Nerves Tomorrow
Effects of tight glucose control seen years later in diabetic neuropathy
study

ANN ARBOR, M.I. -- March 10, 2006 -- People with diabetes who keep their
blood sugar in check today will probably have a far lower chance of
developing foot pain or other nerve damage tomorrow, according to new
research results from a national study.

In fact, the study shows that the positive effects of tight blood glucose
control can be seen more than a decade later. At the end of the study
period, patients who had controlled their blood sugar tightly ever since the
start of the study were 51% less likely to have nerve problems than patients
who started the study at the same time but did not have the initial 5 year
period of intensive blood sugar control.

The study, published in the February issue of the journal Diabetes Care,
involved 1441 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,
MD, PhD, 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 1441 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,
MS, 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% for both groups.

After the first year, 28% of the regular-control patients showed signs of
neuropathy on their physical exam, though only 4.7% reported symptoms on
their questionnaires. By contrast, 17.8% of the tight-control patients had
neuropathy signs on their foot exams, and 1.8% 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% of the participants who had been in the
regular-control group reported feeling symptoms of neuropathy, compared with
about 3.5% of the tight-control patients. And at the end of eight years,
more than 26% of regular-control participants had signs of neuropathy on
their physical exam, compared with just over 20% 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% less likely to report symptoms of neuropathy, and 43% 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.

REFERENCE:
Diabetes Care, Vol 29, No. 2, pp. 340-344.

SOURCE: University of Michigan Health System