Lipid-lowering Drugs Protect Against Peripheral Diabetic Neuropathy
source: Diabetes Today
Lipid-lowering Drugs Protect Against Peripheral Diabetic Neuropathy
Australian Study Shows Statins and Fibrates Prevent One of Most Common
Diabetes Complications
Chicago, IL (June 22, 2007) - A major epidemiological study conducted over
eight years in Australia has shown that two classes of lipid-lowering
drugs - statins and fibrates - significantly lower the risk of developing
nerve damage known as peripheral sensory diabetic neuropathy, according to a
report presented today at the American Diabetes Association’s 67th Annual
Scientific Sessions.
"Statins and fibrates, drugs already highly recommended for people with type
2 diabetes to help prevent heart attacks, now also appear to help prevent
one form of diabetic nerve damage called peripheral neuropathy - a common
complication of diabetes," said Timothy Davis, MD, PhD, Professor of
Medicine, at the University of Western Australia, and principal investigator
of the study, in a recent interview. "Statins or fibrates reduced the risk
of developing peripheral neuropathy by 35% or 48%, respectively, although
these should be considered comparable risk reductions because of the wide
confidence intervals." A correct estimate falls into a statistical range
called a confidence interval, and the range in this instance means that the
two estimates are indistinguishable, statistically-speaking.
Nearly 21 million Americans have diabetes, a group of serious diseases
characterized by high blood glucose levels that result from defects in the
body’s ability to produce and/or use insulin. Diabetes can lead to severely
debilitating or fatal complications, such as heart disease, blindness,
kidney disease, nerve damage, and amputations. It is the fifth leading cause
of death by disease in the U.S.
All of the study participants had type 2 diabetes, which involves insulin
resistance - the body’s inability to properly use its own insulin. Type 2
used to occur mainly in adults who were overweight and ages 40 and older.
Now, as more children and adolescents become overweight and inactive, type 2
diabetes is occurring more often in young people.
METHODOLOGY AND FINDINGS The researchers assessed the relationship between
lipid-lowering therapy and the prevalence and incidence of peripheral
neuropathy, based on scoring on the Michigan Neuropathy Screening Instrument
?-one of the most sensitive and specific tools for screening for the
condition ? in a large representative cohort of adults. Prevalence measures
how much of a disease or condition there is in a population at a particular
point in time. Incidence measures the rate of occurrence of new cases of a
disease or condition.
The cross-sectional sample was comprised of all 1,294 of those recruited to
the Fremantle Diabetes Study between 1993 and 1996.
At their entrance into the study, the participants average age was 64 years,
with their diabetes diagnosed four years previously, 48.8% were male, and
30.9% had neuropathy. Fibrates and statins were used by 3.5% and 6.8%,
respectively.
Older age, longer diabetes duration, central adiposity, increasing height,
higher fasting plasma glucose, higher systolic blood pressure, higher
urinary albumin to creatinine ratios, and indigenous racial background were
all independently associated with prevalent peripheral neuropathy at
baseline, while use of fibrates was associated with a 70% reduction in
neuropathy prevalence.
The longitudinal sub-group was comprised of 531 people who had attended six
comprehensive annual health assessments by November 2001. Use of fibrates
and statins increased to 10.4% and 36.5%, respectively, during the five
years of follow-up. The results were controlled for potential confounding
variables, including changes in A1C levels, a measure of long-term blood
glucose control.
Time to development of newly diagnosed peripheral neuropathy in the
longitudinal sub-group showed that fibrates and statins reduced neuropathy
risk by 48% and 35% respectively. Further, they may have independent action.
"In our analysis, the beneficial effects of the drugs were independent of
each other and they may work through different mechanisms," said Dr. Davis.
"It?s just a hypothesis, but taking both drugs may yield greater benefit
than taking either drug alone."
At the outset, in the cross-sectional study, the fibrate participants were
using gemfibrozil, and the statins in use were atorvastatin, simvastatin and
pravastatin. At the end of the longitudinal study, gemfibrozil continued to
be the primary fibrate used, although some had begun to use fenofibrate. By
then atorvastatin was the predominant statin, although simvastatin and
pravastatin also continued to be in use.
"We believe these benefits are class effects of these drugs," said Dr.
Davis. While many mechanisms have been proposed, their mechanism of action
in neuropathy remains unknown. The leading theory for statins seems to be a
reduction of both inflammation and oxidative stress.
"People with diabetes should not shy away from taking these drugs for both
heart and neuropathy benefits," he said. "Whether a fibrate or statin should
be taken is never an easy choice, but a statin is usually the first line
drug because of the strong evidence of cardiovascular disease prevention
benefits."
Co- authors with Dr. Davis were Bu Yeap, MD, PhD, David G. Bruce, MD, PhD,
and Wendy A. Davis, PhD, all of the University of Western Australia.
The American Diabetes Association is the nation’s leading voluntary health
organization supporting diabetes research, information and advocacy. Founded
in 1940, the Association has offices in every region of the country,
providing services to hundreds of communities.