News & Research

    University of Utah, Salt Lake City, Utah

Metabolic syndrome and peripheral neuropathy: a lifestyle intervention study.

General Research Subject: Type 2 Diabetes

Focus: Complications\Neuropathy, Exercise\Human, Nutrition-Clinical

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2009

Project End Date: December 31, 2011

Research Description

Metabolic Syndrome is the grouping of obesity, prediabetes or diabetes, high blood pressure and abnormal lipids.  The Syndrome increases risk of nerve damage in diabetes.  Once nerve damage starts it may be irreversible.  Therefore early treatment is desirable.  The impaired glucose tolerance (prediabetes) neuropathy study demonstrated that diet and exercise resulted in improved nerve function using a skin biopsy to count the nerves in the skin.  This improvement lasted one year before the nerve numbers again started to decline.  Nerve damage is partially compensated for by nerve re-growth.   Treatments may either slow damage or increase re-growth.  Re-growth may be measured by applying capsaicin, a medicine used for pain, to the skin for 48 hours.  This damages the tips of the nerves in the skin.  Several small punch biopsies may be performed over several months to measure the rate of nerve re-growth.  It is hypothesized that aggressive diet and exercise treatment will result in improvement in the ability of nerves to re-grow.  This study will compare nerve re-growth rates between normal subjects and a group with Metabolic Syndrome, 24 without diabetes and 30 with diabetes.  The ability of diet and exercise to improve nerve re-growth will be determined by re- measuring nerve re-growth rate after one year of treatment.  A positive study will provide strong evidence that Metabolic Syndrome increases the risk for neuropathy by impairing the nerves' ability to heal.  It would also indicate that diet and exercise may prevent nerve damage, and would support further treatment studies.

Reseacher Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes? 

Diabetic neuropathy is among the most costly complications of diabetes and represents a major cause of disability due to foot ulceration and amputation, pain, and gait instability. Once nerve damage starts it may be irreversible.  Therefore early treatment is desirable. The Impaired Glucose Tolerance (prediabetes) Neuropathy Study demonstrated that diet and exercise resulted in improved nerve function using a skin biopsy to count the nerve fibers in the skin.  This improvement lasted one year before the nerve fiber numbers again started to decline.  Nerve damage is partially compensated for by nerve re-growth.   Treatments may either slow damage or increase re-growth.  Re-growth may be measured by applying capsaicin, a medicine used for pain, to the skin for 48 hours.  This temporarily damages the tips of the nerves, causing them to die back from the surface of  the skin.  Over the next several months, nerves grow back into the skin.  Small punch biopsies may be performed at monthly intervals to measure this nerve re-growth.

Metabolic Syndrome is the grouping of obesity, prediabetes or diabetes, high blood pressure and abnormal lipids.  The Syndrome increases risk of nerve damage in diabetes. We hypothesize that aggressive diet and exercise treatment will result in improvement in the ability of nerves to re-grow.  This study will compare nerve re-growth rates between normal subjects and two groups with Metabolic Syndrome; 24 subjects without diabetes and 30 with diabetes.  The ability of diet and exercise to improve nerve re-growth will be determined by re- measuring nerve re-growth rate after one year of treatment.  A positive study will provide strong evidence that Metabolic Syndrome increases the risk for neuropathy by impairing the nerves' ability to heal.  It would also indicate that diet and exercise may prevent nerve damage, and would support further treatment studies.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

Over 50% of diabetic patients develop neuropathy.  Neuropathy is a leading risk factor for foot ulceration and is the leading cause of diabetes-related hospital admissions and leg amputations.  A number of pharmacologic treatments have shown promise in preclinical models, but have failed to work in human studies.  The observation that aggressive diet and exercise intervention results in short term improvement in peripheral neuropathy associated with prediabetes is encouraging.  This project will help to answer why this intervention worked.  We hypothesize that Metabolic Syndrome, particularly obesity and abnormal lipids (cholesterol and triglycerides), reduces the ability of nerve to regenerate after injury (such as that induced by diabetes), and that aggressive lifestyle treatment will improve this ability.  If this were true, it would support routine use of similar interventions in a clinical setting and would also direct us towards new potential treatments and research studies regarding disease mechanism.  The ultimate goal is to develop better preventative and treatment strategies for neuropathy in order to prevent its long term complications including chronic pain, foot ulceration and amputation.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts? 

I see a great many patients with neuropathy.  Many have diabetes and many more have Metabolic Syndrome without diabetes.  At present, we can offer treatment for diabetes, pain management, and good foot care, but we do not have any specific therapies for treatment of neuropathy.  I am committed to ease the suffering of my patients and to try to prevent neuropathy from affecting future diabetic patients.  This award will play a very important role in our research effort as it will allow us to begin to examine factors that influence the nerve's ability to respond to the metabolic stress of diabetes.  We are very hopeful it will lead us towards better ways of preventing neuropathy and treating patients who are developing early diabetic neuropathy.

In what direction do you see the future of diabetes research going? 

Now is an exciting time for researchers interested in diabetic neuropathy.  Our understanding of the basic mechanisms underlying diabetes-induced nerve damage is improving rapidly.  For example, we now recognize the important roles of mitochondrial injury, oxidative stress and damage to the lining of small blood vessels.  We are developing very good tools to diagnose the first stages of neuropathy and to test promising new therapies.  Our work, and that of others, suggests that obesity may be a very important unifying problem underling neuropathy.  I anticipate that our understanding of how obesity contributes to development of diabetic neuropathy will lead to promising new therapeutic approaches in the coming years.  I expect our focus will gradually shift from treatment of well established diabetic neuropathy to screening and treating patients as they first develop symptoms of neuropathy. An ideal goal of this research would be to develop successful prevention strategies.