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Triglycerides Implicated in Diabetic Neuropathy

ANN ARBOR, Mich -- May 22, 2009 -- A common blood test for triglycerides may also for the first time allow doctors to predict which patients with diabetes are more likely to develop the serious, common complication of neuropathy.

In a study now online in the journal Diabetes, University of Michigan and Wayne State University researchers analysed data from 427 patients with diabetic neuropathy. The data revealed that patients with elevated triglycerides were significantly more likely to experience worsening neuropathy over a period of 1 year. Other factors, such as higher levels of other lipids or of blood glucose, did not turn out to be significant. The study will appear in print in the journal's July issue.

"In our study, elevated serum triglycerides were the most accurate at predicting nerve fibre loss, compared to all other measures," said study co-author Kelli A. Sullivan, PhD, Assistant Research Professor in Neurology, University of Michigan (U-M) Medical School, Ann Arbor, Michigan.

"These results set the stage for clinicians to be able to address lowering lipid counts with their diabetes patients with neuropathy as vigilantly as they pursue glucose control," said senior study author Eva L. Feldman, MD, PhD, Russell N. DeJong Professor of Neurology, U-M Medical School, Ann Arbor, Michigan.

The researchers examined data from a previous clinical trial of a drug that showed promise for relieving neuropathy. They looked at data from 427 participants who had mild to moderate diabetic neuropathy at the beginning of the 1-year trial. Among other factors, the trial measured myelinated fibre density in a peripheral nerve in the leg in participants over the course of the year. A decline in this density is a prime indicator that neuropathy is worsening.

The new findings are an example of how medical science often looks for one thing and doesn't find it -- the drug trial found that a promising agent turned out to be ineffective for treating neuropathy -- but the data can yield unexpected, useful knowledge about something else.

Realising the trial data held potential clues, the U-M team selected trial participants who had similar characteristics regarding nerve function at the beginning of the study but significantly lower myelinated fibre densities at the end. They used microarray technology not available 15 years ago, when the data was collected.

"We then compared all of the other data concerning lipids and blood glucose. We found that out of all the data collected on these patients, elevated triglycerides [was] the factor that differed the most, when we compared the patients who lost nerve fibres with those who didn't," said Dr. Sullivan.

Elevated triglycerides correlated with the nerve fibre loss independent of disease duration, age, diabetes control, or other variables. With a readily available predictor for nerve damage, physicians and patients can take pro-active steps when interventions can do some good, said Dr. Feldman.

"Aggressive treatment can be very beneficial to patients in terms of their neuropathy," says Feldman, who is also Director of the A. Alfred Taubman Medical Research Institute and Director of the Juvenile Diabetes Research Foundation Center for the Study of Complications in Diabetes at the University of Michigan.

Until now, physicians have lacked an effective way to predict which patients with diabetes are at greatest risk of neuropathy. Most often, the condition becomes evident when irreversible nerve damage has already occurred. Neuropathy is the leading cause of diabetes-related hospital admissions and amputations that are not secondary to trauma.

The new finding adds to an emerging picture of the close connections between cardiovascular disease and diabetes. Elevated triglycerides are one of the most common features of the lipid disorders found in patients with type 2 diabetes, by far the most common form of diabetes, explained study author Rodica Pop-Busui, MD, PhD, Assistant Professor, Metabolism, Endocrinology and Diabetes Division of the Department of Internal Medicine, U-M Medical School, Ann Arbor, Michigan.

"Our findings in this study reinforce the tight links between cardiovascular disease and peripheral neuropathy in patients with diabetes. We demonstrated that the same lipid particles that contribute to the progression of atherosclerosis are also very important players in peripheral nerve fibre loss," said Dr. Pop-Busui.

In addition, the study confirms a growing belief among some diabetes researchers that elevated blood levels of certain lipids, rather than solely elevated glucose, are key in the progression of diabetic neuropathy. The study pinpoints triglycerides as the critical indicator.

Other U-M authors include Timothy D. Wiggin, MS, co-first author; non U-M authors are Anders Sima, MD, Professor of Pathology and Neurology, Wayne State University Medical School, Detroit, Michigan; and Antonino Amato, MD, Sigma-Tau Research, Gaithersburg, Maryland.

The study was funded by the National Institutes of Health, Juvenile Diabetes Research Foundation Center for the Study of Complications in Diabetes, American Diabetes Association, Thomas Foundation, Sigma Tau Research, and the U-M Program for Neurology Research and Discovery.

SOURCE: University of Michigan Health System

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