In a study funded by the National Institute of Diabetes and Digestive and Kidney Diseases, researchers built upon previous research conducted over the last decade establishing evidence that dyslipidemia and obesity increase the risk of developing neuropathy but has not answered why these factors contribute to the pathology.
The study results were published in the Annals of Clinical and Translational Neurology, revealing that participants with high scores for diabetic neuropathy had changes in lipids reflecting impaired energy metabolism.
Senior author of the study, Eva L. Feldman, MD, PhD, director of the NeuroNetwork for Emerging Therapies at Michigan Medicine, James W. Albers Distinguished Professor at University of Michigan, Russell N. DeJong professor of neurology, and colleagues embarked on an effort to establish the relationship between abnormal lipids and the neuropathic condition with which they seem to be associated.
“As we learn more about the relationship between serum lipid species and neuropathy, it will open up the possibility of targeted therapeutic treatment, both with drugs and lifestyle interventions,” Dr. Feldman stated, adding, “Our findings support the concept that unsaturated healthy fats are a better source of energy for nerves that highly saturated fats. We strongly recommend a Mediterranean-type diet to maintain a healthy nervous system.”
The authors also revealed that conventional lipid-lowering drugs that work through pathways that synthesize cholesterol and apoproteins (e.g., fenofibrates and statins) may be ineffective in delaying the onset or treating neuropathy. They wrote, “This study underscores a possible need for therapeutics that optimize fatty acid metabolism and enhance mitochondrial beta-oxidation.”
Using a retrospective cohort study to test their hypothesis that abnormal lipid profiles may be early indicators of future neuropathy, the team examined the lipid profiles of 69 subjects who were members of the Gila River Indian community. The subjects were comprised of 52 females and 17 males with a mean age of 45 years (standard deviation, 9 years) who were diagnosed with type 2 diabetes but 10 years before they received a neuropathy assessment.
Utilizing stored serum samples and neuropathy assessment reported 10 years later using the combined Michigan Neuropathy Screening Instrument (MNSI) examination and questionnaire scores allowed subjects to be divided into those with and without neuropathy (high MNSI index score >2.5407 vs. low MNSI index score ≤2.5407, respectively). Although there were variations detected that were independent of covariates, they detected a specific signaling dysfunction in a critical beta-oxidation pathway—a pathway that converts lipids into sources of nerve energy, and when this pathway is impaired, results in nerve damage leading to neuropathy.
The authors concluded that the differences in circulating acylcarnitines, free fatty acids, phosphatidylcholines, and lysophosphatidylcholines 10 years prior to neuropathy assessment are associated with neuropathy status in type 2 diabetes. They noted that “further research validating and delineating the relationship of serum lipid species to neuropathy in preclinical models could enhance our understanding of pathogenesis and open avenues for targeted therapeutic development.”
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