Journal Article

Elevated Triglycerides Correlate With Progression of Diabetic Neuropathy

Antonino Amato, Kelli A. Sullivan, Timothy D. Wiggin, Anders A.F. Sima, Eva L. Feldman, Rodica Pop-Busui

2009

Overview

Elevated Triglycerides Correlate With Progression of Diabetic Neuropathy Timothy D. Wiggin 1 , Kelli A. Sullivan 1 , Rodica Pop-Busui 2 , Antonino Amato 3 , Anders A.F. Sima 4 and Eva L. Feldman 1 1 Department of Neurology, University of Michigan, Ann Arbor, Michigan; 2 Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan; 3 Sigma-Tau Research, Sigma-Tau Pharmaceuticals, Gaithersburg, Maryland; 4 Departments of Pathology and Neurology, Wayne State University, Detroit, Michigan. Corresponding author: Eva L. Feldman, efeldman{at}umich.edu . T.D.W. and K.A.S. are both first authors and contributed equally to this article. Abstract OBJECTIVE To evaluate mechanisms underlying diabetic neuropathy progression using indexes of sural nerve morphometry obtained from two identical randomized, placebo-controlled clinical trials. RESEARCH DESIGN AND METHODS Sural nerve myelinated fiber density (MFD), nerve conduction velocities (NCVs), vibration perception thresholds, clinical symptom scores, and a visual analog scale for pain were analyzed in participants with diabetic neuropathy. A loss of ≥500 fibers/mm 2 in sural nerve MFD over 52 weeks was defined as progressing diabetic neuropathy, and a MFD loss of ≤100 fibers/mm 2 during the same time interval as nonprogressing diabetic neuropathy. The progressing and nonprogressing cohorts were matched for baseline characteristics using an O'Brien rank-sum and baseline MFD. RESULTS At 52 weeks, the progressing cohort demonstrated a 25% decrease ( P < 0.0001) from baseline in MFD, while the nonprogressing cohort remained unchanged. MFD was not affected by active drug treatment ( P = 0.87), diabetes duration ( P = 0.48), age ( P = 0.11), or BMI ( P = 0.30). Among all variables tested, elevated triglycerides and decreased peroneal motor NCV at baseline significantly correlated with loss of MFD at 52 weeks ( P = 0.04). CONCLUSIONS In this cohort of participants with mild to moderate diabetic neuropathy, elevated triglycerides correlated with MFD loss independent of disease duration, age, diabetes control, or other variables. These data support the evolving concept that hyperlipidemia is instrumental in the progression of diabetic neuropathy. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received December 19, 2008. Accepted April 6, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. © 2009 by the American Diabetes Association.

• Publisher: American Diabetes Association
• Subject: Adult / Aged / Biological and medical sciences / Biopsy / Care and treatment / Clinical trials / Company business management / Data analysis / Diabetes / Diabetes Mellitus, Type 1 - physiopathology / Diabetes Mellitus, Type 2 - physiopathology / Diabetes. Impaired glucose tolerance / Diabetic neuropathies / Diabetic Neuropathies - blood / Diabetic Neuropathies - pathology / Diabetic Neuropathies - physiopathology / Diabetic neuropathy / Disease Progression / Electrophysiology / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Genetic aspects / Glucose metabolism / Glycated Hemoglobin A - metabolism / Humans / Male / Management / Medical sciences / Metabolic disorders / Middle Aged / Multicenter Studies as Topic / Nerve Fibers, Myelinated - pathology / Nerve Fibers, Myelinated - physiology / Original / Physiological aspects / Research design / Risk factors / Sural Nerve - pathology / Sural Nerve - physiopathology / Triglycerides / Triglycerides - blood / Vibration