Elevated Triglycerides Correlate with Progression of Diabetic Neuropathy

  1. Timothy D. Wiggin1,
  2. Kelli A. Sullivan1,
  3. Rodica Pop-Busui2,
  4. Antonino Amato4,
  5. Anders A. F. Sima3 and
  6. Eva L. Feldman (efeldman{at}
  1. 1University of Michigan Department of Neurology
  2. 2University of Michigan Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes
  3. 3Wayne State University Departments of Pathology and Neurology
  4. 4Sigma-Tau Research


    Objective: To evaluate mechanisms underlying diabetic neuropathy (DN) progression using indices 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, vibration perception thresholds, clinical symptom scores and a visual analogue scale for pain were analyzed in participants with DN. A loss of ≥ 500 fibers/mm2 in sural nerve MFD over 52 weeks was defined as progressing DN and a MFD loss of ≤ 100 fibers/mm2 during the same time interval as non-progressing DN. The progressing and non-progressing 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 non-progressing cohort remained unchanged. MFD was not affected by active drug treatment (p=0.87), diabetes duration (p=0.48), age (p=0.11) or body mass index (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/moderate DN, 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 DN.


      • Received December 19, 2008.
      • Accepted April 6, 2009.

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