OBJECTIVETo evaluate mechanisms underlying diabetic neuropathy progression using indexes of sural nerve morphometry obtained from two identical randomized, placebo-controlled clinical trials.RESEARCH DESIGN AND METHODSSural 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/mm2 in sural nerve MFD over 52 weeks was defined as progressing diabetic neuropathy, and a MFD loss of ≤100 fibers/mm2 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.RESULTSAt 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).CONCLUSIONSIn 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.

Among these ambulatory ESRD patients, peak VO2 was a stronger predictor of survival than many traditional prognostic variables, some of which are subject to ceiling effects. Exercise capacity may thus provide incremental prognostic information concerning healthier ESRD patients. Because peak VO2 may be modified by exercise training, the potential of exercise as an intervention to improve survival is suggested.

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