Abstract 18987: Fenofibrate Reduces Peripheral Neuropathy in Type 2 Diabetes: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study
Introduction: Peripheral neuropathy, a microvascular complication of diabetes, is a major contributor to lower limb ulcer formation and amputation and their devastating consequences. The aim of this analysis was to explore characteristics associated with neuropathy and the effect of the lipid-modifying drug, fenofibrate, on neuropathy.
Methods: 9795 patients with type 2 diabetes mellitus were randomised to receive fenofibrate 200 mg/day or matching placebo for 5 years. The presence of neuropathy symptoms was recorded at baseline and sensation tested by a standard monofilament technique, repeated at 2 years and study close. All nontraumatic lower limb amputations were recorded, and classified as major or minor. Risk models used exhaustive search methods in logistic regression.
Results: 5.8% of participants (564 of 9795) had documented monofilament neuropathy at baseline. Strong associations with neuropathy included female sex, history of prior CVD, diabetes duration (per 10 years), insulin use and height, all increasing risk by around 50% or more (all P<0.01). Additional factors associated with onset of new neuropathy include prior retinopathy, age, high HbA1C, and hypertriglyceridemia (all P<0.03). By study close, neuropathy had increased to 8.0% of placebo patients, compared with 6.6% of those receiving fenofibrate (between-group difference, adjusted for baseline incidence of neuropathy, P=0.003).This reflected an 18% reduction in new neuropathy (OR 0.82, 95% CI 0.67-1.01, P=0.06) and a significantly greater reversal of baseline neuropathy with treatment (OR 1.67, 95% CI 1.14-2.38, P=0.009). Neuropathy was one of the strongest predictors of amputation, increasing the risk of a first amputation approximately threefold (HR 2.7, 95% CI 1.8-4.1; P<0.001) and of a minor amputation even more.
Conclusions: Long-term use of fenofibrate reduced overall neuropathy and increased the reversal of pre-existing neuropathy in type 2 diabetes, although the mechanisms remain unknown. These benefits are likely to partly explain the large 37% reduction seen in the risk of total amputations with fenofibrate in the FIELD study.
- © 2010 by American Heart Association, Inc.