Lipids and peripheral neuropathy

Abstract

Purpose of review Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy. Recent findings A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels. Summary Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.

Diabetic Wound-Healing Science

“…Other treatments for improving wound closure in patients with diabetes and neuropathy include antibiotics if an infection is present, as well as debridement and wound cleansing [ 25 ]. Recent evidence also suggests that hyperlipidemia, specifically hypertriglyceridemia, may play a role in the development of diabetic neuropathy and therefore, lipid-lowering drugs may prevent or even reverse the damage to nerve fibers in patients with diabetic neuropathy [ 26 ]. This approach to prevention is not often employed as therapies targeting neuropathy currently focus on reducing the pressure placed on the foot and relieving the need to itch [ 25 ].…”

The Efficacy of Fenofibrate in Addition to Atorvastatin in Patients of Type II Diabetes Mellitus

“…Interestingly, quite coinciding findings were revealed by Zhao et al, who concluded that following treatment with fenofibrate, there was a significant reduction in triglyceride levels and a marked increase in total HDL [ 16 ]. The Study for Atrial Fibrillation Reduction (SAFARI) trial also observed these findings, which saw a 23.6% reduction in triglyceride levels and an 8.8% increase in HDL following combined use of statin and fenofibrate [ 17 , 18 ].…”

Genomic DNA Methylation in Diabetic Chronic Complications in Patients With Type 2 Diabetes Mellitus

“…Most studies discovered that the prevalence of diabetic microvascular complications increased with age and duration ( 13 ). Hypertension and lipid metabolism disorders has a promoting effect on the development of microvascular lesion in diabetes ( 14 , 15 ). Another widely recognized factor is HbA1c, which can be used as an important indicator for blood glucose levels and diabetic microvascular complications ( 16 ).…”