Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

Abstract

Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na + /K + -ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an © 2011 Bentham Science Publishers * Address correspondence to this author at the Room 420, School of Pharmacy Medical Sciences Campus-University of Puerto Rico, PO Box 365067, San Juan, Puerto Rico; Tel: (787) important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

“…These studies demonstrated that LA can accumulate in different parts of the cell, but only in small concentrations within mitochondria (117). LA has powerful antioxidant properties and is therefore suitable for the treatment of diseases related to oxidative stress; for example, short-term and long-term supplementation of LA (200-1800 mg/day) in type 2 diabetic patients have beneficial effects in maintenance of glycemic control (200). LA can exert beneficial effects by several mechanisms, including improvement in vascular endothelial cell function (257), decrease in inflammation (104), amelioration of lipid abnormalities (376), and protection against myocardial ischemia/reperfusion injury (341) or antihypertensive effects (83).…”

Management of peripheral neuropathy symptoms with a fixed dose combination of high-dose vitamin B1, B6 and B12: A 12-week prospective non-interventional study in Indonesia

“…1 Symptoms of PN can be diverse, patients often experience prickling, tingling, numbness, a reduced ability to feel pain or changes in temperature, a burning pain, and allodynia. [2][3][4][5] The common causes of PN include systemic diseases like diabetes, environmental toxins, vitamin and nutritional deficiency, drug-induced traumatic injury, excessive consumption or alcohol abuse, immune system diseases or viral infection, hypothyroidism, genetic and idiopathic. [5][6][7][8][9] Although the exact incidence of PN is not well documented, there is data showing a prevalence of 8.1% in general population at the age of 40-49.…”

Comparative Study of Vitamin B Complex Combined with Alpha Lipoic Acid versus Vitamin B Complex in Treatment of Diabetic Polyneuropathy in Type 2 Diabetic Patients

“…As glycemic variability leads to oxidative stress, antioxidants such as ALA are valuable therapeutic option for DPN [37]. ALA can potently regenerate other antioxidants such as vitamin C, vitamin E and glutathione through redox cycling [38]. In the present trial, the effect of oral supplementation with ALA, 600 mg daily dose, on DPN was evaluated when given with vitamin B complex compared with vitamin B complex alone.…”