Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

Abstract

■ AbstractDiabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials.

Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints

“…It is common for clinicians to mask or relieve pain of human subjects with painful diabetic neuropathy by prescribing two or more medications (Javed et al, 2015; Vinik et al, 2013). Also, other complicated human diseases with multiple etiologies such as hypertension are also commonly treated with two or more medications (James et al, 2014).…”

Neuropathic pain: current definition and review of drug treatment

“…However, there is increased mortality with intensive insulin regimens in patients with established diabetic neuropathy compared to patients without neuropathy. 7 HIV-associated neuropathy presents an even more complex picture -starting antiretrovirals may initially improve symptoms although nerve damage may progress. Some antiretrovirals can cause neuropathy, and neurotoxicity may be a feature of concomitant medicines such as isoniazid for tuberculosis.…”

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“…As it is discussed a number of different therapeutic approaches that target the various pathogenetic mechanisms of diabetic neuropathy have been the subject of clinical trials [44].…”