Chapter I. Diabetic Peripheral Neuropathy

Vascular Impairment of Epineurial Arterioles of the Sciatic Nerve: Implications for Diabetic Peripheral Neuropathy

Mark A. Yorek^1,2,3

Abstract

This article reviews the impact of diabetes and its treatment on vascular function with a focus on the reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve. Another focus is the relationship between the dysregulation of neurovascular function and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. The etiology involves metabolic, vascular, and immunologic pathways besides neurohormonal growth factor deficiency and extracellular matrix remodeling. In the light of this complex etiology, an effective treatment for diabetic peripheral neuropathy has not yet been identified. Current opinion postulates that any effective treatment for diabetic peripheral neuropathy will require a combination of life style and therapeutic interventions. However, a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed before such a treatment strategy can be developed. After reading this review, the reader should have gained insight into the complex regulation of vascular function and blood flow to the sciatic nerve, and the impact of diabetes on numerous elements of vascular reactivity of epineurial arterioles of the sciatic nerve.

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Distal Sensorimotor Neuropathy: Improvements in Diagnosis

Prashanth R. J. Vas¹, Sanjeev Sharma², Gerry Rayman²

Abstract

Neurological complications of diabetes are common, affecting up to 50% of people with diabetes. In these patients, diabetic sensorimotor neuropathy (DSPN) is by far the most frequent complication. Detecting DSPN has traditionally been a clinical exercise that is based on signs and symptoms. However, the appearance of morphometric and neurophysiological techniques along with composite scoring systems and new screening tools has induced a paradigm change in the detection and stratification of DSPN and our understanding of its natural history and etiopathogenesis. These newer techniques have provided further evidence that changes in small nerve fiber structure and function precede large fiber changes in diabetes. Although useful, the challenge for the use of these new techniques will be their sensitivity and specificity when widely adopted and ultimately, their ability to demonstrate improvement when pathogenic mechanisms are corrected. Concurrently, we have also witnessed an emergence of simpler screening tools or methods that are mainly aimed at quicker detection of large fiber neuropathy in the outpatient setting. In this review, we have focused on techniques and tools that receive particular attention in the current literature, their use in research and potential use in the clinical environment.

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Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015

Nikolaos Papanas¹, Dan Ziegler^2,3

Abstract

Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities.

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Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

Saad Javed¹, Uazman Alam^1,2, Rayaz A. Malik^1,3

Abstract

Diabetic 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.

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