Diabetic neuropathies

Abstract

Neuropathy is the most common "life-spoiling" complication of diabetes mellitus and the major cause of morbidity. While the primary long-term objective will be to find a cure for diabetes, in the immediate future the major goal is to prevent and reverse the chronic complications of the disease. The heterogeneity of diabetic neuropathy has for years escaped the attention of clinicians and investigators. Attempts have been made to distinguish the different clinical syndromes and the nerve fibre types affected without an in depth understanding of differences in pathogenesis.An improved classification of diabetic neuropathies is required which recognizes more fully the heterogeneity of this disease, as well as the possibility that the pathogenesis and profile of neuropathies encountered in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients may be distinct. Recent human and experimental studies provide an increased understanding of the diversity of underlying pathophysiological and biochemical abnormalities in the IDDM and NIDDM disorders, and how these may relate to the diverse phenotypic expression of diabetic neuropathies. The recommended classification forges closer links between pathology, neurobiology, and immunology and aims to provide a firmer foundation for investigations into the aetiology and rational treatment of diabetic neuropathies. Animal and human data now show or strongly indicate, using end-points specific for participating neuropathies, that diabetic neuropathies may be amenable to immunotherapy and neurotrophic factor treatment. This group was convened to examine the current state of knowledge of the pathogenesis and limited success of past treatments. After considerations of the heterogeneity of neuropathies and their aetiopathogenesis, they have arrived at the following recommendations. Classification of diabetic neuropathiesA wide variety of disturbances of peripheral nerve function are encountered in patients with diabetes. These can be broadly classified into: 1) rapidly reversible neuropathy; 2) persistent neuropathies; 3) focal/multifocal neuropathies. Rapidly reversible: Hyperglycaemic neuropathyPersistent symmetric polyneuropathies: a) distal somatic sensory/motor polyneuropathies (DSPN) involving predominantly large fibres; b) autonomic neuropathies (APN); c) small fibre neuropathies.Focal/multifocal neuropathies: a) cranial neuropathies; b) thoracoabdominal radiculopathies; c) focal limb neuropathies; d) proximal neuropathies; e) compression and entrapment neuropathies.

New insights into the metabolic and molecular basis for diabetic neuropathy

“…Progressive axonal degeneration, coupled with impaired regenerative capacity, in the type 1 diabetic BB/Wor rat result in a progressive nerve fiber loss, which is significantly milder in its type 2 counterpart, the BB/Z rat [24]. In human DPN, the spectrum of somatic DPN can be divided into reversible and persistent syndromes [6,9]. The latter are classified into sensory and motor syndromes of increasing severity, which reflect the natural history of DPN.…”

“…Diabetic neuropathies include several distinct syndromes, of which symmetric sensory polyneuropathy commonly associated with diabetic autonomic polyneuropathy are referred to as diabetic polyneuropathy (DPN). The various syndromes affecting the peripheral nervous system are separated into acute rapidly reversible syndromes and chronic progressive manifestations [6,9]. The mechanisms underlying DPN are multiple and appear to involve genetic predispositions and several interrelated metabolic and molecular abnormalities consequent to hyperglycemia and insulin and C-peptide deficiencies [1, 10 -14].…”

Management of painful diabetic neuropathy: What is new or in the pipeline for 2007?

“…The term "hyperglycemic neuropathy" has been used to describe sensory symptoms in patients whose diabetes is poorly controlled but that is rapidly reversible following institution of near-normoglycemia [2]. The most frequent form is DSP commonly associated with autonomic involvement.…”

“…However, due to the variety of the clinical syndromes with possible overlaps there is no universally accepted classification. The most widely used classification differentiates between rapidly reversible, persistent symmetric polyneuropathies, and focal or multifocal neuropathies [2].…”

Therapeutic Effects of Fenofibrate on Diabetic Peripheral Neuropathy by Improving Endothelial and Neural Survival in db/db Mice

“…Diabetic peripheral neuropathy (DPN) affects at least 50% of patients with diabetes, and is the leading cause of foot amputation [1], [2]. Hyperglycemia is likely the primary factor [3], which is associated with changes in endoneural metabolism, including increases in the polyol pathway, advanced glycation and protein kinase C, impairment of essential fatty acid metabolism, defective neurotropic factors, and reduced nerve blood supply [4], .…”