Classification, Differential Diagnosis, and Staging of Diabetic Peripheral Neuropathy
ABSTRACT The peripheral nerve disorders associated with diabetes are complex and probably involve a variety of causative mechanisms. This may give rise to difficulty in the classification of individual cases. A broad separation into rapidly reversible or more persistent phenomena is helpful. The former, which can be categorized as "hyperglycemic neuropathy," include minor sensory symptoms, reduced nerve conduction velocity, and resistance to ischemic conduction failure. From analogy with experimental studies in animals, nerve hypoxia is likely to play a significant role in their origin. Of the more persistent phenomena, a distal symmetric polyneuropathy that predominantly affects sensory and autonomic function is the most common manifestation. A distal axonopathy of dying-back type may represent the underlying pathogenetic basis. Other more persistent phenomena consist of focal and multifocal lesions giving rise to cranial, thoraco-abdominal, and limb neuropathies, including proximal lower limb motor neuropathy (diabetic amyotrophy). Some of these may have an ischemic basis. Multifocal proximal lesions can summate to produce an approximately symmetric diffuse distal neuropathy. Focal lesions at sites of entrapment or external compression may reflect an abnormal susceptibility of diabetic nerve to compressive damage. There is also evidence that focal inflammatory, including vasculitic, lesions may be involved in proximal lower limb neuropathies. Finally, superimposed chronic inflammatory demyelinating polyneuropathy may occur. For the evaluation of possible treatment regimens, it is essential that cases should be correctly classified as to type. Thus, the features falling into the category of hyperglycemic neuropathy should not contaminate the assessment of distal symmetric polyneuropathy. For this type, a widely accepted scheme for staging devised by P. J. Dyck is available. Other schemes are also available for the assessment of such cases, with differing degrees of complexity. Evaluation by serial nerve biopsies has also been proposed.
- SourceAvailable from: Shahrad Taheri
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- "The diabetic neuropathies represent a heterogeneous group of neuropathies affecting different parts of the nervous system, including generalized symmetric polyneuropathies, focal and multifocal neuropathies, and autonomic neuropathy . "
ABSTRACT: An increasing body of evidence suggests that obstructive sleep apnoea (OSA) is independently associated with an increased risk of cardiovascular disease, glucose intolerance, and deteriorations in glycaemic control. Despite the knowledge of a multifactorial pathogenesis of long-term diabetes complications, there is a paucity of information on impact of comorbidities associated with chronic intermittent hypoxemia on development and progression of chronic diabetes complications. This review explores the clinical and scientific overlap of OSA and type 2 diabetes mellitus (T2DM) and its possible impact on the development and progression of diabetes macrovascular and microvascular complications. Multiple prospective observational cohort studies have demonstrated that OSA significantly increases the risk of cardiovascular disease independent of potential confounding risk factors. The current evidence further suggests that OSA with concurrent T2DM is associated with an increased risk of oxidative stress-induced damage of vulnerable endothelial and mesangial cells and peripheral nerves. Further studies are needed to validate the impact of OSA treatment on diabetes micro- and macrovascular complications. Since it is presently still unknown whether OSA treatment may provide a diabetes-modifying intervention that could delay or halt the progression of chronic diabetes complications, the emphasis is on early diagnosis and satisfactory treatment of both OSA and T2DM.Diabetes Research and Clinical Practice 05/2014; 104(2). DOI:10.1016/j.diabres.2014.01.007 · 2.54 Impact Factor
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- "However, the most common neuropathy resulting from diabetes is peripheral neuropathy, described as a distal symmetrical polyneuropathy (Thomas, 1997). In diabetic patients, indices of peripheral neuropathy range from hyperalgesia and allodynia to progressive hypoalgesia and loss of sensation while the most widely studied functional disorder is nerve conduction velocity slowing (Greene et al., 1999). "
ABSTRACT: There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy, and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the peripheral nervous system (PNS). In this study, we compared indexes of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and amyloid precursor protein (APP) overexpressing transgenic mice. Insulin-deficient and APP transgenic mice displayed similar patterns of peripheral neuropathy with decreased motor nerve conduction velocity, thermal hypoalgesia, and loss of tactile sensitivity. Phosphorylation of the insulin receptor and glycogen synthase kinase 3β (GSK3β) was similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels, and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.Neuroscience 12/2011; 202:405-12. DOI:10.1016/j.neuroscience.2011.11.032 · 3.33 Impact Factor
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- "fiber loss, which is significantly milder in its type 2 counterpart, the BBZDR/Wor rat (Sima et al., 2000). In human DPN, the spectrum of somatic DPN can be divided into reversible and persistent syndromes (Sima et al., 1997b; Thomas, 1997). The latter is classified into sensory and motor syndromes of increasing severity, which reflect the natural history of DPN. "
ABSTRACT: The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucose-independent effects. Preclinical studies have demonstrated dose-dependent effects on Na+,K(+)-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.Experimental Diabesity Research 01/2004; 5(1):65-77. DOI:10.1080/15438600490424541