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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic neuropathy represents a heterogeneous pathology taking place during diabetes mellitus (DM) evolution, hiding possibilities for rapid evolution which threaten even the life of the diabetic person. As a result, the recognition as precocious as possible of the neuropathy-induced alterations and the ways of treating this complication are essential. Diabetic neuropathy is classified in peripheral and vegetative, each of them with numerous clinical forms. Nevertheless, its etiopathogeny remains not totally understood, many theories existing for explaining it, its development being probably the result of a mixture of pathogenic mechanisms. Although there are difficulties in appreciation of the neuropathy prevalence in diabetic people, it is generally known that this alteration is one of the most frequent and invalidant major complication that affects this population, treatment as precocious as possible being essential. alpha-lipoic acid, substance with antioxidant properties, plays a central role in the energetic metabolism, principally functioning as a coenzyme in multienzymatic mitochondrial complexes alpha-lipoic acid has complex actions on different levels of the human organism, having many indications in different diseases, including DM. The results of numerous clinical studies have confirmed its efficacy in treating diabetic neuropathy. The present study has proposed itself to investigate the long-term effect of the short-term i.v. treatment with Thiogamma 600 (alpha-lipoic acid) in patients having type I or 2 DM, proving neuropathy symptoms and signs reduction evaluated in 3 months time, without metabolic control of the disease. If this amelioration proves to be persistent in time, with or without continuing the medication, this treatment will represent the most evident and efficient present solution in neuropathy.
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PMID:Diabetic neuropathy--choices of treatment. 1552 40

Diabetic neuropathy is a major complication of poorly controlled diabetes mellitus. Aldose reductase, the first enzyme of the polyol pathway, is thought to play a role in initiating the metabolic damage to peripheral nerves during hyperglycemia. Aldose reductase inhibitors (ARIs) have been proposed to dampen the flux of glucose through the pathway during hyperglycemia; however, clinical trials in diabetic patients to demonstrate efficacy in the prevention or amelioration of diabetic neuropathy have failed thus far. Recent improved understanding of the pitfalls of past trials and some improved ARIs and clinical evaluation instruments show promise that success in the 20-plus year search for efficacious ARIs may soon be at hand.
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PMID:Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004? 1553 2

The incidence of diabetes and its complication have rapidly increased. Decreased quality of life and increased mortality are the major problems of people with diabetes. These problems are mainly caused by chronic complications. The incidence of diabetic neuropathy, which is one of these chronic complications, approaches 50% in most diabetic patients. The intensive metabolic management alone cannot completely prevent the development and progression of diabetic complications. Therefore, blocking and management of pathogenic mechanism of complication are required. Pathogenesis of diabetic neuropathy has multifactorial causes. Diabetic neuropathy is thought to occur both from direct hyperglycemia-induced damage to the nerve parenchyma and from neuronal ischemia brought about indirectly by hyperglycemia-induced decreases in neurovascular flow. The effects of hyperglycemia get converted to neuronal dysfunction via at least three secondary biochemical pathways: the polyol pathway, non-enzymatic glycation of proteins, oxidative stress and protein kinase C, and the interactions between them. Because of these interactions, interference with one of these biochemical pathways could either worsen or attenuate the effects of the others. So, the use of therapeutic intervention of these pathways is inevitable and valid to prevent the progression of diabetic neuropathy. As yet, a satisfactory and fundamental, preventive, and therapeutic method is not available with us to prevent progression. So, we will introduce the earlier diagnostic methods of diabetic neuropathy and will discuss the advantages and limitations of each method.
Diabetes Res Clin Pract 2004 Dec
PMID:Can diabetic neuropathy be prevented? 1556 81

Diabetic neuropathy occurs in a stocking and glove distribution consistent with a systemic metabolic disease. Historically, this concept led to the conclusion that the only role for surgery in a patient with diabetic neuropathy is for treatment of wounds, amputation, or reconstruction of a Charcot foot. This article reviews the basic scientific and clinical research that support the concepts that metabolic neuropathy renders the peripheral nerve susceptible to compression in patients with diabetes and that decompression of lower extremity peripheral nerves in these patients can relieve pain, restore sensation, and prevent ulceration and amputation.
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PMID:Diabetic neuropathy: review of a surgical approach to restore sensation, relieve pain, and prevent ulceration and amputation. 1556 8

Diabetic neuropathy (DN) is a complication of diabetes that affects the distal terminals of lengthy-projecting sensory axons. To determine whether diabetes-induced axonal degeneration induces gene expression similar to nerve injury, the expression of activating transcription factor 3 (ATF3) by primary sensory neurons was examined in an experimental mouse model of DN. Diabetes was induced using streptozotocin in C57BL/6 mice, and ATF3 expression in lumbar dorsal root ganglia was assessed at different time points and correlated with the markers of unmyelinated and myelinated neuronal populations. ATF expression was first evident 3 weeks after diabetes induction in both small unmyelinated and large myelinated neurons, but it was more prevalent in larger neurons. At 6 weeks, ATF3 was expressed by neurons among smaller size ranges, but this shift occurred principally within myelinated populations. The retrograde labeling of neurons innervating the flank and paw skin using Fluoro-Gold labeled appropriate percentages of ATF3-positive neurons at 3 weeks, suggesting ATF3 is expressed by neurons capable of transporting substances. However, the percentage of double-labeled neurons was substantially reduced at 6 weeks, suggesting this capacity decreases during disease progression. Finally, behavioral responses to noxious cutaneous stimuli were assessed. Although no differences to radiant heat were observed, diabetic mice developed severe mechanical hypoalgesia 4-5 weeks after diabetes induction. These results demonstrate that the diabetes-induced damage of sensory axons can induce the expression of genes linked to peripheral nerve injury and may identify neurons undergoing nerve damage. Finally, the ability to detect sensory deficits in diabetic mice occurs after the expression of injury-related gene ATF3, suggesting that nerve damage may be underway prior to the appearance of behavioral deficits.
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PMID:Diabetes-induced expression of activating transcription factor 3 in mouse primary sensory neurons. 1557 37

Diastolic orthostatic hypotension measured 1 min after standing up (OH-D1), and systolic OH measured 3 min after standing up (OH-S3) increase vascular mortality risk among older adults. We hypothesized that the risk is especially high among diabetic patients. The orthostatic test was carried out in a standard way by a trained nurse in 868 subjects (79% of a representative population sample) and 98 of them were diabetic treated with oral hypoglycemic agents or insulin. OH-D1 occurred in 9 (9%) diabetic patients and in 43 (6%) other subjects of the cohort (Chi-Square; P = 0.157), and OH-S3, correspondingly, in 28 (29%) and 140 (18%) (P = 0.014). Absent patellar vibration sense, absent patellar reflex and resting heart rate was higher, and cardioacceleration early after active standing up was lower in the diabetic patients. According to Cox Proportional Hazards modelling, after adjustment for other baseline variables (age, sex, history of myocardial infarction, current smoking, chest pain and systolic blood pressure), the hazard ratio of vascular death as regards OH-D1 was 3.69 (95% confidence intervals 1.54-8.84), and that as regards OH-S3 was 2.70 (1.16-6.29). Among the persons free of diabetes treated with oral hypoglycaemic agents or insulin (N = 770), survival for vascular death did not differ in regard to presence and absence of OH-D1 and OH-S3. Our results suggest that diabetes patients with orthostatic hypotension carry a high risk of vascular death. Diabetic neuropathy is a plausible explanation to our findings.
Diabetes Res Clin Pract 2005 Feb
PMID:Orthostatic hypotension predicts vascular death in older diabetic patients. 1564 76

Diabetic neuropathy is a common complication of diabetes mellitus. Effective blood glucose control retards changes in nerve conduction velocity in type 1 diabetes. This study examined the relationship between glycemic control and electrophysiologic changes in diabetic neuropathy in 57 type 2 diabetic patients. Nerve conduction in the peroneal motor nerve, tibial motor nerve, and sural nerve were measured at study entry and at follow-up 24+/-3.12 months later. Changes in individual nerves are expressed as a percentage change (PC) and overall electrophysiologic changes are expressed as the sum of individual PCs. The PCs for peroneal motor nerve velocity, tibial motor nerve velocity, and sural nerve velocity were all lower in patients with a mean HbA1c of 8.5% or less compared with those in patients with a mean HbA1c of more than 8.5%, and SPCV (sum of PC in velocity) was significantly inversely correlated with mean HbA1c. However, there was no significant difference in SPCV in subjects with or without hypertension, hypertriglyceridemia, or low high-density lipoprotein cholesterol concentration. In conclusion, hyperglycemia is the most important etiology for electrophysiologic progression in type 2 diabetic patients. Furthermore, a mean HbA1c of more than 8.5% will result in significant deterioration in electrophysiology.
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PMID:Effect of glycemic control on electrophysiologic changes of diabetic neuropathy in type 2 diabetic patients. 1575 84

Diabetic neuropathy is based on the impairment of nerve blood flow and the metabolic disorder. Although the vasodilating agents and anticoagulants improve nerve function and symptoms in diabetic neuropathy, more effective treatments are needed. Because endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood, many studies have shown that transplantation of EPCs improves circulation to ischemic tissues. In this study, we have demonstrated that therapeutic neovascularization using human umbilical cord blood-derived EPCs reversed diabetic neuropathy. EPCs were isolated and expanded on day 7 of culture from cord blood mononuclear cells. Unilateral intramuscular injection of EPCs into hindlimb skeletal muscles significantly ameliorated impaired sciatic motor nerve conduction velocity and sciatic nerve blood flow in the EPC-injected side of streptozotocin-induced diabetic nude rats compared with the saline-injected side of diabetic nude rats. Histological study revealed an increased number of microvessels in hindlimb skeletal muscles in the EPC-injected side of diabetic rats. These findings suggest that transplantation of EPCs from cord blood may be a useful treatment for diabetic neuropathy.
Diabetes 2005 Jun
PMID:Therapeutic neovascularization using cord blood-derived endothelial progenitor cells for diabetic neuropathy. 1591 5

Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent of patients with diabetes. It is a late finding in type 1 diabetes but can be an early finding in type 2 diabetes. The primary types of diabetic neuropathy are sensorimotor and autonomic. Patients may present with only one type of diabetic neuropathy or may develop combinations of neuropathies (e.g., distal symmetric polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual dysfunction. Strict glycemic control and good daily foot care are key to preventing complications of diabetic neuropathy.
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PMID:Evaluation and prevention of diabetic neuropathy. 1595 41

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. A growing body of evidence suggests that oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defense is implicated in the pathogenesis of diabetic neuropathy. Markers of oxidative stress such as superoxide anion and peroxynitrite production are increased in diabetic patients in relation to the severity of polyneuropathy. In experimental diabetic neuropathy, oxygen free-radical activity in the sciatic nerve is increased, and treatment with thioctic acid, a potent lipophilic antioxidant, results in prevention or improvement of the diabetes-induced neurovascular and metabolic abnormalities in various organ systems. Pharmacodynamic studies have shown that thioctic acid favorably influences the vascular abnormalities of diabetic polyneuropathy such as impaired microcirculation, increased indices of oxidative stress, and increased levels of markers for vascular dysfunction, such as thrombomodulin, albuminuria, and nuclear factor-kappaB. Thus far, seven controlled randomized clinical trials of thioctic acid in patients with diabetic neuropathy have been completed (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN I-III], Deutsche Kardiale Autonome Neuropathie [DEKAN], Oral Pilot [ORPIL], Symptomatic Diabetic Neuropathy [SYDNEY], Neurological Assessment of Thioctic Acid in Neuropathy [NATHAN] II) using different study designs, durations of treatment, doses, sample sizes, and patient populations. Recently, a comprehensive analysis was undertaken of trials with comparable designs that met specific eligibility criteria for a meta-analysis to obtain a more precise estimate of the efficacy and safety of thioctic acid (600mg intravenously for 3 weeks) in diabetic patients with symptomatic polyneuropathy. This meta-analysis included the largest sample of diabetic patients (n = 1258) ever to have been treated with a single drug or class of drugs to reduce neuropathic symptoms, and confirmed the favorable effects of thioctic acid based on the highest level of evidence (Class Ia: evidence from meta-analyses of randomized, controlled trials). The following conclusions can be drawn from these trials: (i) short-term treatment for 3 weeks using intravenous thioctic acid 600 mg/day reduces the chief symptoms of diabetic polyneuropathy to a clinically meaningful degree; (ii) this effect on neuropathic symptoms is accompanied by an improvement of neuropathic deficits, suggesting potential for the drug to favorably influence underlying neuropathy; (iii) oral treatment for 4-7 months tends to reduce neuropathic deficits and improve cardiac autonomic neuropathy; and (iv) clinical and postmarketing surveillance studies have revealed a highly favorable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with thioctic acid (NATHAN I) is being conducted in North America and Europe to investigate effects on progression of diabetic polyneuropathy, using a clinically meaningful and reliable primary outcome measure that combines clinical and neurophysiological assessment.
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PMID:Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. 1602 13


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