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

Diabetic polyneuropathy (DPN) continues to be generally considered as a "microvascular" complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, might be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron-specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of messenger ribonucleic acid (RNA) changes related to declines in structural proteins, increases in heat shock protein, increases in the receptor for advanced glycation end-products, declines in growth factor signaling and other changes. Insulin is recognized as a potent neurotrophic factor, and insulin ligation enhances neurite outgrowth through activation of the phosphoinositide 3-kinase-protein kinase B pathway within sensory neurons and attenuates phenotypic features of experimental DPN. Several interventions, including glucagon-like peptide-1 agonism, and phosphatase and tensin homolog inhibition to activate growth signals in sensory neurons, or heat shock protein overexpression, prevent or reverse neuropathic abnormalities in experimental DPN. Diabetic sensory neurons show a unique pattern of microRNA alterations, a key element of messenger RNA silencing. For example, let-7i is widely expressed in sensory neurons, supports their growth and is depleted in experimental DPN; its replenishment improves features of DPN models. Finally, impairment of pre-messenger RNA splicing in diabetic sensory neurons including abnormal nuclear RNA metabolism and structure with loss of survival motor neuron protein, a neuron survival molecule, and overexpression of CWC22, a splicing factor, offer further novel insights. The present review addresses these new aspects of DPN sensory neurodegeneration.
J Diabetes Investig 2018 Nov
PMID:Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. 2953 35

Diabetic polyneuropathy (DPN) is a complex and multifactorial entity in which various factors besides hyperglycemia play an important role. Symptoms of DPN are sensory, motor or autonomic. Intensive research proved that oxidative stress is the common denominator for the four major destructive pathways of hyperglycemia including increased hexosamine pathway flux, activation of Protein kinase-C (PKC) pathway, increased Advanced Glycated End-products (AGEs) formation, and increased Polyol Pathway flux. National data in Egypt confirms that more than 60% of Egyptian diabetic patients suffer from neuropathy. The most common complications of DPN are Cardiac Autonomic Neuropathy (CAN), diabetic foot and ulcers, neuromuscular disability, and anxiety. In addition, DPN affects the Quality of Life (QoL). According to common clinical practice, the common diagnostic tools are bed-side diagnosis and electrophysiological tests. Early diagnosis is critical to improve the prognosis of DPN and therapeutic intervention in the early phase. In this review, we provide a clear understanding of the pathogenesis, early diagnosis and the good management of DPN. Since the pathogenesis of DPN is multifactorial, its management is based on combination therapy of symptomatic; either pharmacological or non-pharmacological treatments, and pathogenic treatment. Alpha Lipoic Acid (ALA) is a potent anti-oxidant that has several advantages as a pathogenic treatment of DPN. So, in clinical practice, ALA may be prescribed for patients with early neuropathic deficits and symptoms. Patient education has an important role in the managemement of DPN.
Curr Diabetes Rev 2019
PMID:Review of Diabetic Polyneuropathy: Pathogenesis, Diagnosis and Management According to the Consensus of Egyptian Experts. 3081 79

Diabetic polyneuropathy, which is a chronic symmetrical length-dependent sensorimotor polyneuropathy, is the most common form of diabetic neuropathy. Although diabetic polyneuropathy is the most important risk factor in cases of diabetic foot, given its poor prognosis, the criteria for diagnosis and staging of diabetic polyneuropathy has not been established; consequently, no disease-modifying treatment is available. Most criteria and scoring systems that were previously proposed consist of clinical signs, symptoms and quantitative examinations, including sensory function tests and nerve conduction study. However, in diabetic polyneuropathy, clinical symptoms, including numbness, pain and allodynia, show no significant correlation with the development of pathophysiological changes in the peripheral nervous system. Therefore, these proposed criteria and scoring systems have failed to become a universal clinical end-point for large-scale clinical trials evaluating the prognosis in diabetes patients. We should use quantitative examinations of which validity has been proven. Nerve conduction study, for example, has been proven effective to evaluate dysfunctions of large nerve fibers. Baba's classification, which uses a nerve conduction study, is one of the most promising diagnostic methods. Loss of small nerve fibers can be determined using corneal confocal microscopy and intra-epidermal nerve fiber density. However, no staging criteria have been proposed using these quantitative evaluations for small fiber neuropathy. To establish a novel diagnostic and staging criteria of diabetic polyneuropathy, we propose three principles to be considered: (i) include only generalizable objective quantitative tests; (ii) exclude clinical symptoms and signs; and (iii) do not restrictively exclude other causes of polyneuropathy.
J Diabetes Investig 2020 Jan
PMID:Lumos for the long trail: Strategies for clinical diagnosis and severity staging for diabetic polyneuropathy and future directions. 3167 43

Chronic diabetic complications - both microvascular and macrovascular - have become serious health issues with their increasing prevalence paralleling the dramatic rise of the diabetic population worldwide. Of these complications, foot disease is a major cause of morbidity and mortality, consuming more health care resource than all other complications combined. Diabetic polyneuropathy and peripheral vascular disease constitute the two main risk factors, with trauma and foot infection being the most important initiating factors and contributors to delayed healing. Intracellular oxidative stress mediated by hyperglycaemia along with hypertension, dyslipidaemia and smoking constitute the main pathological processes in the aetiology of both macrovascular and microvascular disease. Whilst the former remains the major cause of overall mortality in diabetes, the role of microangiopathy in the pathogenesis of diabetes foot disease and its contribution to delayed wound healing in diabetes has yet to be fully understood and indeed continues to be debated. This article will review the key findings to date on structural and functional microvascular abnormalities in the diabetic foot skin and consider their contribution to impaired would healing.
Diabetes Metab Res Rev 2020 03
PMID:Microangiopathy: Is it relevant to wound healing in diabetic foot disease? 3184 61

Diabetic polyneuropathy is a common and disturbing complication of diabetes mellitus, presenting patients and caregivers with a substantial disease burden. Emerging mechanisms which are underlying diabetes may provide novel pathways to understand diabetic polyneuropathy (DPN). Specifically, non-coding RNA molecules consisting of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are implicated in the biological processes underlying DPN, and may link it to clinical spheres such as other metabolic and neural pathologies. Here, we elaborate on several candidate non-coding RNAs which may be associated with DPN via regulatory roles governing phenomena related to inflammatory, pain-provoking, and metabolic syndrome pathways. Specific examples include miRNAs such as miR-106a, -146a, -9, -29b, -466a, and -98; likewise, lncRNAs MIAT, PVT1, H19, MEG3, and MALAT1 are implicated, often co-affecting the involved pathways. Incorporating newly discovered regulators into what we know about specific clinical applications may highlight novel avenues for diagnosis, prevention, and intervention with DPN.
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PMID:Non-coding RNA regulators of diabetic polyneuropathy. 3245 50

Diabetic polyneuropathy (DPN) is a common complication of diabetes and is often associated with neuropathic pain. The mechanisms underlying development and maintenance of painful DPN are largely unknown, and quantification of intraepidermal nerve fiber density from skin biopsy, one of the neuropathological gold standard when diagnosing DPN, does not differentiate between patients with and without pain. Identification of possible pain pathophysiological biomarkers in patients with painful DPN may increase our knowledge of mechanisms behind neuropathic pain. Animal models of painful DPN have been shown to have an increased density of peptidergic nerve fibers (substance P and calcitonin gene-related peptide). In this study, we performed a detailed skin biopsy analysis in a well-characterized group of DPN patients with primarily small fiber involvement, with and without pain, and in healthy controls and test for correlation between skin biopsy findings and pain intensity and quantitative sensory testing. We found that although there was no difference in intraepidermal nerve fiber density using protein gene product 9.5 between patients with and without pain, patients with pain had increased density of dermal peptidergic fibers containing substance P and calcitonin gene-related peptide compared with patients with painless DPN and healthy controls. Peptidergic nerve fiber density correlated with pain ratings in patients with pain (R = 0.33; P = 0.019), but not with quantitative sensory testing results. In this article, we show, for the first time in humans, an increased density of dermal peptidergic fibers in painful DPN. These findings provide new insight in the pathophysiological mechanisms of pain in diabetes and open the research towards new therapeutic targets.
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PMID:Increased peptidergic fibers as a potential cutaneous marker of pain in diabetic small fiber neuropathy. 3283 93


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