WorldWideScience

Sample records for human diabetic neuropathy

  1. [Diabetic neuropathy].

    Science.gov (United States)

    Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.

  2. [Diabetic neuropathy].

    Science.gov (United States)

    Chudzik, Wiesław; Kaczorowska, Beata; Przybyła, Monika; Chudzik, Bartosz; Gałka, Małgorzata

    2007-01-01

    Diabetic neuropathy is most common chronic complication of diabetes mellitus. It is responsible for substantial morbidity, increased mortality and impaired quality of life. Patogenesis of diabetic neuropathy is complex. Chronic hyperglycemia is a major factor induces nerve fibers injury. High level of glucose stimulate the polyol pathway causing osmotic stress and enhance reactive oxygen species generation, as well as it play an important role in diabetic angiopathy development. Distal symmetric polineuropathy is most common type of diabetic neuropathy. Many patient may develop combinations of neuropathies concerning somatic and autonomic system. Early diagnosis and administered suitable treatment are necessary to reduce severe complication of diabetic neuropathy as well as strict glycemic control and risk factor increased.

  3. Diabetic Neuropathies.

    Science.gov (United States)

    Izenberg, Aaron; Perkins, Bruce A; Bril, Vera

    2015-08-01

    Diabetes mellitus is a common condition and diabetics are prone to develop a spectrum of neuropathic complications ranging from symmetric and diffuse to asymmetric and focal neuropathies that may be associated with significant morbidity. Diabetic sensorimotor polyneuropathy is the most common of these complications, occurring in patients with type 1 and 2 diabetes mellitus, as well as in those with prediabetes and glucose intolerance. In this review, the authors discuss the wide variety of neuropathies that can present in the context of diabetes, including the clinical manifestations, diagnostic features, and approach to management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Management of Diabetic Neuropathy

    OpenAIRE

    Ali, Raymond Azman

    2003-01-01

    Diabetes mellitus is the commonest cause of neuropathy worldwide. Diabetic neuropathy (DN) develops in about 4–10% of diabetic patients after 5 years and in 15% after 20 years. Four main mechanisms have been postulated to underlie the pathogenesis of DN. Diabetic neuropathy can be divided into symmetrical and asymmetrical neuropathies. Diabetic Autonomic Neuropathy (DAN) parallels the severity of DSN, and affects primarily the cardiovascular, gastrointestinal, genitourinary and integumentary ...

  5. Diabetic autonomic neuropathy.

    Science.gov (United States)

    Freeman, Roy

    2014-01-01

    Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.

  6. Diabetic neuropathies: diagnosis and management.

    Science.gov (United States)

    Deli, Gabriella; Bosnyak, Edit; Pusch, Gabriella; Komoly, Samuel; Feher, Gergely

    2013-01-01

    Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective. © 2013 S. Karger AG, Basel.

  7. Diabetic radiculoplexus neuropathies.

    Science.gov (United States)

    Laughlin, Ruple S; Dyck, P James B

    2014-01-01

    Diabetic radiculoplexus neuropathies (DRPN) are neuropathies clinically and pathologically distinct from the neuropathy typically associated with diabetes (DPN). DRPN are usually subacute in onset, painful, and often demonstrate a monophasic course with incomplete recovery. Pathologically, these neuropathies are due to ischemic injury from altered immunity and often have features suggestive or diagnostic of microvasculitis. Unlike DPN, immune therapy may be helpful in treatment of these conditions given their pathological substrate and therefore are important to identify early and distinguish from other neuropathies that occur in patient with diabetes.

  8. Diabetic neuropathy in children.

    Science.gov (United States)

    Mah, Jean K; Pacaud, Danièle

    2014-01-01

    The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.

  9. Nerve Damage (Diabetic Neuropathies)

    Science.gov (United States)

    ... normally. A woman may have difficulty with arousal, lubrication, or orgasm. Sweat Glands Autonomic neuropathy can affect ... performed in people with diabetes. Comprehensive foot care programs can reduce amputation rates by 45 to 85 ...

  10. Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy.

    OpenAIRE

    Sima, A A; Nathaniel, V; Bril, V; McEwen, T A; Greene, D A

    1988-01-01

    Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating ins...

  11. Diabetic Neuropathy: Mechanisms to Management

    OpenAIRE

    2008-01-01

    Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to al...

  12. Catecholamines and diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1995-01-01

    In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors...

  13. Peripheral Neuropathy in Mouse Models of Diabetes.

    Science.gov (United States)

    Jolivalt, Corinne G; Frizzi, Katie E; Guernsey, Lucie; Marquez, Alex; Ochoa, Joseline; Rodriguez, Maria; Calcutt, Nigel A

    2016-09-01

    Peripheral neuropathy is a frequent complication of chronic diabetes that most commonly presents as a distal degenerative polyneuropathy with sensory loss. Around 20% to 30% of such patients may also experience neuropathic pain. The underlying pathogenic mechanisms are uncertain, and therapeutic options are limited. Rodent models of diabetes have been used for more than 40 years to study neuropathy and evaluate potential therapies. For much of this period, streptozotocin-diabetic rats were the model of choice. The emergence of new technologies that allow relatively cheap and routine manipulations of the mouse genome has prompted increased use of mouse models of diabetes to study neuropathy. In this article, we describe the commonly used mouse models of type 1 and type 2 diabetes, and provide protocols to phenotype the structural, functional, and behavioral indices of peripheral neuropathy, with a particular emphasis on assays pertinent to the human condition. © 2016 by John Wiley & Sons, Inc.

  14. [Atypical neuropathies associated with diabetes].

    Science.gov (United States)

    Lozeron, P

    2014-12-01

    Diabetes is the leading cause of neuropathy worldwide and, due to the epidemic progression of the affection, prevalence of diabetic neuropathies will increase in the near future. Beside the typical diabetic neuropathy pattern and the common entrapment neuropathies, several unusual clinical forms have been described with either a symmetrical or an asymmetrical pattern. Treatment-induced neuropathy is an acute sensory affection most commonly related to acute glycemic control. Pain is debilitating and associated with vegetative dysfunction. Prevention is important, as resolution is often incomplete. Several patterns or asymmetrical neuropathies of inflammatory and ischemic origin were described long ago in the lower limb. They are debilitating, most often painful and require steroid treatment. Other patterns affecting the thoracolumbar region or the upper limbs or involving a painless motor deficit must be identified as specific treatments are sometimes needed. An association between diabetes and chronic inflammatory demyelinating polyneuropathy has not been demonstrated but diagnosis may be suggested due to the misleading low conduction velocities seen in classical diabetic neuropathy. Like any other patient, the diabetic patient may present a neuropathy unrelated to diabetes. To facilitate patient care, neurologists should be aware of such clinical entities. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. The Spectrum of Diabetic Neuropathies

    Science.gov (United States)

    Tracy, Jennifer A.; Dyck, P. James B.

    2009-01-01

    Diabetes mellitus is associated with many different neuropathic syndromes, ranging from a mild sensory disturbance as can be seen in a diabetic sensorimotor polyneuropathy, to the debilitating pain and weakness of a diabetic lumbosacral radiculoplexus neuropathy. The etiology of these syndromes has been extensively studied, and may vary among metabolic, compressive, and immunological bases for the different disorders, as well as mechanisms yet to be discovered. Many of these disorders of nerve appear to be separate conditions with different underlying mechanisms, and some are directly caused by diabetes mellitus, whereas others are associated with it but not caused by hyperglycemia. We discuss a number of the more common disorders of nerve found with diabetes mellitus. We discuss the symmetrical neuropathies, particularly generalized diabetic polyneuropathy, and then the focal or asymmetrical types of diabetes-associated neuropathy. PMID:18194747

  16. Entrapment neuropathies in diabetes mellitus

    Science.gov (United States)

    Rota, Eugenia; Morelli, Nicola

    2016-01-01

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features. PMID:27660694

  17. Entrapment neuropathies in diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Eugenia; Rota[1; Nicola; Morelli[1

    2016-01-01

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms,are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM,particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.

  18. The Spectrum of Diabetic Neuropathies

    OpenAIRE

    Tracy, Jennifer A.; Dyck, P. James B.

    2008-01-01

    Diabetes mellitus is associated with many different neuropathic syndromes, ranging from a mild sensory disturbance as can be seen in a diabetic sensorimotor polyneuropathy, to the debilitating pain and weakness of a diabetic lumbosacral radiculoplexus neuropathy. The etiology of these syndromes has been extensively studied, and may vary among metabolic, compressive, and immunological bases for the different disorders, as well as mechanisms yet to be discovered. Many of these disorders of nerv...

  19. Pathogenesis of Painful Diabetic Neuropathy

    OpenAIRE

    Amir Aslam; Jaipaul Singh; Satyan Rajbhandari

    2014-01-01

    The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN) is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person's daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin o...

  20. Evaluation and Prevention of Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Pajouhi M

    2007-07-01

    Full Text Available Background: Diabetic neuropathy is an incapacitating disease that afflicts almost 50 percent of patients with diabetes. A late finding in type 1 diabetes, diabetic neuropathy can be an early finding in non insulin-dependent diabetes. Diabetic neuropathies are divided primarily into two groups, sensorimotor and autonomic. Patients may acquire only one type of diabetic neuropathy or may present with combinations of neuropathies, such as autonomic neuropathy or distal symmetric polyneuropathy, the latter of which the most common form. Motor deficits, orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis, bladder dysfunction, and sexual dysfunction can also result from diabetic neuropathy. Strict control of blood sugar, combined with proper daily foot care, is essential to avoid the complications of this disorder. With the potential to afflict any part of the nervous system, diabetic neuropathy should be suspected in all patients with type 2 diabetes as well as patients who have had type 1 diabetes for over five years. Although some patients with diabetic neuropathy notice few symptoms, upon physical examination mild to moderately severe sensory loss may be noted by the physician. Idiopathic neuropathy has been known to precede the onset of type 2 diabetes.

  1. Cardiovascular autonomic neuropathy in diabetes

    DEFF Research Database (Denmark)

    Spallone, Vincenza; Ziegler, Dan; Freeman, Roy

    2011-01-01

    Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control i....... Evidence on the cost-effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be given for most therapeutic approaches to CAN. Copyright © 2011 John Wiley & Sons, Ltd....... in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidemia, obesity and glycaemic control...

  2. Inflammation: therapeutic targets for diabetic neuropathy.

    Science.gov (United States)

    Zhou, Jiyin; Zhou, Shiwen

    2014-02-01

    There are still no approved treatments for the prevention or of cure of diabetic neuropathy, and only symptomatic pain therapies of variable efficacy are available. Inflammation is a cardinal pathogenic mechanism of diabetic neuropathy. The relationships between inflammation and the development of diabetic neuropathy involve complex molecular networks and processes. Herein, we review the key inflammatory molecules (inflammatory cytokines, adhesion molecules, chemokines) and pathways (nuclear factor kappa B, JUN N-terminal kinase) implicated in the development and progression of diabetic neuropathy. Advances in the understanding of the roles of these key inflammatory molecules and pathways in diabetic neuropathy will facilitate the discovery of the potential of anti-inflammatory approaches for the inhibition of the development of neuropathy. Specifically, many anti-inflammatory drugs significantly inhibit the development of different aspects of diabetic neuropathy in animal models and clinical trials.

  3. New Generation Antidepressants in Painful Diabetic Neuropathy

    OpenAIRE

    Gutiérrez-Álvarez, Ángela-María; Carlos B. Moreno

    2011-01-01

    The incidence of diabetic neuropathy increases with the duration of diabetes and the degree of hyperglycaemia. Pain is one of the most common and incapacitating symptoms of diabetic neuropathy and its pharmacological control is complex. The effectiveness of antidepressive agents has been described in different types of neuropathic pain, but their effectiveness, when used as analgesics in painful diabetic neuropathy, still remains controversial. Objective: To review the possible role of new-ge...

  4. Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores

    NARCIS (Netherlands)

    Meijer, J.W.; Lefrandt, J.D.; Links, T.P.; Smit, J.A.; Stewart, R.E.; van der Hoeven, J.H.; Hoogenberg, K.

    2003-01-01

    OBJECTIVE - To evaluate the discriminative power of the Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores for diagnosing diabetic polyneuropathy (PNP), as well as their relation with cardiovascular autonomic function testing (cAFT) and electro-diagnostic studies (EDS

  5. Pathogenesis of Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Amir Aslam

    2014-01-01

    Full Text Available The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain.

  6. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  7. Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy.

    Science.gov (United States)

    Marshall, Andrew G; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N; Ponirakis, Georgios; Fineman, Mark S; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jeziorska, Maria; Jolivalt, Corinne G; Boulton, Andrew J M; Efron, Nathan; Calcutt, Nigel A; Malik, Rayaz A

    2017-02-15

    Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5HT2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy when compared to healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fibre pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help to identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.

  8. Epidermal Nerve Fiber Quantification in the Assessment of Diabetic Neuropathy

    Science.gov (United States)

    Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

    2008-01-01

    Summary Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy. PMID:18384843

  9. Autonomic neuropathy in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Alberto eVerrotti

    2014-12-01

    Full Text Available Diabetic autonomic neuropathy (DAN is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy (CAN defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis and management of DAN, with some mention to childhood and adolescent population.

  10. Central nervous system involvement in diabetic neuropathy.

    Science.gov (United States)

    Selvarajah, Dinesh; Wilkinson, Iain D; Davies, Jennifer; Gandhi, Rajiv; Tesfaye, Solomon

    2011-08-01

    Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes. Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system involvement. Recent advances in neuroimaging methods detailed in this review have led to a better understanding and refinement of how diabetic neuropathy affects the central nervous system. Recognition that diabetic neuropathy is, in part, a disease that affects the whole nervous system is resulting in a critical rethinking of this disorder, opening a new direction for further research.

  11. Electrodiagnostic testing in diabetic neuropathy: Which limb?

    Science.gov (United States)

    Rota, E; Cocito, D

    2015-10-01

    Electrodiagnosis of subclinical diabetic neuropathies by nerve conduction studies remains challenging. The question arises about which nerves should be tested and what the best electrodiagnostic protocol to make an early diagnosis of diabetic neuropathies would be. On the basis of our findings and other evidence, which highlighted the remarkable prevalence of electrophysiological abnormalities in nerve conduction studies of the upper limbs, often in the presence of normal lower limb conduction parameters, we suggest that both ulnar and median nerves, in their motor and sensitive component, should be the two target nerves for electrodiagnostic protocols in diabetic neuropathies.

  12. The diabetic neuropathies: practical and rational therapy.

    Science.gov (United States)

    Singleton, J Robinson; Smith, A Gordon

    2012-07-01

    Diabetes is associated with a variety of chronic and acute neuropathies. In this article, the authors summarize the clinical features of the most common diabetic neuropathies, focusing on those for which therapy is available or under active investigation. Distal symmetric polyneuropathy (DSP) is the most common form. Potential treatments for DSP are discussed in four broad themes: (1) medication and lifestyle therapy to improve hyperglycemia, insulin resistance, and attendant features of metabolic syndrome, including obesity and dyslipidemia; (2) pharmacologic therapy to alter neuropathy natural history aimed at rational targets from known pathophysiology; (3) symptomatic relief of neuropathic pain; and (4) treatment to prevent complications of neuropathy, including stasis ulcers and falls. The approach to the most common acute diabetic neuropathies is also reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Pharmacological Treatment Of Diabetic Peripheral Neuropathy

    OpenAIRE

    2015-01-01

    Pain modulation is a key treatment goal for diabetic peripheral neuropathy patients. Guidelines have recommended antidepressant, anticonvulsant, analgesic, and topical medications—both approved and off-label—to reduce pain in this population.

  14. Diabetic neuropathy part 1: overview and symmetric phenotypes.

    Science.gov (United States)

    Pasnoor, Mamatha; Dimachkie, Mazen M; Kluding, Patricia; Barohn, Richard J

    2013-05-01

    Diabetes is the most common cause of neuropathy in United States and neuropathies are the most common complication of diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Symptoms usually include numbness, tingling, pain, and weakness. Dizziness with postural changes can be seen with autonomic neuropathy. Metabolic, vascular, and immune theories have been proposed for the pathogenesis of diabetic neuropathy. Axonal damage and segmental demyelination can be seen with diabetic neuropathies. Management of diabetic neuropathy should begin at the initial diagnosis of diabetes and mainly requires tight and stable glycemic control.

  15. The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

    Science.gov (United States)

    Chowdhury, Subir K Roy; Smith, Darrell R; Fernyhough, Paul

    2013-03-01

    Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). This article attempts to relate these findings to the development of critical neuropathological hallmarks of the disease. Recent work reveals that hyperglycemia in diabetes triggers nutrient excess in neurons that, in turn, mediates a phenotypic change in mitochondrial biology through alteration of the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling axis. This vital energy sensing metabolic pathway modulates mitochondrial function, biogenesis and regeneration. The bioenergetic phenotype of mitochondria in diabetic neurons is aberrant due to deleterious alterations in expression and activity of respiratory chain components as a direct consequence of abnormal AMPK/PGC-1α signaling. Utilization of innovative respirometry equipment to analyze mitochondrial function of cultured adult sensory neurons from diabetic rodents shows that the outcome for cellular bioenergetics is a reduced adaptability to fluctuations in ATP demand. The diabetes-induced maladaptive process is hypothesized to result in exhaustion of the ATP supply in the distal nerve compartment and induction of nerve fiber dissolution. The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich

  16. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    Directory of Open Access Journals (Sweden)

    Md. Shahidul Islam

    2013-01-01

    Full Text Available Diabetic or peripheral diabetic neuropathy (PDN is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat models, conventional or genetically modified or high-fat diet-fed C57BL/Ks (db/db mice models, streptozotocin-induced C57BL6/J and ddY mice models, Chinese hamster neuropathic model, rhesus monkey PDN model, spontaneously diabetic WBN/Kob rat model, L-fucose-induced neropathic rat model, partial sciatic nerve ligated rat model, nonobese diabetic (NOD mice model, spontaneously induced Ins2 Akita mice model, leptin-deficient (ob/ob mice model, Otsuka Long-Evans Tokushima Fatty (OLETF rat model, surgically-induced neuropathic model, and genetically modified Spontaneously Diabetic Torii (SDT rat model, none of which are without limitations. An animal model of diabetic or PDN should mimic the all major pathogeneses of human diabetic neuropathy. Hence, this review comparatively evaluates the animal models of diabetic and PDN which are developed since 1960s with their advantages and disadvantages to help diabetic research groups in order to more accurately choose an appropriate model to meet their specific research objectives.

  17. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted......NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...

  18. In vivo evaluation of a rat model for diabetic neuropathies

    OpenAIRE

    Wauters, Shana

    2007-01-01

    Diabetic peripheral neuropathy is considered to be a long-term complication of Diabetes Mellitus. This neuropathy is the most common form of peripheral neuropathy in the Western world and develops in about 50% of diabetes patients affected with either type I or type II diabetes. Despite advances in understanding metabolic causes of diabetic peripheral neuropathy, specific treatments against this complications are far from being used in therapy options. In this study we have eva...

  19. Mechanisms of diabetic neuropathy: Schwann cells.

    Science.gov (United States)

    Mizisin, Andrew P

    2014-01-01

    As ensheathing and secretory cells, Schwann cells are a ubiquitous and vital component of the endoneurial microenvironment of peripheral nerves. The interdependence of axons and their ensheathing Schwann cells predisposes each to the impact of injury in the other. Further, the dependence of the blood-nerve interface on trophic support from Schwann cells during development, adulthood, and after injury suggests these glial cells promote the structural and functional integrity of nerve trunks. Here, the developmental origin, injury-induced changes, and mature myelinating and nonmyelinating phenotypes of Schwann cells are reviewed prior to a description of nerve fiber pathology and consideration of pathogenic mechanisms in human and experimental diabetic neuropathy. A fundamental role for aldose-reductase-containing Schwann cells in the pathogenesis of diabetic neuropathy, as well as the interrelationship of pathogenic mechanisms, is indicated by the sensitivity of hyperglycemia-induced biochemical alterations, such as polyol pathway flux, formation of reactive oxygen species, generation of advanced glycosylation end products (AGEs) and deficient neurotrophic support, to blocking polyol pathway flux.

  20. A REVIEW ON DIABETIC NEUROPATHY AND NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Mohd. Muneer Ahamed

    2012-01-01

    Full Text Available Diabetes is a major public health problem. Diabetes mellitus now affects large number of people in many developing countries than western countries where only two or three percent of the population is affected. With on estimated 33 million people in India alone affected by diabetes. It is a major epidemic of the twentieth century. Diabetes is a chronic disorder, which is associated with obesity, hypertension, advancing age, accumulation of harmful agents in the vascular endothelium causing development of microangiopathies or micro vascular complications. These complications include peripheral neuropathy, nephropathy and retinopathy, which cause early death and increased morbidity. These complications vary in prevalence in different populations depending on various factors such as genetic predisposition and ethnicity. Besides these complications cardiovascular changes are also occurring. Peripheral neuropathy (PN is characterized by pain, numbness, and tingling in the extremities with slow nerve conduction. Up to 50% of all patients with diabetes develop neuropathy and the prevalence of painful neuropathy ranges from 10 to 20% of patients with diabetes. Diabetic nephropathy is characterized by increased urinary protein, loss of renal function, excessive deposition of extracellular matrix proteins in the mesangium, and clear cytoplasm of the proximal tubular epithelial cells due to excessive reabsorbed glycogen. Evaluation of diabetes and its complications is very essential for proper control and prevention of the disease associated complications.

  1. Anesthesia Management in Diabetic Cardiovascular Autonomic Neuropathy

    OpenAIRE

    Feride Karacaer

    2016-01-01

    Cardiovascular autonomic neuropathy is frequently observed in patients with diabetes mellitus and encompasses damage to the autonomic nerve fibers, resulting in abnormalities in heart rate control and vascular dynamics. There is an increased mortality and morbidity rate among these patients. A series of cardiovascular reflex tests known as Ewing's battery tests are used for diagnosis cardiac autonomic neuropathy and provide valuable information to the clinical assessment of these patients. As...

  2. Relief of diabetic neuropathy with fluoxetine.

    Science.gov (United States)

    Theesen, K A; Marsh, W R

    1989-01-01

    A 31-year-old woman with advanced diabetes mellitus with secondary autonomic and peripheral neuropathy was admitted for treatment of major depression. Previous therapy with desipramine resulted in exacerbation of the patient's orthostatic hypotension. After admission to the psychiatric facility she was initially stabilized medically and treated with psychotherapy. Subsequent treatment with low-dose fluoxetine 5 mg resulted in a decrease of the patient's diabetic neuropathy pain. Further increases in the fluoxetine dosage resulted in improvement of her depression and increased pain relief. Therapy with fluoxetine did not result in exacerbation of the orthostatic hypotension. This preliminary case report indicates that fluoxetine may be an alternative to the tricyclic antidepressants and trazodone in the treatment of diabetic peripheral neuropathy.

  3. Ocular neuropathy in peripheral neuropathies.

    Science.gov (United States)

    Evliyaoglu, Ferhat; Karadag, Remzi; Burakgazi, Ahmet Z

    2012-11-01

    Ocular movements and coordination require complex and integrated functions of somatic and autonomic nervous systems. Neurological disorders affecting these nervous systems may cause ocular dysfunction involving extraocular muscles and pupils. In this article, the prevalence, clinical presentations, and management of ocular neuropathy related to certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome (GBS), chronic inflammatory neuropathies, human immunodeficiency virus (HIV)-associated neuropathy, and hereditary neuropathies, are examined in detail. Copyright © 2012 Wiley Periodicals, Inc.

  4. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

    Science.gov (United States)

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718

  5. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    Science.gov (United States)

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-05-27

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.

  6. Painful diabetic neuropathies, cases report and diagnostic criteria

    OpenAIRE

    Marco Lacerenza

    2006-01-01

    Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pai...

  7. Treatment of Diabetic Neuropathy- Principles and Methods

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Diabetic neuropathy (DN) is one of the common complications of diabetes mellitus (DM), its incidence can be as high as over 90%. The lesion can involve the sensory, motor and vegetative nerves. As a whole, the lesion can be divided into symmetric multiple neuropathy and asymmetric single neuropathy. Because the pathogenesis of the disease is not clear, no specific therapy is available so far. Besides control of blood sugar level, vitamin B, vasodilators and analgesics are often used in Western medicine for expectant treatment. Basic studies on chronic complications of DM show that aldose reductase and non-enzymatic glycosylation of protein are factors initiating the pathological changes, inhibitors against them have been tested in experimental studies and proved effective. Unfortunately, they are not used clinically due to severe side effects. Screening for herbal drugs to treat DN is still a popular trend in the TCM circle.

  8. Neuropathy and Diabetic Foot Syndrome.

    Science.gov (United States)

    Volmer-Thole, Maren; Lobmann, Ralf

    2016-06-10

    Diabetic foot ulceration is a serious complication of diabetes mellitus worldwide and the most common cause of hospitalization in diabetic patients. The etiology of diabetic foot ulcerations is complex due to their multifactorial nature; in the pathophysiology of diabetic foot ulceration polyneuropathy is important. Proper adherence to standard treatment strategies and interdisciplinary cooperation can reduce the still high rates of major amputations.

  9. Role of nitrosative and oxidative stress in neuropathy in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Marwan S Al-Nimer

    2012-01-01

    Full Text Available Objectives : Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy. Materials and Methods : Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS, neuropathy impairment score in the lower leg (NIS-LL, and nerve conduction velocity of sensory (ulnar and sural and motor (ulnar and common peroneal nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins. Results: The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components, sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy. Conclusion: It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy.

  10. Painful diabetic neuropathies, cases report and diagnostic criteria

    Directory of Open Access Journals (Sweden)

    Marco Lacerenza

    2006-12-01

    Full Text Available Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pains may originate from different nerve injuries, and harbour different pathophysiological mechanisms. A comprehensive and accurate evaluation of clinical and neurophysiological abnormalities in painful diabetic neuropathies provides insight on the pathophysiological mechanism and directs the clinician towards rational treatment strategies.

  11. An early diagnostic tool for diabetic peripheral neuropathy in rats

    NARCIS (Netherlands)

    S. Kambiz (Shoista); J.W. van Neck (Han); S.G. Cosgun (Saniye G.); M.H.N. van Velzen (M. H N); J.A.M.J.L. Janssen (Joseph); Avazverdi, N. (Naim); S.E.R. Hovius (Steven); E.T. Walbeehm (Erik)

    2015-01-01

    textabstractThe skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study w

  12. An early diagnostic tool for diabetic peripheral neuropathy in rats

    NARCIS (Netherlands)

    Kambiz, S.; Neck, J.W. van; Cosgun, S.G.; Velzen, M.H. van; Janssen, J.A.M.; Avazverdi, N.; Hovius, S.E.; Walbeehm, E.T.

    2015-01-01

    The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to invest

  13. The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy

    DEFF Research Database (Denmark)

    Østergaard, Leif; Finnerup, Nanna B.; Terkelsen, Astrid J.

    2015-01-01

    Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate...... the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early...... blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic...

  14. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability

    Directory of Open Access Journals (Sweden)

    Kevin Farmer

    2012-01-01

    Full Text Available KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  15. KU-32, a novel drug for diabetic neuropathy, is safe for human islets and improves in vitro insulin secretion and viability.

    Science.gov (United States)

    Farmer, Kevin; Williams, S Janette; Novikova, Lesya; Ramachandran, Karthik; Rawal, Sonia; Blagg, Brian S J; Dobrowsky, Rick; Stehno-Bittel, Lisa

    2012-01-01

    KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  16. Anesthesia Management in Diabetic Cardiovascular Autonomic Neuropathy

    Directory of Open Access Journals (Sweden)

    Feride Karacaer

    2016-06-01

    Full Text Available Cardiovascular autonomic neuropathy is frequently observed in patients with diabetes mellitus and encompasses damage to the autonomic nerve fibers, resulting in abnormalities in heart rate control and vascular dynamics. There is an increased mortality and morbidity rate among these patients. A series of cardiovascular reflex tests known as Ewing's battery tests are used for diagnosis cardiac autonomic neuropathy and provide valuable information to the clinical assessment of these patients. As anesthesia has a major influence on perioperative autonomic function, the interplay between cardiovascular autonomic neuropathy and anesthesia may result in unexpected haemodynamic instability during surgery and postoperative recovery. A comprehensive preoperative assessment and perioperative cautious monitoring are necessary for successful anesthesia management. [Archives Medical Review Journal 2016; 25(2.000: 140-151

  17. Fuzzy expert system for diagnosing diabetic neuropathy.

    Science.gov (United States)

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-02-15

    To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists' perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients.

  18. The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy.

    Science.gov (United States)

    Østergaard, Leif; Finnerup, Nanna B; Terkelsen, Astrid J; Olesen, Rasmus A; Drasbek, Kim R; Knudsen, Lone; Jespersen, Sune N; Frystyk, Jan; Charles, Morten; Thomsen, Reimar W; Christiansen, Jens S; Beck-Nielsen, Henning; Jensen, Troels S; Andersen, Henning

    2015-04-01

    Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.

  19. Validity of the neurological examination in diagnosing diabetic peripheral neuropathy.

    Science.gov (United States)

    Höliner, Isabella; Haslinger, Vera; Lütschg, Jürg; Müller, Guido; Barbarini, Daniela Seick; Fussenegger, Jörg; Zanier, Ulrike; Saely, Christoph H; Drexel, Heinz; Simma, Burkhard

    2013-09-01

    The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients.

  20. Cardiovascular autonomic neuropathy in the diabetic patients.

    Directory of Open Access Journals (Sweden)

    Maria Eugenia Niño Mantilla

    2007-11-01

    Full Text Available the dysfunction of the autonomic nervous system is a serious problem in diabetic patients. The cardiovacular autonomic neuropathy is the most important autonomic dysfuntion for it´s implication in the increasesof the mortality rate in diabetis patients. tis ethiopatogenesis is the result of a multifactorial process caused by chronic hyperglycemia, ending up in damage of the autonomic fibers thet innervate the heart and blood vessels, leading to dysfuntional hearth rate control and abnormal vascular dynamics. the associated clinical manifestations include orthotatic hypotension, excecise intolerance, intraoperative cardiovascular liability and silent myocardial ischemia. Being important its recognition, quantitative test to evaluate the cardiovascular funtion, to value its evolution and the effects of the treatment ahould be done, being the most used, the hearth rate response to standing test, and teh valsalva maneuver. the handling of this entity is done improving control of glucose blood levels its the most effective way to prevent the cardiovascular autonomic neuropathy in the diabetic patients.

  1. Diabetic neuropathy part 2: proximal and asymmetric phenotypes.

    Science.gov (United States)

    Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J

    2013-05-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is the most common type of diabetic neuropathy, many other subtypes have been defined since the 1800s, including proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control. Immunotherapies have been tried in some of these conditions however are controversial.

  2. Effect of Tinospora cordifolia on experimental diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Pratibha D Nadig

    2012-01-01

    Conclusions: Tinospora cordifolia prevents the hyperalgesia in experimental diabetic neuropathy. It has an aldose reductase inhibitory activity in-vitro which may contribute to the beneficial effects.

  3. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    OpenAIRE

    Md. Shahidul Islam

    2013-01-01

    Diabetic or peripheral diabetic neuropathy (PDN) is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat...

  4. Computer aided diagnosis of diabetic peripheral neuropathy

    Science.gov (United States)

    Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang

    2014-03-01

    Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.

  5. Plasma dihydroxyphenylglycol (DHPG) as an index of diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Christensen, N J; Dejgaard, Anders; Hilsted, J

    1988-01-01

    Forearm venous plasma noradrenalin and dihydroxyphenylglycol (DHPG) concentrations were measured in eight diabetic patients with and eight diabetic patients without neuropathy. Plasma noradrenalin was on average the same in patients with and without neuropathy and correlated to serum creatinine....... Plasma DHPG concentrations were significantly reduced in patients with autonomic neuropathy as compared to patients without neuropathy (P less than 0.05). A low plasma DHPG/noradrenalin ratio in forearm venous blood identified all patients with autonomic neuropathy except one (P less than 0...

  6. Autonomic neuropathy and diabetic foot ulceration.

    Science.gov (United States)

    Edmonds, M E; Nicolaides, K H; Watkins, P J

    1986-01-01

    Autonomic function was studied in three groups of insulin-dependent diabetic patients. Heart rate changes during deep breathing and on standing were significantly less in 28 patients with a recent history of foot ulceration compared with 40 patients with peripheral neuropathy but without ulceration (p less than 0.001) and 54 patients without neuropathy (p less than 0.001). Sympathetic function was assessed in 36 of these patients from peripheral arterial diastolic flow patterns obtained by Doppler ultrasound measurements and expressed as the pulsatility index (PI). Patients with a history of ulceration (n = 10) showed considerably increased diastolic flow (PI = 4.28 +/- 0.53, mean +/- S.E.M.) compared with 12 neuropathic patients with no history of ulceration (PI = 7.80 +/- 0.68, p less than 0.002) and 14 patients without neuropathy (PI = 9.55 +/- 0.89, p less than 0.002). Severely abnormal autonomic function occurs in association with neuropathic foot ulceration, but patients without ulcers have lesser degrees of autonomic neuropathy, thus a causal relationship has not been established.

  7. Beneficial effect of the Ca2+ antagonist, nimodipine, on existing diabetic neuropathy in the BB/Wor rat

    OpenAIRE

    Gispen, W.H.; Kappelle, A. C.; Biessels, G.J.; Bravenboer, B.; Buren, T. van; Traber, J.; de Wildt, D J

    1994-01-01

    1. Neuropathy is a frequently diagnosed complication of diabetes mellitus. Effective pharmacotherapy is not available. 2. The spontaneously diabetic BB/Wor rats develop secondary complications like neuropathy as do human diabetic patients. 3. BB/Wor rats treated with insulin via a subcutaneous implant show a significant impairment of sensory and motor nerve conduction velocity 6 weeks after the onset of diabetes mellitus. 4. Intraperitoneal treatment of diabetic BB/Wor rats with the Ca2+ anta...

  8. Tolerating diabetes: an alternative therapeutic approach for diabetic neuropathy

    OpenAIRE

    2010-01-01

    It is becoming apparent that a number of pathogenic mechanisms contribute to diabetic neuropathy, so that therapeutic interventions that target one particular mechanism may have limited success. A recently published preclinical study has adopted an alternative approach by using a novel small molecule to induce heat-shock protein 70. This confers upon neurons, and perhaps other cells of the nervous system, the ability to better tolerate the diverse stresses associated with diabetes rather than...

  9. Tolerating diabetes: an alternative therapeutic approach for diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Nigel A Calcutt

    2010-09-01

    Full Text Available It is becoming apparent that a number of pathogenic mechanisms contribute to diabetic neuropathy, so that therapeutic interventions that target one particular mechanism may have limited success. A recently published preclinical study has adopted an alternative approach by using a novel small molecule to induce heat-shock protein 70. This confers upon neurons, and perhaps other cells of the nervous system, the ability to better tolerate the diverse stresses associated with diabetes rather than intervening in their production.

  10. Tolerating diabetes: an alternative therapeutic approach for diabetic neuropathy.

    Science.gov (United States)

    Calcutt, Nigel A

    2010-09-09

    It is becoming apparent that a number of pathogenic mechanisms contribute to diabetic neuropathy, so that therapeutic interventions that target one particular mechanism may have limited success. A recently published preclinical study has adopted an alternative approach by using a novel small molecule to induce heat-shock protein 70. This confers upon neurons, and perhaps other cells of the nervous system, the ability to better tolerate the diverse stresses associated with diabetes rather than intervening in their production.

  11. Fuzzy expert system for diagnosing diabetic neuropathy

    Science.gov (United States)

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-01-01

    AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists’ perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). CONCLUSION The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients. PMID:28265346

  12. CIDP and other inflammatory neuropathies in diabetes - diagnosis and management.

    Science.gov (United States)

    Rajabally, Yusuf A; Stettner, Mark; Kieseier, Bernd C; Hartung, Hans-Peter; Malik, Rayaz A

    2017-09-15

    Distal symmetric polyneuropathy (DSPN) is the most common neuropathy to occur in diabetes mellitus. However, patients with diabetes can also develop inflammatory neuropathies, the most common and most treatable of which is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Whether diabetes is a risk factor for CIDP remains under debate. Early studies suggested that patients with diabetes were at increased risk of CIDP, but epidemiological studies failed to confirm the association, and subsequent data have re-opened the debate. Inadequate interpretation of investigations and differentials between CIDP and other neuropathies that can occur in diabetes, such as DSPN, diabetic radiculoplexus neuropathies and vasculitic multiple mononeuropathy, might mean that CIDP is under-recognized. Despite a response rate of >80% to first-line therapies for CIDP in patients with or without diabetes, those with diabetes often present with greater disability owing to late referral and axonal pathology attributed to DSPN. The increasing worldwide prevalence of diabetes creates an urgent need to improve identification of potentially treatable neuropathies, such as CIDP. In this Review, we consider the features of CIDP in patients with diabetes, and discuss how these features can be used to differentiate the condition from other neuropathies. We also review the management options for CIDP and other inflammatory neuropathies in patients with diabetes.

  13. Potential risk factors for diabetic neuropathy: a case control study

    Directory of Open Access Journals (Sweden)

    Nooraei Mahdi

    2005-12-01

    Full Text Available Abstract Background Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. Methods In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography. The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. Results Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, Conclusion In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

  14. Decreased myocardial perfusion reserve in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Taskiran, Mustafa; Fritz-Hansen, Thomas; Rasmussen, Verner

    2002-01-01

    The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline...... conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN-) and 10 healthy control subjects. Baseline myocardial perfusion index (K...... blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate...

  15. Early diabetic neuropathy: Triggers and mechanisms

    Institute of Scientific and Technical Information of China (English)

    Maxim Dobretsov; Dmitry Romanovsky; Joseph R Stimers

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients, It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well.It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.

  16. Oxidative Injury and Neuropathy in Diabetes and Impaired Glucose Tolerance

    OpenAIRE

    Russell, James W.; Berent-Spillson, Alison; Vincent, Andrea M.; Freimann, Catherine L.; Sullivan, Kelli A.; Feldman, Eva L.

    2008-01-01

    Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor acti...

  17. Diabetic peripheral neuropathy: current perspective and future directions.

    Science.gov (United States)

    Singh, Randhir; Kishore, Lalit; Kaur, Navpreet

    2014-02-01

    Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy.

  18. Wherefore Art Thou, O Treatment for Diabetic Neuropathy?

    Science.gov (United States)

    Malik, R A

    2016-01-01

    As of March 2016, we continue to advocate the diagnosis of diabetic neuropathy using a simple foot examination or monofilament, which identifies only those with severe neuropathy and hence risk of foot ulceration. Given the fact that the 5-year mortality rate of diabetic patients with foot ulceration is worse than that of most common cancers, surely we should be identifying patients at an earlier stage of neuropathy to prevent its progression to a stage with such a high mortality? Of course, we lament that there is no licensed treatment for diabetic neuropathy. Who is to blame? As researchers and carers, we have a duty of care to our patients with diabetic neuropathy. So, we have to look forward not backwards, and move away from our firmly entrenched views on the design and conduct of clinical trials for diabetic neuropathy. Relevant organizations such as Neurodiab, the American Diabetes Association and the Peripheral Nerve Society have to acknowledge that they cannot continue to endorse a bankrupt strategy. The FDA needs an open and self-critical dialogue with these organizations, to give pharmaceutical companies at least a fighting chance to deliver effective new therapies for diabetic neuropathy.

  19. Medial arterial calcification in diabetes and its relationship to neuropathy

    DEFF Research Database (Denmark)

    Jeffcoate, W J; Rasmussen, Lars Melholt; Hofbauer, L C

    2009-01-01

    Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification...... factor linked to the development of arterial calcification is distal symmetrical neuropathy; indeed, it has been suggested that neuropathy explains the distal distribution of arterial calcification in diabetes. It has also been suggested that the link with neuropathy results from loss of neuropeptides......, such as calcitonin gene-related peptide, which are inherently protective. The association between distal symmetrical neuropathy and calcification of the arterial wall highlights the fact that neuropathy may be an independent risk factor for cardiovascular mortality....

  20. Diabetic and non-diabetic lumbosacral radiculoplexus neuropathy

    Directory of Open Access Journals (Sweden)

    Bhanushali Minal

    2008-01-01

    Full Text Available Background: Lumbosacral radiculoplexus neuropathy (LRPN originally described in diabetic patients is a distinct clinical condition characterized by debilitating pain, weakness and atrophy most commonly affecting the proximal thigh muscles asymmetrically. The syndrome is usually monophasic and preceded by significant weight loss (at least more than 10 lbs. Though a self-limited condition, recovery is gradual with some residual weakness. Recent advances and research has provided new insights in the pathogenesis and thereby management of this syndrome. In this paper, we review the clinical and diagnostic features as well as discuss recent insights and treatment strategies along with our experience in the management of patients with diabetic and non-diabetic LRPN. Materials and Methods: Literature in English published between 1953 and 2008 was searched in the MEDLINE and Pubmed database, maintained by the US National library of medicine and National institutes of health, using key words of diabetic amyotrophy, lumbosacral radiculoplexus neuropathy, diabetic proximal neuropathy, diabetic radiculopathy and diabetic lumbosacral plexopathy. In addition, literature reported in various textbooks on peripheral neuropathy was reviewed as well. Observation: The diagnosis relies mostly on clinical suspicion and characteristic electromyographic findings. The exact pathogenesis of the illness remains unknown, but there seems to be a component of immune-mediated inflammatory microvasculitis which causes secondary ischemia of the lumbosacral plexus. This has prompted a trial of immunosuppressive agents (like steroids with an attempt to alter the course of the illness. A few reports have noted that immunosuppression when instituted early in the course of the illness (within three months of symptom onset may hasten the recovery and improve symptoms. Conclusion: Though the exact mechanism of LRPN in diabetic and non-diabetic patients remains unknown, new evidence

  1. Chewing the fat: genetic approaches to model dyslipidemia-induced diabetic neuropathy in mice.

    Science.gov (United States)

    Guilford, B L; Wright, D E

    2013-10-01

    Emerging clinical evidence now suggests that dyslipidemia may be strongly linked with the development and progression of neuropathy in diabetic patients, and dyslipidemia is considered an important risk factor for the development of diabetic neuropathy. However, because of important species differences, current animal models fall short of accurately replicating human diabetic dyslipidemia. Rodents resist expansion in low-density lipoprotein cholesterol (LDL-C) and typically maintain or increase high-density lipoprotein cholesterol (HDL-C), despite prolonged high-fat feeding. Here, we discuss the findings of Hinder et al., in which they utilized novel genetic experimental approaches to develop a diabetic mouse model with human-like dyslipidemia. The authors created a mouse with an apolipoprotein E (ApoE) knockout in conjunction with a leptin receptor mutation. A triple mutant mouse with both ApoE and apolipoprotein B48 knockout and leptin deficiency was also created in an effort to generate a model of diabetic dyslipidemia that better mimics the human condition. The long-term goal of these studies is to develop more faithful models to address how hyperglycemia and hyperlipidemia may drive the development and progression of neuropathy. Hinder and colleagues were successful at creating a diabetic mouse model with severe hypertriglyceridemia, hypercholesterolemia, and a significant increase in the total cholesterol to HDL-C ratio. This work was successful in establishing a model of diabetic dyslipidemia that more closely emulates the poor lipid profile observed in human diabetic patients with neuropathy. This commentary will also review current models used to study the effects of dyslipidemia on diabetic neuropathy and highlight a proposed mechanism for the role of dyslipidemia in the pathogenesis of diabetic neuropathy.

  2. Sensory manifestations of diabetic neuropathies: anatomical and clinical correlations.

    Science.gov (United States)

    Kazamel, Mohamed; Dyck, Peter J

    2015-02-01

    Diabetes mellitus is among the most common causes of peripheral neuropathy worldwide. Sensory impairment in diabetics is a major risk factor of plantar ulcers and neurogenic arthropathy (Charcot joints) causing severe morbidity and high health-care costs. To discuss the different patterns of sensory alterations in diabetic neuropathies and their anatomical basis. Literature review. Review of the literature discussing different patterns of sensory impairment in diabetic neuropathies. The different varieties of diabetic neuropathies include typical sensorimotor polyneuropathy (lower extremity predominant, length-dependent, symmetric, sensorimotor polyneuropathy presumably related to chronic hyperglycemic exposure, and related metabolic events), entrapment mononeuropathies, radiculoplexus neuropathies related to immune inflammatory ischemic events, cranial neuropathies, and treatment-related neuropathies (e.g. insulin neuritis). None of these patterns are unique for diabetes, and they can occur in nondiabetics. Sensory alterations are different among these prototypic varieties and are vital in diagnosis, following course, treatment options, and follow-up of treatment effects. Diabetic neuropathies can involve any segment of peripheral nerves from nerve roots to the nerve endings giving different patterns of abnormal sensation. It is the involvement of small fibers that causes positive sensory symptoms like pain early during the course of disease, bringing subjects to physician's care. This article emphasizes on the fact that diabetic neuropathies are not a single entity. They are rather different varieties of conditions with more or less separate pathophysiological mechanisms and anatomical localization. Clinicians should keep this in mind when assessing patients with diabetes on the first visit or follow-up. © The International Society for Prosthetics and Orthotics 2014.

  3. Pharmachologic Treatment of Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Gul Mete Civelek

    2016-01-01

    Full Text Available Neuropathic pain is defined as %u201Cpain occuring as a direct result of a disease or lesion directly affecting somato-sensorial system%u201D. Painful diabetic neuropathy (PDN is a serious complication impairing quality of life of patients. Researchs show that PDN affects approximately 16% of patients with diabetes. An important part of the PDN patients (39% remain without treatment. The diagnosis of neuropathic pain is a clinical diagnosis. Pain can be described by patients as burning, throbbing, numbness, tingling, anesthetic, pins and needles or blunt pain. Neuropathic pain is accompanied by sensory disorders such as dysesthesia, allodynia (pain heard by a stimulus not creating pain or hyperalgesia ( reduction of pain threshold for a painful stimulus. PDN develops in almost half of diabetic patients within the first ten years of diabetes. Over time, muscle loss, decreased deep tendon reflexes and trophic skin changes can be observed. Treatment guidelines agree that some agents such as pregabalin, gabapentin, tricyclic antidepressants should be preferred in the first line and have controversial proposals for some agents such as duloxetine. This shows the need for more research on the issue. It is important for all physicians dealing with pain, to recognize PDN and prefer evidence-based treatment approaches for patient benefit. In this review pharmacological treatment of PDN is discussed in light of current research and treatment guidelines.

  4. Contribution of mitochondria to pain in diabetic neuropathy.

    Science.gov (United States)

    Hernández-Beltrán, Natalia; Moreno, Carlos B; Gutiérrez-Álvarez, Angela María

    2013-01-01

    Diabetes is a metabolic disease affecting approximately 300 million people worldwide. Neuropathy is one of its frequent complications, and may affect sensory, motor, and autonomic nerves. Its pathophysiology has not fully been elucidated. Several hypotheses have been proposed, and mitochondria have been suggested to play a significant role. This article reviews the mechanisms involved in mitochondrial dysfunction and development of diabetic neuropathy, consisting mainly of oxidative and inflammatory stress, changes in intracellular calcium regulation, apoptotic processes, and changes in mitochondrial structure and function that may lead to development of diabetic neuropathy.

  5. Prevalence of diabetic autonomic neuropathy measured by simple bedside tests

    DEFF Research Database (Denmark)

    Dyrberg, Torben Bech; Benn, Jette; Christiansen, J S

    1981-01-01

    To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beat-to-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate response....... The prevalence of diabetic autonomic neuropathy in the whole diabetic population indicated by abnormal response in beat-to-beat variation during forced respiration was 27%. Diabetic autonimic neuropathy increased in frequency with duration of disease. Patients with nephropathy or proliferative retinopathy had...... a significantly higher prevalence of diabetic autonomic neuropathy as indicated by abnormal beat-to-beat variation during forced respirations (p less than 0.01) than patients without these complications....

  6. Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Richter, E; Madsbad, S

    1987-01-01

    . To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...... with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients...

  7. status and insulin resistance in diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Taslima Akter

    2016-12-01

    Full Text Available Background: Complication of diabetes mellitus includes peripheral neuropathy which causes ischemic foot ulceration. Hyperglycemia and insulin resistance may accelerate the development of diabetic peripheral neuropathy. Objective: To assess the glycaemic status and insulin resistance for development of peripheral neuropathy in type 2 diabetes mellitus. Methods: This control case control study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2014 to June 2015. A total number of 150 Type 2 diabetic patients of both sexes were selected with age ranging 40 to 50 years. Among them, 75 patients with peripheral neuropathy were included in study group and 75 patients without peripheral neuropathy were control. For evaluation of glycaemic status, fasting serum glucose (FSG, Glycosylated hemoglobin (HbA1c and to calculate insulin resistance by homeostatic model assessment for insulin resistance (HOMA-IR, fasting serum insulin (FSI, were estimated. For statistical analysis, unpaired Student’s ‘t’ test was done. Results: In this study, significant increase in FSG, HbA1c, FSI, HOMA-IR were found in diabetic subjects with peripheral neuropathy in comparison to control group. Conclusion: From the study results, it is concluded that poor glycaemic control and greater insulin resistance may be associated with diabetic peripheral neuropathy.

  8. Strategies and Methods for the Treatment of Diabetic Neuropathy Using Integrative Chinese and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    HENG Xian-pei

    2008-01-01

    @@ Diabetic neuropathy (DN) is the most common metabolic neuropathy in clinics, not only in diabetes patients (>60%), but also in pre-diabetic (8%) and normal persons (5%)(1). Its pathogenesis has not been fully understood up to now.

  9. PGC-1α regulation of mitochondrial degeneration in experimental diabetic neuropathy.

    Science.gov (United States)

    Choi, Joungil; Chandrasekaran, Krish; Inoue, Tatsuya; Muragundla, Anjaneyulu; Russell, James W

    2014-04-01

    Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1α and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1α (-/-) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1α (-/-) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1α causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1α in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1α in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1α function may be an attractive approach for treatment of diabetic neuropathy.

  10. Surgical approach to lower extremity nerve decompression in the patient with diabetic neuropathy

    NARCIS (Netherlands)

    Dellon, A.L.

    2007-01-01

    Neuropathy associated with Diabetes is increasing at epidemic rates throughout the world. Traditionally, this neuropathy causes loss of protective sensation leading to ulceration, infection , and amputation. Even with good glycemic control, this neuropathy is still considered progressive and irrever

  11. Nrf2: a potential therapeutic target for diabetic neuropathy.

    Science.gov (United States)

    Kumar, Anil; Mittal, Ruchika

    2017-03-28

    Different aspects involved in pathophysiology of diabetic neuropathy are related to inflammatory and apoptotic pathways. This article summarizes evidence that Nrf2 acts as a bridging link in various inflammatory and apoptotic pathways impacting progression of diabetic neuropathy. Nrf2 is involved in expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element (ARE) binding site. Under normal conditions, Nrf2 is inactive and remains in the cytosol. Hyperglycemia is a strong stimulus for oxidative stress and inflammation that downregulates the activity of Nrf2 through various neuroinflammatory pathways. Acute hyperglycemia increases the expression of Nrf2, but persistent hyperglycemia decreases its expression. This downregulation of Nrf2 causes various microvascular changes, which result in diabetic neuropathy. The key contribution of Nrf2 in progression of diabetic neuropathy has been summarized in the article. Despite involvement of Nrf2 in progression of diabetic neuropathy, targeting Nrf2 activators as a therapeutic potential will provide important new insights into the ways that influence treatment of diabetic neuropathy.

  12. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    Directory of Open Access Journals (Sweden)

    Heung Yong Jin

    2015-12-01

    Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

  13. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    Science.gov (United States)

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  14. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Asieh Hosseini

    2013-01-01

    Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

  15. The influence of pyridoxine in diabetic peripheral neuropathy.

    Science.gov (United States)

    Levin, E R; Hanscom, T A; Fisher, M; Lauvstad, W A; Lui, A; Ryan, A; Glockner, D; Levin, S R

    1981-01-01

    To determine the role of pyridoxine in the treatment of diabetic peripheral neuropathy, 18 symptomatic diabetic patients were treated with vitamin B6 or placebo in a double-blind controlled study. Only one patient had a low plasma pyridoxal phosphate level at the start of the study. After 4 mo of treatment with pyridoxine hydrochloride (50 mg three times daily) 6 of 9 pyridoxine-treated and 4 of 9 placebo-treated patients noted significant relief from their neuropathic symptoms. There was no difference between the two groups with regard to fasting plasma glucose, motor nerve conduction velocity, or ophthalmologic examination at the beginning or at the conclusion of the study. Our results suggest that vitamin B6 deficiency is not a factor in the etiology of diabetic peripheral neuropathy. Furthermore, treating diabetic peripheral neuropathy with high dose vitamin B6 or placebo results in a similar frequency of symptomatic improvement.

  16. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria.

    Directory of Open Access Journals (Sweden)

    Ioannis N Petropoulos

    Full Text Available Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS, vibration perception threshold (VPT, peroneal motor nerve conduction velocity (PMNCV, sural sensory nerve conduction velocity (SSNCV and in vivo corneal confocal microscopy (IVCCM], retinopathy (digital fundus photography and albuminuria status [albumin: creatinine ratio (ACR].53 patients with Type 1 diabetes with (n=37 and without retinopathy (n=16 were compared to control subjects (n=27. SSNCV, corneal nerve fibre (CNFD and branch (CNBD density and length (CNFL were reduced significantly (p<0.001 in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001 reduced in diabetic patients without microalbuminuria (n=39, compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.

  17. Effectiveness of combined alprostadil and pancreatic kininogenas in treating gerontal diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    张玉

    2013-01-01

    Objective To observe the clinical effectiveness of alprostadil combined with pancreatic kininogenas in the treatment of gerontal diabetic peripheral neuropathy.Methods Totally 90 gerontal patients with diabetic peripheral neuropathy were randomly divided into three

  18. Diagnostic accuracy of laser evoked potentials in diabetic neuropathy.

    Science.gov (United States)

    Di Stefano, G; La Cesa, S; Leone, C; Pepe, A; Galosi, E; Fiorelli, M; Valeriani, M; Lacerenza, M; Pergolini, M; Biasiotta, A; Cruccu, G; Truini, A

    2017-03-04

    Although the most widely agreed neurophysiological tool for investigating small fibre damage is laser evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological and skin biopsy study we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed-fibre polyneuropathy and assessed the sensitivity and specificity of LEPs in diabetic small-fibre neuropathy.From 288 LEP recordings from the face, hand and foot in 73 healthy subjects we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fibre diabetic neuropathy and 25 patients with possible small-fibre diabetic neuropathy. In the 100 patients with mixed-fibre neuropathy we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small-fibre neuropathy, using the skin biopsy for assessing the intraepidermal nerve fibre density, as a reference standard, we calculated LEP sensitivity and specificity.In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small-fibre neuropathy.Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small-fibre neuropathy.

  19. Role of A3 adenosine receptor in diabetic neuropathy.

    Science.gov (United States)

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  20. Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab).

    Science.gov (United States)

    Biessels, G J; Bril, V; Calcutt, N A; Cameron, N E; Cotter, M A; Dobrowsky, R; Feldman, E L; Fernyhough, P; Jakobsen, J; Malik, R A; Mizisin, A P; Oates, P J; Obrosova, I G; Pop-Busui, R; Russell, J W; Sima, A A; Stevens, M J; Schmidt, R E; Tesfaye, S; Veves, A; Vinik, A I; Wright, D E; Yagihashi, S; Yorek, M A; Ziegler, D; Zochodne, D W

    2014-06-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.

  1. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (Pmotor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (Pdevelopment of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  2. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments.

    Science.gov (United States)

    Tesfaye, Solomon; Boulton, Andrew J M; Dyck, Peter J; Freeman, Roy; Horowitz, Michael; Kempler, Peter; Lauria, Giuseppe; Malik, Rayaz A; Spallone, Vincenza; Vinik, Aaron; Bernardi, Luciano; Valensi, Paul

    2010-10-01

    Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

  3. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments

    DEFF Research Database (Denmark)

    Tesfaye, Solomon; Boulton, Andrew J M; Dyck, Peter J

    2010-01-01

    Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates...... on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs....

  4. Protection of Trigonelline on Experimental Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Ji-Yin Zhou

    2012-01-01

    Full Text Available The mechanisms leading to diabetic peripheral neuropathy are complex and there is no effective drug to treat it. As an active component of several traditional Chinese medicines, trigonelline has beneficial effects on diabetes with hyperlipidemia. The protective effects and the mechanism of trigonelline on diabetic peripheral neuropathy were evaluated in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Rats were divided into four groups at the end of week 2: control, diabetes, diabetes + trigonelline (40 mg/kg, and diabetes + sitagliptin (4 mg/kg. After 48-week treatment, technologies of nerve conduction, cold and hot immersion test, transmission electron microscopy, real-time PCR, and Western blotting were applied. Serum glucose, serum insulin, insulin sensitivity index, lipid parameters, body weight, sciatic nerve conduction velocity, nociception, glucagon-like peptide-1 receptor mRNA and protein, total and phosphorylated p38 mitogen-activated protein kinases protein expression, malonaldehyde content, and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with trigonelline. Slight micropathological changes existed in sciatic nerve of trigonelline-treated diabetic rats. These findings suggest that trigonelline has beneficial effects for diabetic peripheral neuropathy through glucagon-like peptide-1 receptor/p38 mitogen-activated protein kinases signaling pathway, nerve conduction velocity, antioxidant enzyme activity, improving micropathological changes of sciatic nerve and decreasing lipid peroxidation.

  5. Prevalence and Characteristics of Painful Diabetic Neuropathy in a Large Community-Based Diabetic Population in the U.K.

    OpenAIRE

    Abbott, Caroline A; Malik, Rayaz A; van Ross, Ernest R.E.; Kulkarni, Jai; Boulton, Andrew J.M.

    2011-01-01

    OBJECTIVE To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. RESEARCH DESIGN AND METHODS Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (...

  6. The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

    DEFF Research Database (Denmark)

    Hansen, C.S.; Jensen, T.M.; Jensen, J.S.

    2015-01-01

    AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...

  7. The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

    DEFF Research Database (Denmark)

    Hansen, C.S.; Jensen, T.M.; Jensen, J.S.

    2015-01-01

    AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...

  8. Assessment of sensory neuropathy in patients with diabetic foot problems

    Directory of Open Access Journals (Sweden)

    Aziz Nather

    2011-06-01

    Full Text Available Our aim of this study was to compare the accuracy of three different modalities for testing sensory neuropathy in diabetic patients with and without diabetic foot problems. The three devices used included the pin-prick testing using the Neurotip® (PPT, the Semmes–Weinstein 5.07/10 g monofilament testing (SWMT, and the rapid-current perception threshold (R-CPT measurements using the Neurometer® testing. Our study population consisted of 54 patients (108 feet with diabetic foot problems treated at the National University Hospital in Singapore by our multi-disciplinary diabetic foot care team. Our results showed no difference in sensory neuropathy detected by PPT and 5.07/10 g SWMT in both the pathological and normal foot. In the pathological foot, there was significant increase in sensory neuropathy detected by the Neurometer® device at both the big toe and ankle sites as compared to PPT and 5.07/10 g SWMT. In the normal foot, there was a significant increase in sensory neuropathy detected by the Neurometer® device at the big toe site only as compared to PPT and 5.07/10 g SWMT. Finally, the Neurometer® measurements detected a statistically higher proportion of feet with sensory neuropathy as compared to detection by the PPT or 5.07/10 g SWMT.

  9. Recent advances in exploring the genetic susceptibility to diabetic neuropathy.

    Science.gov (United States)

    Politi, Cristina; Ciccacci, Cinzia; D'Amato, Cinzia; Novelli, Giuseppe; Borgiani, Paola; Spallone, Vincenza

    2016-10-01

    Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis. This review is aimed at describing major data from the available literature regarding genetic susceptibility to diabetic neuropathies. It provides an overview of the genes reported as associated with the development or progression of these complications, i.e. ACE, MTHFR, GST, GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A, MIR128A. The identification of genetic susceptibility can help in both expanding the comprehension of the pathogenetic mechanisms of diabetic nerve damage and identifying biomarkers of risk prediction and response to therapeutic intervention.

  10. Blood pressure regulation in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1985-01-01

    experimental situations insufficient contraction of resistance vessels has been demonstrated. The vasoconstrictor defects demonstrated are of a magnitude sufficient to account for the prevailing hypotension. Furthermore, during exercise cardiac output is low in patients with autonomic neuropathy, a finding...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

  11. Hypoxic neuropathy versus diabetic neuropathy : an electrophysiological study in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Hendriksen, P.H.; Oey, P.L.; Wieneke, G.H.; Huffelen, A.C. van

    1992-01-01

    In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypo

  12. Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Astrup, Anne Sofie; Tarnow, Lise; Rossing, Peter

    2006-01-01

    Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy....

  13. Diabetic peripheral neuropathy: should a chaperone accompany our therapeutic approach?

    Science.gov (United States)

    Farmer, Kevin L; Li, Chengyuan; Dobrowsky, Rick T

    2012-10-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with axonal atrophy, demyelination, blunted regenerative potential, and loss of peripheral nerve fibers. The development and progression of DPN is due in large part to hyperglycemia but is also affected by insulin deficiency and dyslipidemia. Although numerous biochemical mechanisms contribute to DPN, increased oxidative/nitrosative stress and mitochondrial dysfunction seem intimately associated with nerve dysfunction and diminished regenerative capacity. Despite advances in understanding the etiology of DPN, few approved therapies exist for the pharmacological management of painful or insensate DPN. Therefore, identifying novel therapeutic strategies remains paramount. Because DPN does not develop with either temporal or biochemical uniformity, its therapeutic management may benefit from a multifaceted approach that inhibits pathogenic mechanisms, manages inflammation, and increases cytoprotective responses. Finally, exercise has long been recognized as a part of the therapeutic management of diabetes, and exercise can delay and/or prevent the development of painful DPN. This review presents an overview of existing therapies that target both causal and symptomatic features of DPN and discusses the role of up-regulating cytoprotective pathways via modulating molecular chaperones. Overall, it may be unrealistic to expect that a single pharmacologic entity will suffice to ameliorate the multiple symptoms of human DPN. Thus, combinatorial therapies that target causal mechanisms and enhance endogenous reparative capacity may enhance nerve function and improve regeneration in DPN if they converge to decrease oxidative stress, improve mitochondrial bioenergetics, and increase response to trophic factors.

  14. Protective effect of Jiaweibugan decoction against diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Yu Wang; Zeqi Chen; Renqun Ye; Yulei He; Yuhong Li; Xinjian Qiu

    2013-01-01

    Oxygen free radical damage is regarded as a direct or indirect common pathway associated with diabetic neuropathy and is the main cause of complications in peripheral neuropathies. We speculate that Jiaweibugan decoction has a significant effect in treating diabetic peripheral neuropathy through an anti-oxidative stress pathway. In this study, a diabetic rat model was established by intraperitoneal injection of streptozotocin. Rats were treated with Jiaweibugan decoction via intragastric administration. The levels of malondialdehyde and glutathione, which are indirect indexes of oxidative stress, in serum were determined using a colorimetric method. The expression levels of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase, which are oxidative stress associated factors, in the dorsal root ganglion of spinal S4–6 segments were evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results showed that, Jiaweibugan decoction significantly ameliorated motor nerve conduction velocity in diabetic rats, effectively decreased malondialdehyde levels in serum and the expression of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase mRNA in the dorsal root ganglion, and increased glutathione levels in serum. Therefore, our experimental findings indicate that Jiaweibugan decoction plays an anti-oxidative stress role in the diabetic peripheral neuropathy process, which has a protective effect on peripheral nerve injury.

  15. Angiogenin gene polymorphism: A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population.

    Science.gov (United States)

    Wang, Hongli; Fan, Dongsheng; Zhang, Yingshuang

    2013-12-25

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy patients) and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  16. Mexiletine for treatment of chronic painful diabetic neuropathy

    DEFF Research Database (Denmark)

    Dejgard, A; Kastrup, J; Petersen, P

    1988-01-01

    Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment...

  17. Oxidative stress and diabetic neuropathy : pathophysiotogical mechanisms and treatment perspectives

    NARCIS (Netherlands)

    2002-01-01

    Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiolog

  18. Cough reflex sensitivity in adolescents with diabetic autonomic neuropathy

    OpenAIRE

    2009-01-01

    Abstract Objective Diabetic autonomic neuropathy (DAN) is one of the chronic complications of diabetes mellitus which can involve one or more organ systems. DAN without apparent symptoms is more often in childhood and adolescence. While heart rate variability (HRV) and Ewing's battery of cardiovascular tests are regarded as a gold standard for the diagnosis of DAN, the examination of cough reflex sensitivity (CRS) is another possibility. The aim of this study was to compare HRV and CRS in chi...

  19. Insulin influenced expression of myelin proteins in diabetic peripheral neuropathy.

    Science.gov (United States)

    Rachana, Kuruvanthe S; Manu, Mallahalli S; Advirao, Gopal M

    2016-08-26

    Diabetic peripheral neuropathy (DPN) is one of the downstream complications of diabetes. This complication is caused by the deficiency of insulin action and subsequent hyperglycemia, but the details of their pathogenesis remain unclear. Hence, it is of critical importance to understand how such hormonal variation affects the expression of myelin proteins such as myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in the peripheral nerve. An earlier report from our lab has demonstrated the expression of insulin receptors (IR) in Schwann cells (SCs) of sciatic nerve. To assess the neurotrophic role of insulin in diabetic neuropathy, we studied the expression of these myelin proteins under control, DPN and insulin treated DPN subjects at developmental stages. Further, the expression of these myelin proteins was correlated with the expression of insulin receptor. Expression of myelin proteins was significantly reduced in the diabetic model compared to normal, and upregulated in insulin treated diabetic rats. Similarly, an in vitro study was also carried out in SCs grown at high glucose and insulin treated conditions. The expression pattern of myelin proteins in SCs was comparable to that of in vivo samples. In addition, quantitative study of myelin genes by real time PCR has also showed the significant expression pattern change in the insulin treated and non-treated DPN subjects. Taken together, these results corroborate the critical importance of insulin as a neurotrophic factor in demyelinized neurons in diabetic neuropathy.

  20. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

    Science.gov (United States)

    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (pdiabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (pdiabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

  1. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  2. Diabetic neuropathy in the gut: pathogenesis and diagnosis.

    Science.gov (United States)

    Azpiroz, Fernando; Malagelada, Carolina

    2016-03-01

    The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived. However, under certain circumstances, digestive stimuli may activate sensory afferents and give rise to conscious sensations. Both reflex and sensory signals are modulated by a balance of excitatory and inhibitory mechanisms. Patients with diabetes may develop a neuropathy affecting the control of gastric and/or intestinal motor function and the sensory innervation as well. During fasting the stomach is contracted and relaxes to accommodate a meal. After ingestion the stomach progressively recontracts and this contraction gently produces gastric emptying. Impairment of excitatory pathways affects the contraction of the stomach, which may result in delayed gastric emptying and vomiting of retained food. Conversely, alteration of the inhibitory neural pathways results in impaired relaxation of the stomach in response to a meal; in this case increased wall tension may produce early satiation, fullness and nausea. Diabetic neuropathy may distort the control of intestinal motility, which can lead to diverse symptoms such as diarrhoea, constipation, intestinal distension and abdominal pain. Neuropathy in diabetes may also affect the sensory nerves of the gut, and depending on which pathways are involved, perception may be increased or reduced. In summary, in patients with diabetic neuropathy, disorders of gut motor function are associated with sensory abnormalities, and the combination of impaired pathways determines the clinical consequences. This review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Hans Törnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the

  3. The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

    Science.gov (United States)

    Bilir, Bulent; Tulubas, Feti; Bilir, Betul Ekiz; Atile, Neslihan Soysal; Kara, Sonat Pinar; Yildirim, Tulay; Gumustas, Seyit Ali; Topcu, Birol; Kaymaz, Ozlem; Aydin, Murat

    2016-07-01

    [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

  4. Symptom scoring systems to diagnose distal polyneuropathy in diabetes : the Diabetic Neuropathy Symptom score

    NARCIS (Netherlands)

    Meijer, J.W.G.; Smit, A.J.; van Sonderen, E.; Groothoff, J.W.; Eisma, W.H.; Links, T.P.

    2002-01-01

    AIMS: To provide one of the diagnostic categories for distal diabetic polyneuro-pathy,several symptom scoring systems are available, which are often extensive andlack in validation. We validated a new four-item Diabetic Neuropathy Symptom (DNS) scorefor diagnosing distal diabetic polyneuropathy. MET

  5. Mitochondrial transcription factor A regulation of mitochondrial degeneration in experimental diabetic neuropathy.

    Science.gov (United States)

    Chandrasekaran, Krish; Anjaneyulu, Muragundla; Inoue, Tatsuya; Choi, Joungil; Sagi, Avinash Rao; Chen, Chen; Ide, Tamomi; Russell, James W

    2015-07-15

    Oxidative stress-induced mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in peripheral neurons is considered to be important in the development of diabetic neuropathy. Mitochondrial transcription factor A (TFAM) wraps mtDNA and promotes mtDNA replication and transcription. We studied whether overexpression of TFAM reverses experimental peripheral diabetic neuropathy using TFAM transgenic mice (TFAM Tg) that express human TFAM (hTFAM). Levels of mouse mtDNA and the total TFAM (mouse TFAM + hTFAM) in the dorsal root ganglion (DRG) increased by approximately twofold in the TFAM Tg mice compared with control (WT) mice. WT and TFAM Tg mice were made diabetic by the administration of streptozotocin. Neuropathy end points were motor and sensory nerve conduction velocities, mechanical allodynia, thermal nociception, and intraepidermal nerve fiber density (IENFD). In the DRG neurons, mtDNA copy number and damage to mtDNA were quantified by qPCR, and TFAM levels were measured by Western blot. Mice with 16-wk duration of diabetes developed motor and sensory nerve conduction deficits, behavioral deficits, and intraepidermal nerve fiber loss. All of these changes were mostly prevented in diabetic TFAM Tg mice and were independent of changes in blood parameters. Mice with 16 wk of diabetes had a 40% decrease in mtDNA copy number compared with nondiabetic mice (P diabetic TFAM Tg mice reached the same level as that of WT nondiabetic mice. In comparison, there was upregulation of mtDNA and TFAM in 6-wk diabetic mice, suggesting that TFAM activation could be a therapeutic strategy to treat peripheral neuropathy.

  6. Sexual Dysfunction in Patients with Diabetes Mellitus: The Role of a "Central" Neuropathy.

    Science.gov (United States)

    Nofzinger

    1997-01-01

    Sexual behavior involves the complex integration of higher intellectual function, such as associative memory and the experience of drives and motivations, with basic instinctual or reflexive physiological responses coordinated at the spinal level. Previous research in diabetic sexual dysfunction has largely focused on diabetic male erectile dysfunction, emphasizing a peripheral vasculopathy or neuropathy as etiologic factors, although ignoring the more complex neuropsychiatric components of sexual behavior. Following a review of the basic physiology of sexual behavior and evidence in support of a peripheral vasculopathy and/or a peripheral autonomic neuropathy in the cause of diabetic sexual dysfunction, emphasis will then shift to the role of a "central" neuropathy as a contributing component of diabetic sexual dysfunction. Evidence in support of such a view will come from a variety of studies, ranging from basic neuroscience research on forebrain mechanisms of sexual function to the functional brain imaging of human rapid eye movement (REM) sleep, a brain state known to be associated with the periodic occurrence of penile tumescence. An integrative perspective of this research will identify major candidate structures within the brain that may be dysfunctional in diabetic patients and may contribute to the profound sexual dysfunction that characterizes this condition. Major findings as well as deficits in our understanding of the effects of diabetes on female sexual dysfunction will also be highlighted, followed by suggestions for future research in this largely understudied area.

  7. STUDY OF DIABETES PATIENTS WITH PERIPHERAL NEUROPATHY IN BRIMS TEACHING HOSPITAL, BIDAR

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2014-08-01

    Full Text Available OBJECTIVE: Peripheral neuropathy is a common complication of diabetes. The Prevalence of peripheral neuropathy among diabetic patients on the basis of loss of vibration sensation had been studied. METHODOLOGY: Detailed clinical history of each patient including age, gender, duration of diabetes, foot ulcer and biothesiometry was recorded in 91 diabetic patients between 20 to 80 age. It was observed that all patients under years of age (n=8 felt vibration below 15 volts (no risk zone; 77% (24 out of 31 of the patients in the age group 30-39 years were in the no risk zone, and 23% (n=7 had mild peripheral neuropathy. Sixty per cent of the patients between 40 and 50 years (n=44 were in the no risk zone, while 32% (n=24 had mild peripheral neuropathy, 5% (n=4 had moderate neuropathy and 3% (n=2 have severe neuropathy. RESULTS: Amongst patients above 50 years of age, 31% (n=31 were no risk zoen, 34% (n=34 had mild peripheral neuropathy, 22% (n=20 had moderate peripheral neuropathy and 13% (n=13 had severe peripheral neuropathy. Of the patients with diabetes for less than 5 years, 58% had no neuropathy and only 3% had severe neuropathy. Of the patients with diabetes for 5 to 15 years, 50% had no neuropathy, 30% had mild and 10% had severe peripheral neuropathy. When patients with diabetes for over 15 years were studied only 6% had no neuropathy and 19% had severe peripheral neuropathy. CONCLUSION: The study reestablishes that the severity of peripheral neuropathy increases with age and vibration perception decreases progressively with increased duration of diabetes. Vibration perception threshold testing helps to identify the high risk the high subjects who require special counseling and education to protect their feet

  8. [Dyschromatopsia: manifestation or epiphenomenon in the course of diabetic neuropathy].

    Science.gov (United States)

    Doucet, J; Chassagne, P; Trivalle, C; Ozenne, G; Retout, A; Parain, D; Bercoff, E; Courtois, H; Schrub, J C

    1994-01-01

    We performed a study in 92 diabetic patients (76 Type 1 and 16 Type 2) without retinopathy to determine the relation between diabetic dyschromatopsia and neuropathy, which has been evoked in previous studies. Color vision was explored with Lanthony's desaturated D 15 panel. Peripheral nervous function was explored with an electrophysiological score which has been beforehand validated. Moreover evoked visual potentials were performed in 38 diabetic subjects in order to determine whether dyschromatopsia was related to an impairment of central optic pathways. Fifty-one among the 92 diabetic subjects had a blue-yellow dyschromatopsia. Among the recorded parameters, only peripheral nervous impairment was significantly more frequent in the group with dyschromatopsia than in the group without. Ten among 38 diabetics had impairment of the evoked visual potentials. Frequency of alteration of evoked visual potentials was not different between the group with and the group without dyschromatopsia. Our results confirm the relationship between dyschromatopsia and the alteration of the nervous function in diabetic subjects. In return, lack of significant modification of evoked visual potentials among diabetic patients with dyschromatopsia and the blue-yellow axis of dyschromatopsia are in opposition with a direct neurological origin of dyschromatopsia. We therefore evoke a common process in the beginning of the diabetic dyschromatopsia and of peripheral neuropathy.

  9. Plasma osteoprotegerin concentrations in peripheral sensory neuropathy in Type 1 and Type 2 diabetic patients

    DEFF Research Database (Denmark)

    Nybo, M; Poulsen, M K; Grauslund, J

    2010-01-01

    Osteoprotegerin (OPG) has been linked to different diabetes complications, including cardiovascular disease, and new findings have indicated a specific role in diabetic peripheral neuropathy, but the exact mechanism is unknown. To investigate a possible association between OPG and diabetic periph...

  10. Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

    Institute of Scientific and Technical Information of China (English)

    黄一宁; 贾志荣; 石昕; 孙相如

    2004-01-01

    Background Diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy.Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (P0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.

  11. Pruritus induced self injury behavior: an overlooked risk factor for amputation in diabetic neuropathy?

    Science.gov (United States)

    Dorfman, David; George, Mary Catherine; Tamler, Ronald; Lushing, Julia; Nmashie, Alexandra; Simpson, David M

    2014-03-01

    Pruritus is a risk factor for self-injury behavior (SIB) in sensory polyneuropathies. Although diabetes patients have elevated risk for pruritus, there are no reports of SIB in diabetic neuropathy. We present the case of a diabetes patient with neuropathy, whose pruritus induced SIB, resulted in partial amputation of a toe.

  12. Clinical Research on Acupuncture Treatment of Diabetic Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    QIAN Wei-hua; QIAN Hong; WU Tong; BEI Yan-hui; LI Lan; QING Liang-cai

    2004-01-01

    目的:探讨针刺治疗糖尿病周围神经病变的相关机理.方法:运用针刺疗法治疗糖尿病周围神经病变,并与口服钙离子拮抗剂加维生素疗法进行随机对照观察,同时作肌电图检测分析.结果:针刺治疗糖尿病周围神经病变可不同程度地改善病人的肢体麻木、疼痛和感觉异常等临床症状,肌电图结果提示神经运动传导速度和感觉传导速度也有明显改善.结论:针刺治疗糖尿病周围神经病变的临床疗效明显优于口服钙离子拮抗剂加维生素治疗.%Purpose: To investigate the mechanism of acupuncture treatment of diabetic peripheral neuropathy. Methods: Acupuncture therapy was used to treat diabetic peripheral neuropathy, and compared with oral calcium antagonist and vitamin therapy by random control observation.Electromyography was performed for analysis at the same time. Results: Acupuncture treatment alleviated symptoms such as extremity numbness, pain and paresthesia in varying degrees in diabetic patients with peripheral neuropathy. The results of electromyography showed a marked improvement in motor and sensory conduction velocities. Conclusion: It is indicated that acupuncture therapy is markedly superior to oral calcium antagonist and vitamin therapy in clinical effect on diabetic peripheral neuropathy, and electromyographic recovery.

  13. Effect of Large Dose Methylcobalamin on Diabetic Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The effects of large dose methylcobalamin injection on diabetic peripheral neuropathy in patients were observed to observe the subjective symptom of diabetic perpheral neuropathy (DPN) patients and detect the motor nerve conduction velocity (MCV) and sense nerve conduction velocity (SCV). Fifteen patients were received large dose methylcobalamin injection for two weeks as treatment group, another eleven patients were received muscular injection VitB1 100mg/ d, VitB12 500ug/ d for two weeks as control group. After 2 weeks treatment the subjective symptoms and signs were significantly improved with a total effective rate of 82.9% in the treatment group however the effective rate only has 52.0% in the control group. The result has obvious difference in statistics nerve MCV in median common peroneal nerve, SCV in median and superficial peroneal nerve were improved significantly in the treatment group and no such changes were observed in the control group. So, large dose methylcobalamin is an effective and safe agent for treatment of diabetic peripheral neuropathy.

  14. [Diabetic neuropathies: clinical sub-types, early detection and asking help from the specialist].

    Science.gov (United States)

    Kuntzer, Thierry; Ruiz, Juan

    2014-04-30

    In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of diabetic neuropathies are examined, and it is discussed why and how the general practionner has to perform a yearly examination. At the present time, some consensuses emerge to ask help from the specialist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

  15. [Diabetic neuropathies: clinical sub-types, early detection, and asking help from neurologist].

    Science.gov (United States)

    Kuntzer, T; Medlin, F; Burnand, B; Camain, J-Y

    2012-10-03

    In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of DPN and other diabetic neuropathies are examined, and it is discussed why and how the general practitioner has to perform a yearly examination. At the present time, some consensus emerge to ask help from neurologist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

  16. No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Krarup, T

    1982-01-01

    The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had...... no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity...

  17. Association between the level of serum vitamin D and peripheral neuropathy in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    张吉平

    2014-01-01

    Objective To evaluate the relationship between 25-(OH)vitamin D[25-(OH)D]level and peripheral neuropathy in patients with type 2 diabetes mellitus.Methods Eighty patients with type 2 diabetes mellitus were enrolled in this cross-sectional study,including 37 subjects with and 43 without diabetic neuropathy.Anthropometric data was collected and serum levels of 25-(OH)D,Hb A1C,blood lipid,and hepatic and renal functions were determined in all patients.Results Serum 25-(OH)D level was significantly lower in patients with diabetic neuropathy compared to those without neuropathy

  18. Alteration of foot temperature in diabetic neuropathy: is it another piece of puzzle?

    Science.gov (United States)

    Naicker, A S; Roohi, S A; Lee, C S; Chan, W H; Tay, L S; Din, X J; Eow, L H

    2006-02-01

    Poor glycaemic control and the duration of diabetes mellitus are known to accelerate development and progression of neuropathy. Diabetic co-morbidities: hypertension and hyperlipidaemia, have been postulated to associate with development of neuropathy. A diabetic foot with low temperature and frequent exposure to low temperature environment has recently been hypothesized to be at higher risk to develop early neuropathy. This cross-sectional study is undertaken to identify risk factors for diabetic neuropathy and the association between foot temperature and development of diabetic neuropathy by using simple clinical examination in the outpatient setting. From April 18, to April 30, 2005, universal sampling method was used to select 134 diabetic patients (type 1 or type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and family history of porphyria and hereditary sensorimotor neuropathy. The patient's duration of diabetes, glycaemic control status and the presence of co-morbids: hypertension and hyperlipidemia, were recorded. The temperature of the foot was measured by using thermo buddy. Of 134 patients representing Malaysian ethnic distribution with an equal number of males and females, 20.1% were in the age group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and educational groups respectively. Associations between diabetic neuropathy and glycaemic control (p = 0.018) and duration of diabetes (p development of diabetic neuropathy. Poor glycaemic control is significantly associated with diabetic neuropathy. Foot temperature alteration is merely an effect of autonomic neuropathy with a cold foot is attributed to co-existing peripheral arterial disease.

  19. Experiences in Treating Diabetic Peripheral Neuropathy with Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    WEI Zi-xiao

    2008-01-01

    @@ Diabetic peripheral neuropathy (DPN) is a common chronic complication in diabetic patients, closely correlated with the development of the disease and with poorly controlled glucose levels. The common clinical signs show paresthesia, mostly manifesting as multiple peripheral neuritis, such as having a chilly or causalgic feeling, anaesthesia, formication, and pain, etc. All the symptoms usually start from the four extremities. The abnormal sensations at the limbs manifest as hyperesthesia in the early stage; however, it will decrease or vanish in the later stages. Dyskinesia is not uncommon, seen as decreased tendon reflex or myoatrophy.

  20. Diabetic cachectic neuropathy: An uncommon neurological ...

    African Journals Online (AJOL)

    A 40-year-old female patient with diabetes of 12 years' duration, with poor drug ... of rapid progressive weight loss, burning sensations in the feet, abdominal swelling, ... Blood pressure measurements in the supine and standing positions were ...

  1. Ghrelin reverses experimental diabetic neuropathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  2. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy.

    Science.gov (United States)

    Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M

    2013-06-30

    Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN.

  3. Modeling diabetic sensory neuropathy in rats.

    Science.gov (United States)

    Calcutt, Nigel A

    2004-01-01

    The procedures to induce insulin-deficient diabetes in rats using streptozotocin are described along with a number of insulin treatment regimes that can be used to maintain these animals at different degrees of glycemia for periods of weeks to months. Streptozotocin-diabetic rats develop tactile allodynia, hyperalgesia following paw formalin injection and abnormal responses to thermal stimulation and the detailed methods used to evaluate these behavioral indices of abnormal sensory function are provided.

  4. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

    DEFF Research Database (Denmark)

    Feldman, Eva L; Nave, Klaus-Armin; Jensen, Troels Staehelin

    2017-01-01

    the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights......Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand...... gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our...

  5. Mechanisms of disease: Mitochondrial dysfunction in sensory neuropathy and other complications in diabetes.

    Science.gov (United States)

    Fernyhough, Paul; McGavock, Jonathan

    2014-01-01

    Diabetic neuropathy is a major complication of diabetes that involves the sensory and autonomic nervous systems and leads to significant morbidity and impact on quality of life of patients. Mitochondrial stress has been proposed as a major mediator of insulin sensitivity in skeletal muscle in type 2 diabetes and a trigger of diabetic complications such as nephropathy and cardiomyopathy in humans and animal models. Recent studies in the peripheral nervous system in type 1 and type 2 diabetic animal models suggest a role for mitochondrial dysfunction in neurodegeneration in diabetes. This chapter focuses on the nature of sensory nerve dysfunction in diabetes and presents these findings in the context of diabetes-induced nerve degeneration mediated by alterations in mitochondrial physiology. Diabetes-induced dysfunction in calcium homeostasis is discussed and causative associations with suboptimal mitochondrial physiology are developed. Comparisons are made with mitochondrial-dependent dysfunction in muscle and cardiac tissue in diabetes. It is clear that across a range of complications of diabetes mitochondrial physiology is impaired; in general, a reduction in respiratory chain capability is apparent. Where appropriate, we provide clinical evidence for mitochondrial dysfunction in the pathogenesis of complications in patients with diabetes. This abnormal activity may predispose mitochondria to generate elevated reactive oxygen species (ROS), although experimental proof remains lacking, but more importantly will deleteriously alter the bioenergetic status of neurons.

  6. [Autonomic neuropathy: a high risk complication for type 1 diabetes mellitus].

    Science.gov (United States)

    Foss-Freitas, Maria Cristina; Marques Junior, Wilson; Foss, Milton Cesar

    2008-03-01

    The pathological alteration of the nervous system in diabetic patients is extensive and frequently severe. The prevalence of the diabetic neuropathy reach high levels with the evolution of the diabetes, often showing frequencies higher than 50% in several groups of patients. The neurological lesion in this pathological situation is extensive in the diabetic patient, including widely the peripheral nervous system with its components sensory, motor and autonomic: with typical symptoms and in accordance with the pathogenesis of metabolic origin and/or microvascular disease. The autonomic nervous system is a main regulator of many systems in the human body. Then its lesion can promote significant alterations in the function of the cardiovascular, respiratory, gastrointestinal, urogenital system, that can be related to increased motality. This review anlyses the abnormalities related to lesion of the autonomic nervous system, particularly in type 1 diabetic patients, trying to characterize the risk of morbidity and mortality.

  7. Gallbladder ejection fraction using {sup 99m}Tc-DISIDA scan in diabetic autonomic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Jang; Kim, In Ju; Kim, Yong Ki; An, Jun Hyup [Pusan National Univ. Hospital, Pusan (Korea, Republic of); Yoo, Seok Dong [Dongkuk Univ. College of Medicine, Seoul (Korea, Republic of)

    2000-02-01

    We performed this study to evaluate the changes of gallbladder ejection fraction (GBEF) in diabetic patients with or without autonomic neuropathy. This study included 37 diabetic patients (25 women, 12 men, mean age 51 years) and 24 normal controls (10 women, 14 men, mean age 38 years). After intravenous injection of 185 MBq of {sup 99m}T{sub c}-DISIDA, serial anterior abdominal images were acquired before and after fatty meal. Regions of interest were applied on gallbladder and right hepatic lobe on 60 and 90 minute images to calculate GBEF. GBEF was significantly reduced in diabetes with autonomic neuropathy (43{+-}12.3%) and without autonomic neuropathy (57.5{+-}13.2%) compared with normal controls (68{+-}11.6%, p<0.05). And also, GBEF was significantly reduced in diabetes with autonomic neuropathy compared with diabetes without autonomic neuropathy (p<0.05). Fasting blood glucose level, age, sex, hemoglobin A1c, body mass index, serum lipid level were not different in these two diabetic patient groups (p>0.05). When 50.2% of GBEF was used as the criteria for diabetic autonomic neuropathy, the sensitivity and specificity were 80%, 76.5%, respectively. The area under receiver operating characteristic curve was 0.846. GBEF of diabetic patients with autonomic neuropathy was significantly reduced than that of diabetic patients without autonomic neuropathy.

  8. Cardiac autonomic neuropathy in patients with diabetes mellitus.

    Science.gov (United States)

    Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

    2014-02-15

    Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.

  9. Plasma adrenaline kinetics in type 1 (insulin-dependent) diabetic patients with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Dejgaard, A; Hilsted, J; Henriksen, Jens Henrik Sahl

    1989-01-01

    labelled adrenaline had been stopped was significantly prolonged in Type 1 diabetic patients with neuropathy compared to those without (after 20 min infusion 2.7 vs 2.2 min, p less than 0.02, after 75 min infusion 3.7 vs 2.9 min, p less than 0.05). The corresponding values for the mean sojourn time...... volume in Type 1 diabetic patients with neuropathy as compared to patients without neuropathy (estimated space of distribution 29 vs 20 l). Our results suggest that patients with diabetic neuropathy do not adjust the plasma adrenaline concentration to changes in adrenaline infusion rate as rapidly...... as those without neuropathy, i.e. the effect of an elevated adrenaline secretion rate may be prolonged in patients with diabetic autonomic neuropathy....

  10. Individual, Psycho-Social and Disease-Related Risk Factors in Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Isaac Rahimian-Boogar

    2012-09-01

    Full Text Available Background: Neuropathy is the mostly prevalent of complications and the major cause of amputation, pain and disability in patients with diabetes. The purpose of this study was to investigate the role of individual, psycho-social, and disease-related risk factors in neuropathy of type 2 diabetes patients.Materials and Methods: In this retrospective cross-sectional study, 271 patients with type 2 diabetes were selected by convenience sampling in diabetic outpatient clinics of Tehran University of Medical Sciences and the Iranian Diabetic Association. The data were collected by demographical and disease characteristics questionnaires and DASS-42, QOLS, DSMS, and DKS scales. Then, the data were analyzed by r binary logistic regression along with PASW software.Results: Socio-economic status, glycosylated hemoglobin, body mass index, diabetes self-management, depression, quality of life, diabetes knowledge, and diabetes duration were significantly able to differentiate diabetic patients with neuropathy from diabetic patients without neuropathy (p0.05. The total regression model explained that 95.2% of cases were classified correctly.Conclusion: Inappropriate socio-economic status, glycosylated hemoglobin over 9%, being overweight and obesity, poor diabetes self-management, clinical depression, low quality of life, poor diabetes knowledge, and longer diabetes duration contribute to the incidence of neuropathy in patients with type 2 diabetes and attention must be paid to them for neuropathy prevention.

  11. Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy

    OpenAIRE

    2012-01-01

    The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin ...

  12. Targeting the Diabetic Chaperome to Improve Peripheral Neuropathy.

    Science.gov (United States)

    Dobrowsky, Rick T

    2016-08-01

    The chaperome constitutes a broad family of molecular chaperones and co-chaperones that facilitate the folding, refolding, and degradation of the proteome. Heat shock protein 90 (Hsp90) promotes the folding of numerous oncoproteins to aid survival of malignant phenotypes, and small molecule inhibitors of the Hsp90 chaperone complex offer a viable approach to treat certain cancers. One therapeutic attribute of this approach is the selectivity of these molecules to target high affinity oncogenic Hsp90 complexes present in tumor cells, which are absent in nontransformed cells. This selectivity has given rise to the idea that disease may contribute to forming a stress chaperome that is functionally distinct in its ability to interact with small molecule Hsp90 modulators. Consistent with this premise, modulating Hsp90 improves clinically relevant endpoints of diabetic peripheral neuropathy but has little impact in nondiabetic nerve. The concept of targeting the "diabetic chaperome" to treat diabetes and its complications is discussed.

  13. [Interconnection of the angiopathy and neuropathy development mechanism at patients with type II pancreatic diabetes].

    Science.gov (United States)

    Saltykov, B B; Zinov'eva, O E

    2012-01-01

    In the article we summarized literature data, covered genesis of angiopathy and neuropathy at patients with type II diabetes. In the genesis of disease different metabolic, immune, hypoxic, genetic and others factors, caused affection of arteries, microcirculation and the peripheral nervous system, play an important role. Increasing changes of the great and minute vessels are interconnected with diabetic neuropathy

  14. [Autonomic dysfunction syndrome and diabetic cardiac autonomic neuropathy in children with diabetes mellitus type I. The correction method].

    Science.gov (United States)

    Manukian, V Iu; Bolotova, N V; Aver'ianov, A P; Filina, N Iu; Raĭgorodskiĭ, Iu M

    2011-01-01

    We assessed the state of the autonomic nervous system in 90 children with diabetes mellitus type I. The autonomic dysfunction syndrome was found in 58,9% and diabetic cardiac autonomic neuropathy in 28,9% of patients. We revealed the high risk of the development of diabetic cardiac autonomic neuropathy in children with diabetes mellitus type I in the presence of the autonomic dysfunction syndrome. It has been shown that the early treatment of functional disturbances of the autonomic nervous system using transcranial magnetic stimulation is necessary to prevent the manifestation of diabetic cardiac autonomic neuropathy.

  15. Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

    2016-03-01

    Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

  16. Channelopathies, painful neuropathy, and diabetes: which way does the causal arrow point?

    Science.gov (United States)

    Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G

    2014-10-01

    Diabetes mellitus, a major global health problem, is commonly associated with painful peripheral neuropathy, which can substantially erode quality of life. Despite its clinical importance, the pathophysiology of painful diabetic neuropathy is incompletely understood. It has traditionally been thought that diabetes may cause neuropathy in patients with appropriate genetic makeup. Here, we propose a hypothesis whereby painful neuropathy is not a complication of diabetes, but rather occurs as a result of mutations that, in parallel, confer vulnerability to injury in pancreatic β cells and pain-signaling dorsal root ganglion (DRG) neurons. We suggest that mutations of sodium channel NaV1.7, which is present in both cell types, may increase susceptibility for development of diabetes via β cell injury and produce painful neuropathy via a distinct effect on DRG neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients

    Institute of Scientific and Technical Information of China (English)

    Ahmad Marzban; Javad Kiani; Mehrdad Hajilooi; Hamzeh Rezaei; Zohreh Kahramfar; Ghasem Solgi

    2016-01-01

    The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. hTis study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 andP = 0.05 respectively). Also, patients with severe neurop-athy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our ifndings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

  18. Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged diabetes mellitus: The Dogo Study.

    Science.gov (United States)

    Furukawa, S; Sakai, T; Niiya, T; Miyaoka, H; Miyake, T; Yamamoto, S; Maruyama, K; Ueda, T; Senba, H; Todo, Y; Torisu, M; Minami, H; Onji, M; Tanigawa, T; Matsuura, B; Hiasa, Y; Miyake, Y

    2017-01-01

    Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

  19. An option for painful diabetic neuropathy with simultaneous AND#8216;antioxidativeAND#8217; and AND#8216;anestheticAND#8217; properties: topical Citrullus colocynthis

    OpenAIRE

    2014-01-01

    Diabetic neuropathy is probably the most common complication of diabetes mellitus. Secondary preventive measures for diabetic neuropathy with delaying, stopping or even reversing progressive course of neuropathy, pain control and prevention of ulceration can play important role in diabetic patients care. Oxidative stress plays an important role in pathogenesis of diabetic neuropathy. Treatments for diabetic neuropathy have been mainly focused on two purposes, pain control and repair of nerve ...

  20. Cough reflex sensitivity in adolescents with diabetic autonomic neuropathy

    Directory of Open Access Journals (Sweden)

    Ciljakova M

    2009-12-01

    Full Text Available Abstract Objective Diabetic autonomic neuropathy (DAN is one of the chronic complications of diabetes mellitus which can involve one or more organ systems. DAN without apparent symptoms is more often in childhood and adolescence. While heart rate variability (HRV and Ewing's battery of cardiovascular tests are regarded as a gold standard for the diagnosis of DAN, the examination of cough reflex sensitivity (CRS is another possibility. The aim of this study was to compare HRV and CRS in children with diabetes mellitus. Materials and methods Sixty one patients (37 girls, 24 boys aged 15-19 suffering from diabetes mellitus type 1 completed the study. Based on HRV, patients were divided into 2 groups - with DAN (n = 25 and without DAN (n = 32, 4 patients were excluded because of ambiguous results. CRS was studied in each patient by inhalation of gradually increasing concentration of capsaicin. Results Subjects with DAN required a significantly higher concentration of capsaicin needed to evoke 2 coughs (median 625 μmol/l, IQR 68.4-625.0 μmol/l vs. median 29.3 μmol/l, IQR 9.8-156.3 μmol/l, P Conclusion Diabetes mellitus lowers the cough response. Cough reflex sensitivity appears to be another sensitive method for the evaluation of DAN in diabetes.

  1. Burning through the pain: treatments for diabetic neuropathy.

    Science.gov (United States)

    Javed, S; Alam, U; Malik, R A

    2015-12-01

    The rise in the global burden of diabetes is spurring an increase in the prevalence of its complications. Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, with multiple clinical manifestations. The most common is a symmetrical length-dependent dysfunction and damage of peripheral nerves. The management of DPN rests on three tenets: intensive glycaemic control, even though the evidence of benefit is questionable in people with type 2 diabetes; pathogenetic therapies; and symptomatic treatment. A number of pathogenetic treatments have been evaluated in phase III clinical trials, including α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage) and aldose-reductase inhibitors (reduce flux through the polyol pathway), protein kinase C inhibitors (prevent hyperglycaemia-induced activation of protein kinase C), nerve growth factors (stimulate nerve regeneration) and Actovegin® (improves tissue glucose and oxygen uptake). However, none have gained US Food and Drug Administration or European Medicines Agency (EMA) approval, questioning the validity of current trial designs and the endpoints deployed to define efficacy. For painful diabetic neuropathy, clinical guidelines recommend: atypical analgesics for pain relief, including duloxetine and amitriptyline; the γ-aminobutyric acid analogues gabapentin and pregabalin; opioids, including Tapentadol; and topical agents such as lidocaine and capsaicin. No single effective treatment exists for painful DPN, highlighting a growing need for studies to evaluate more potent and targeted drugs, as well as combinations. A number of novel potential candidates, including erythropoietin analogues and angiotensin II type 2 receptor anatagonists are currently being evaluated in phase II clinical trials.

  2. Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

    DEFF Research Database (Denmark)

    Brock, Christina; Søfteland, Eirik; Gunterberg, Veronica

    2013-01-01

    OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal...... symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid...... autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation....

  3. Inflammation as a Therapeutic Target for Diabetic Neuropathies.

    Science.gov (United States)

    Pop-Busui, Rodica; Ang, Lynn; Holmes, Crystal; Gallagher, Katherine; Feldman, Eva L

    2016-03-01

    Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs.

  4. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences.

    Science.gov (United States)

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28(th) day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy.

  5. Relationships between presynaptic inhibition and static postural sway in subjects with and without diabetic neuropathy.

    Science.gov (United States)

    Chun, Jihyun; Hong, Junggi

    2015-09-01

    [Purpose] Diabetic peripheral neuropathy can often lead to balance impairment. The spinal reflex is a mechanism that is reportedly important for balance, but it has not been investigated in diabetic peripheral neuropathy patients. Moreover, inhibitory or facilitatory behavior of the spinal reflex-known as presynaptic inhibition-is essential for controlling postural sway. The purpose of this study was to compare the differences in as presynaptic inhibition and balance in subjects with and without diabetic peripheral neuropathy to determine the influence of presynaptic inhibition on balance in diabetic peripheral neuropathy patients. [Subjects and Methods] Presynaptic inhibition and postural sway were tested in eight patients (mean age, 58±6 years) and eight normal subjects (mean age, 59±7 years). The mean percent difference in conditioned reflex amplitude relative to the unconditioned reflex amplitude was assessed to calculate as presynaptic inhibition. The single-leg balance index was measured using a computerized balance-measuring device. [Results] The diabetic peripheral neuropathy group showed lower presynaptic inhibition (47±30% vs. 75±22%) and decreased balance (0.65±0.24 vs. 0.38±0.06) as compared with the normal group. No significant correlation was found between as presynaptic inhibition and balance score (R=0.37). [Conclusion] Although the decreased as presynaptic inhibition observed in diabetic peripheral neuropathy patients may suggest central nervous system involvement, further research is necessary to explore the role of presynaptic inhibition in decreased balance in diabetic peripheral neuropathy patients.

  6. Effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies.

    Science.gov (United States)

    Song, Chang Ho; Petrofsky, Jerrold S; Lee, Seung Won; Lee, Kyoung Jin; Yim, Jong Eun

    2011-08-01

    Diabetes is the most common cause of peripheral neuropathies. No definitive treatment for diabetic neuropathies has been reported, and very few studies have been published on the role of exercise in reducing either the symptoms or incidence of diabetic neuropathies. This study assessed the effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies. Thirty-eight patients with diabetes having peripheral neuropathies were enrolled, randomized, and subdivided in two groups: an experimental group of 19 participants with diabetes (72.9 ± 5.6 years old) and a control group of 19 participants with diabetes (73.2 ± 5.4 years old). Both groups received health education on diabetes for 50 min/week for 8 weeks. The experimental group practiced an additional balance exercise program for 60 min, two times a week. The exercise training was performed two times per week for 8 weeks. Results were evaluated by both static and dynamic balance and trunk proprioception. Postural sway significantly decreased (P < 0.05), the one-leg stance test significantly increased (P < 0.05), and dynamic balance from the Berg Balance Scale, Functional Reach Test, Timed Up and Go test, and 10-m walking time improved significantly after balance exercise (P < 0.05). Trunk repositioning errors also decreased with training (P < 0.05). The balance exercise program improved balance and trunk proprioception. These results suggested that a balance exercise is suitable for individuals with diabetic neuropathy.

  7. Evaluation of Effect of Nishamalaki on STZ and HFHF Diet Induced Diabetic Neuropathy in Wistar Rats.

    Science.gov (United States)

    Dawane, Jayshree Shriram; Pandit, Vijaya Anil; Bhosale, Madhura Shirish Kumar; Khatavkar, Pallawi Shashank

    2016-10-01

    Diabetic neuropathy is one of the most common complications affecting 50% of diabetic patients. Neuropathic pain is the most difficult types of pain to treat. There is no specific treatment for neuropathy. Nishamalaki (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes Mellitus (DM). So, efforts were made to test whether NA is useful in prevention of diabetic neuropathy. To evaluate the effect of NA on diabetic neuropathy in type 2 diabetic wistar rats. Group I (Control) vehicle treated consists of 6 rats. Diabetes induced in 36 wistar rats with Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High Fructose diet. After confirmation of development of diabetes; rats divided into six groups (n=6). Group II - VII Diabetic Control, NA low dose, NA High dose, Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid profile at the end. Eddy's hot plate and tail immersion test performed to assess thermal hyperalgesia and cold allodynia. Walking function test performed to assess motor function. Diabetic rats exhibited significant (pNishamalaki improved lipid profile. Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively prevented the development of diabetic neuropathy.

  8. [Metabolic and nutritional neuropathies: update in diabetes, vitamin B12 and copper deficiency].

    Science.gov (United States)

    Franques, J; Gazzola, S

    2013-12-01

    Metabolic and deficiency neuropathies retain a growing interest because of their important prevalence. The dismemberment of diabetic neuropathies is proceeded, letting distinct pathophysiological mechanisms appear. So, even if glycaemic control remains determining for preventing the neuropathy associated with type 1 diabetes, it seems to have a restricted role with type 2 diabetes in which other metabolic factors are involved. The diagnosis of neuropathy due to B12 vitamin deficiency remains a real challenge for the clinician. Indeed, positive and negative predictive values of serum B12 and metabolites assay are weak, only a good therapeutic response allows a reliable diagnostic. It is so recommended to know the clinical and contextual particularities of this etiology in order to not delay the vitamin substitution, determining for the functional outcome. Finally, copper deficiency remains an unknown cause of neuropathy which is suitable to raise in case of malabsorption but also and especially in case of abuse of dental adhesive rich in zinc.

  9. Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dongye; Zhang, Xiang; Lu, Liejing; Li, Haojiang; Zhang, Fang; Chen, Yueyao; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

    2014-09-10

    To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)

  10. Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Jianguo Cheng

    2012-01-01

    Full Text Available The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic blocks over a 26-month period provided sustained pain relief in his legs. Additional thoracic paravertebral blocks further provided control of the pain in the trunk which can occasionally be seen in severe diabetic neuropathy cases, consequent to extensive involvement of the intercostal nerves. These blocks provided sustained and significant pain relief and improvement of quality of life over a period of more than two years. We thus provided the first clinical evidence supporting the notion that sympathetic nervous system plays a critical role in painful diabetic neuropathy and sympathetic blocks can be an effective management modality of painful diabetic neuropathy. We concluded that the sympathetic nervous system is a valuable therapeutic target of pharmacological and interventional modalities of treatments in painful diabetic neuropathy patients.

  11. Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic.

    Science.gov (United States)

    Zhou, J Y; Zhang, Z; Qian, G S

    2016-01-01

    As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.

  12. Is the C677T polymorphism in methylenetetrahydrofolate reductase gene or plasma homocysteine a risk factor for diabetic peripheral neuropathy in Chinese individuals?

    Science.gov (United States)

    Wang, Hongli; Fan, Dongsheng; Hong, Tianpei

    2012-10-25

    The present study enrolled 251 diabetic patients, including 101 with neuropathy and 150 without neuropathy. Of the 150 patients, 100 had no complications, such as retinopathy, nephropathy, or neuropathy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants. Plasma homocysteine levels were also measured. Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy (P diabetic peripheral neuropathy compared with patients without diabetic complications. Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels. In conclusion, hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes. The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.

  13. Quantitative measurement of sympathetic neuropathy in patients with diabetes mellitus.

    Science.gov (United States)

    Nasimi, S G; Mearns, A J; Harness, J B; Heath, I

    1991-05-01

    Vasoconstriction occurs in the skin capillary blood flow of the healthy subject when posture changes from supine to standing. Using frequency analysis of the optical photoplethysmograph signal, a statistically significant difference (P less than 0.01) may be demonstrated between supine and standing positions in the lower frequency band (0.01-0.5 Hz) in the foot of normal subjects. This allowed us to develop a simple index: sympathetic power band change (SPBC). Patients with diabetes mellitus often suffer from degeneration in the sympathetic nervous system. This impairs the normal vasoconstrictor response to standing. We have applied the SPBC 'blind' to a group of diabetic patients. Such patients may be divided into three groups according to their SPBC indices: normals with SPBC greater than 2.6 (group A), intermediates with 2.6 greater than or equal to SPBC greater than or equal to 0.26 (group B) and poor with SPBC less than 0.26 (group C). All patients with retinopathy were in group C and five out of the six patients with electrophysiologically confirmed peripheral neuropathy were in group C. Frequency analysis of the photoplethysmograph signal has produced an index of sympathetic tone change when subjects move from supine to standing position. The application of this index to patients with diabetes mellitus shows some patients to have sympathetic vascular tone failure.

  14. Screening for diabetic cardiac autonomic neuropathy using a new handheld device

    DEFF Research Database (Denmark)

    Gulichsen, Elisabeth; Fleischer, Jesper; Ejskjaer, Niels

    2012-01-01

    Cardiac autonomic neuropathy (CAN) is a serious complication of longstanding diabetes and is associated with an increased morbidity and reduced quality of life in patients with diabetes. The present study evaluated the prevalence of CAN diagnosed by reduced heart rate variability (HRV) using...... a newly developed device in a large, unselected, hospital-based population of patients with diabetes....

  15. Painful Diabetic Neuropathy in Japanese Diabetic Patients Is Common but Underrecognized

    Directory of Open Access Journals (Sweden)

    Mayumi Tsuji

    2013-01-01

    Full Text Available Although chronic pain due to diabetic neuropathy, defined as painful diabetic neuropathy (PDN, is a debilitating and distressing complication of diabetes, epidemiological data on PDN has been scarce, especially in Asia. We evaluated the prevalence of Japanese PDN and its impact on their quality of life (QOL and metnal state. In addition, we examined to which extent physicians are aware of patients’ PDN. A total of 298 patients with diabetes were found to be eligible for the study. We revealed that substantial percentage (22.1% of Japanese diabetic patients had PDN and that PDN had negative effect on patients’ QOL and mental state. However, physicians were aware of PDN in only 36.4% of patients with the condition. To the best of our knowledge, this is the first report showing the extent of physicians’ awareness of patients’ PDN. In conclusion, physicians treating diabetes need to be more aware of patients’ PDN in everyday clinical practice to prevent the progression of PDN and improve the patients’ QOL and mental state.

  16. Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy?

    DEFF Research Database (Denmark)

    Kastrup, J; Petersen, P; Dejgård, A

    1987-01-01

    In a randomized double-blind, cross-over study the effect of intravenous lidocaine (5 mg/kg body weight) on the symptoms and signs of painful diabetic neuropathy of more than 6 months duration has been evaluated. Using a clinical symptom scale, there was significant beneficial effect 1 and 8 days...... alternative treatment of chronic painful diabetic neuropathy....... after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new...

  17. Tadalafil Promotes the Recovery of Peripheral Neuropathy in Type II Diabetic Mice.

    Science.gov (United States)

    Wang, Lei; Chopp, Michael; Szalad, Alexandra; Lu, XueRong; Jia, LongFei; Lu, Mei; Zhang, Rui Lan; Zhang, Zheng Gang

    2016-01-01

    We previously demonstrated that treatment of diabetic peripheral neuropathy with the short (4 hours) half-life phosphodiesterase 5 (PDE5) inhibitor, sildenafil, improved functional outcome in diabetic db/db mice. To further examine the effect of PDE5 inhibition on diabetic peripheral neuropathy, we investigated the effect of another potent PDE5 inhibitor, tadalafil, on diabetic peripheral neuropathy. Tadalafil is pharmacokinetically distinct from sildenafil and has a longer half-life (17+hours) than sildenafil. Diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db) at age 20 weeks were treated with tadalafil every 48 hours for 8 consecutive weeks. Compared with diabetic mice treated with saline, tadalafil treatment significantly improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal sensitivity. Tadalafil treatment also markedly increased local blood flow and the density of FITC-dextran perfused vessels in the sciatic nerve concomitantly with increased intraepidermal nerve fiber density. Moreover, tadalafil reversed the diabetes-induced reductions of axon diameter and myelin thickness and reversed the diabetes-induced increased g-ratio in the sciatic nerve. Furthermore, tadalafil enhanced diabetes-reduced nerve growth factor (NGF) and platelet-derived growth factor-C (PDGF-C) protein levels in diabetic sciatic nerve tissue. The present study demonstrates that tadalafil increases regional blood flow in the sciatic nerve tissue, which may contribute to the improvement of peripheral nerve function and the amelioration of diabetic peripheral neuropathy.

  18. PL37: a new hope in the treatment of painful diabetic neuropathy?

    Science.gov (United States)

    Tesfaye, Solomon

    2016-04-01

    Solomon Tesfaye speaks to Nick Ward, Commissioning Editor: Solomon Tesfaye, MB ChB, MD, FRCP, speaks about PL37; the first orally administered dual inhibitor of enkephalinases and its potential role in the treatment of painful diabetic neuropathy. Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield. His research projects include the epidemiology, risk factors, pathogenesis, CNS involvement and treatment of diabetic neuropathy and neuropathic pain. He was awarded the Prestigious Camillo Golgi Prize of the European Association for the Study of Diabetes (EASD) in 2014 for major scientific contributions in diabetic neuropathy. He has had international leadership roles including chairmanship of the International Expert Group on Diabetic Neuropathy, and of NEURODIAB (2006-2009). He is also a member of the Science and Research Committee of Diabetes UK; a review panel member for the MRC, a Board Member of the Global Quantitative Sensation Testing Society; a member of the Advisory Council of the Neuropathy Trust; and Secretary of International Insulin Foundation. He has served as a member of the MRC, JDRF, NIDDK and UK NIHR scientific review panels and as a member of a Diabetes and Neuropathic Pain Review Group for NICE.

  19. [sup 123]I-MIBG myocardial scintigraphy in diabetic patients. Association with autonomic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagamachi, Shigeki; Hoshi, Hiroaki; Ohnishi, Takashi; Jinnouchi, Seishi; Futami, Shigemi; Watanabe, Katsushi; Nakatsuru, Kuninobu; Toshimori, Toshitaka; Matsukura, Shigeru (Miyazaki Medical Coll., Kiyotake (Japan))

    1994-09-01

    [sup 123]I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 20 diabetic patients (NIDDM) and 8 control subjects to investigate the association between clinical autonomic nerve dysfunction and myocardial accumulation of MIBG. We used coefficient variance of R-R interval (CV[sub R-R]) as a index of the autonomic neuropathy and categorized diabetes into two groups (CV[sub R-R][>=]2.0: non-autonomic neuropathy. CV[sub R-R]<2.0: autonomic neuropathy). In planar imaging studies, heart to mediastinum MIBG uptake ratio (H/M) was calculated on both early and delayed images. The washout ratio of [sup 123]I-MIBG in the heart (%WR) was also obtained using myocardial tracer activity on the both images. Mean value of these indices in diabetic group did not reveal any significant difference with the value in the control group. On the SPECT images, low uptake was observed in the posterior-inferior wall with normal uptake of [sup 201]Tl in diabetic patients with non-autonomic neuropathy. These areas extended in patients with autonomic neuropathy. The mean value of count ratio of posterior-interior to anterior wall (posterior-inferior/anterior ratio: PI/A) in the diabetic autonomic neuropathy group was significantly higher than in the control group on the both early and delayed images. And the mean value of regional %WR in the posterior-inferior wall calculated by the both MIBG SPECT images was significantly higher in the non-autonomic neuropathy group than in the control group. In the diabetic patients, retention mechanism of [sup 123]I-MIBG was considered to be involved at an early stage without autonomic nerve dysfunction clinically. As autonomic neuropathy progressed severely, uptake mechanism was also supposed to be involved. Therefore, [sup 123]I-MIBG myocardial scintigraphy was useful for early detection of cardiac sympathetic nervous dysfunction in diabetic patients. (author).

  20. Cardiovascular Autonomic Neuropathy Is Associated With Macrovascular Risk Factors in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Fleischer, Jesper; Yderstraede, Knud; Gulichsen, Elisabeth

    2014-01-01

    The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN. The DAN-Study is a Danish...... multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified......, whereas in type 2 CAN was associated with macrovascular risk factors....

  1. Medial arterial calcification, calcific aortic stenosis and mitral annular calcification in a diabetic patient with severe autonomic neuropathy.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Medial arterial calcification (Monckeberg\\'s arteriosclerosis) is well described in diabetic patients with autonomic neuropathy. There is also a high prevalence of diabetes mellitus among subjects with calcific aortic stenosis and mitral annular calcification. We describe a diabetic patient with autonomic neuropathy and extensive medial arterial calcification who also had calcification of the aortic valve and of the mitral valve annulus. We propose that autonomic neuropathy may play a role in calcification of these structures at the base of the heart.

  2. Effect of C-Peptide on Diabetic Neuropathy in Patients with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Karin Ekberg

    2008-01-01

    Full Text Available Recent results indicate that proinsulin C-peptide, contrary to previous views, exerts important physiological effects and shows the characteristics of a bioactive peptide. Studies in type 1 diabetes, involving animal models as well as patients, demonstrate that C-peptide in replacement doses has the ability to improve peripheral nerve function and prevent or reverse the development of nerve structural abnormalities. Peripheral nerve function, as evaluated by determination of sensory nerve conduction velocity and quantitative sensory testing, is improved by C-peptide replacement in diabetes type 1 patients with early stage neuropathy. Similarly, autonomic nerve dysfunction is ameliorated following administration of C peptide for up to 3 months. As evaluated in animal models of type 1 diabetes, the improved nerve function is accompanied by reversal or prevention of nerve structural changes, and the mechanisms of action are related to the ability of C-peptide to correct diabetes-induced reductions in endoneurial blood flow and in Na+,K+-ATPase activity and modulation of neurotrophic factors. Combining the results demonstrates that C-peptide may be a possible new treatment of neuropathy in type 1 diabetes.

  3. Reproducibility of parameters for assessment of diabetic neuropathy. The French Group for Research and Study of Diabetic Neuropathy.

    Science.gov (United States)

    Valensi, P; Attali, J R; Gagant, S

    1993-12-01

    This study evaluated the reproducibility of nerve function assessment in a group of 132 diabetic patients with moderate peripheral polyneuropathy. Patients were investigated at the beginning and the end of the run-in period (a 1-month placebo period) of a multicentre trial of an aldose-reductase inhibitor (Ponalrestat). Reproducibility was evaluated by performing four types of tests: quantitative visual scales of symptoms, quantitative sensory assessment (vibration perception thresholds in medial malleolus and great toe, foot thermal perception threshold to hot and cold), electrophysiological investigations on the dominant side (conduction velocities and potential amplitudes of sensory and median motor nerve, sural and peroneal nerves, amplitudes of F waves of median motor and peroneal nerves) and cardiac autonomic tests (Valsalva, deep-breathing, lying-to-standing). Reproducibility was poor for symptoms, thermal sensitivity, and potential amplitudes. It was satisfactory (total coefficient of variation waves and the three autonomic tests. For most of the parameters total variance was mainly related to inter-subject variability. However, inter-subject variability for the three cardiac autonomic tests was very low and at least one cardiac autonomic test was altered in all the patients. Inter-centre variability was low for all the parameters, except for action potential amplitudes and for F wave velocity of the median motor nerve. This study suggests those parameters that are appropriate for the assessment of diabetic neuropathy and for therapeutic trials.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special Clinical, Diagnostic, and Prognostic Importance.

    Science.gov (United States)

    Körei, A E; Istenes, I; Papanas, N; Kempler, P

    2016-01-01

    Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.

  5. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

    OpenAIRE

    Davidson, Eric P.; Coppey, Lawrence J.; Amey Holmes; Sergey Lupachyk; Dake, Brian L.; Oltman, Christine L.; Peterson, Richard G.; Yorek, Mark A.

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers,...

  6. Current Status of Diabetic Peripheral Neuropathy in Korea: Report of a Hospital-Based Study of Type 2 Diabetic Patients in Korea by the Diabetic Neuropathy Study Group of the Korean Diabetes Association

    Directory of Open Access Journals (Sweden)

    Jong Chul Won

    2014-02-01

    Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.

  7. [Severe periodontitis, edentulism and neuropathy in patients with type 2 diabetes mellitus].

    Science.gov (United States)

    Menchaca-Díaz, Rufino; Bogarín-López, Bernardo; Zamudio-Gómez, Miguel Alberto; Anzaldo-Campos, María Cecilia

    2012-01-01

    Periodontitis is a frequent pathologic condition in diabetic patient, and has been associated with chronic complications like nephropathy, cardiovascular disease, peripheral artery disease or death. To document the association between severe periodontitis and edentulism with the presence of sensory-motor neuropathy in diabetic patients. Cross-sectional study in type 2 diabetic patients from the family medicine unit no. 27 of the IMSS in Tijuana, México. Patients were evaluated to identify periodontitis and sensory-motor neuropathy. Information was also obtained about sex, age, duration of diabetes, glycemic control, smoking and alcohol use. Four hundred and thirty-six patients completed all measurements. In 180 (41.3%) neuropathy was identified, and associated with age (p diabetes (p periodontitis (OR: 2.7; IC 95%: 1.5-4.8);and with edentulism (OR: 4.4; IC 95%: 2.0-9.4). Logistic regression multivariable analysis kept as significative the association between severe periodontitis and edentulism with neuropathy (adjusted OR: 1.7; IC 95%: 1.1-2.6). Periodontitis and edentulism are associated with the presence of neuropathy in diabetic patients.

  8. Curcumin ameliorated diabetic neuropathy partially by inhibition of NADPH oxidase mediating oxidative stress in the spinal cord.

    Science.gov (United States)

    Zhao, Wei-Cheng; Zhang, Bin; Liao, Mei-Juan; Zhang, Wen-Xuan; He, Wan-You; Wang, Han-Bing; Yang, Cheng-Xiang

    2014-02-07

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main enzymes that produce oxidative stress, which plays an important role in painful diabetic neuropathy. Curcumin has been reported to exert an antinociceptive effect in a rat model of diabetic neuropathy by suppressing oxidative stress in the spinal cord. However, it remains unknown whether the mechanism by which curcumin ameliorates diabetic neuropathy can be attributed to spinal NADPH oxidases. This study was designed to determine the effect of curcumin on diabetic neuropathy and to investigate its precise mechanism in relation to NADPH oxidase-mediating oxidative stress in the spinal cord. Diabetic neuropathy was induced in Sprague-Dawley rats by intraperitoneal injection with 1% streptozotocin (STZ; 60 mg/kg). After the onset of diabetic neuropathy, a subset of the diabetic rats received daily intragastric administrations of curcumin (200mg/kg) or intraperitoneal injections of apocynin (2.5mg/kg) for 14 consecutive days, whereas other diabetic rats received equivalent volumes of normal saline (NS). STZ resulted in diabetic neuropathy with hyperglycemia and a lower paw withdrawal threshold (PWT), accompanied by elevations in the expression of the NADPH oxidase subunits p47(phox) and gp91(phox) and in the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and a reduction in superoxide dismutase (SOD) activity (Pdiabetic neuropathy. In conclusion, curcumin attenuated neuropathic pain in diabetic rats, at least partly by inhibiting NADPH oxidase-mediating oxidative stress in the spinal cord.

  9. Noradrenaline and isoproterenol kinetics in diabetic patients with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Hilsted, J; Christensen, N J

    1986-01-01

    Noradrenaline and isoproterenol kinetics using intravenous infusion of L-3H-NA and of 3H-isoproterenol were investigated in eight Type 1 (insulin-dependent) diabetic patients without neuropathy and in eight Type 1 diabetic patients with autonomic neuropathy matched for age, sex and duration...... of diabetes. Resting plasma noradrenaline and adrenaline concentrations were reduced in patients with autonomic failure (p less than 0.05). The metabolic clearance rate of noradrenaline was similar in both groups of patients, and the appearance rate of noradrenaline in plasma was reduced in patients...

  10. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients.

    Science.gov (United States)

    Singh, A K; Kumar, A; Karmakar, D; Jha, R K

    2013-01-01

    Long-term metformin use has been hypothesized to cause B12 deficiency and neuropathy in Type 2 diabetes patients. However, there is a paucity of Indian data regarding the same. To compare the prevalence of B12 deficiency and peripheral neuropathy in patients with Type 2 diabetes mellitus treated with or without metformin. We recruited patients with Type 2 diabetes and divided them into metformin exposed and nonmetformin exposed groups. We measured baseline demographic variables like age, sex, vegetarian status, and HbA1c levels in both groups. We compared vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS)) in both groups. Definite B12 deficiency was defined as B12 diabetes patients.

  11. Sympathetic mediated vasomotion and skin capillary permeability in diabetic patients with peripheral neuropathy

    NARCIS (Netherlands)

    Lefrandt, JD; Hoeven, JH; Roon, AM; Smit, AJ; Hoogenberg, K

    2003-01-01

    Aims/hypothesis. A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary leaka

  12. Study on the use of quantitative ultrasound evaluation of diabetic neuropathy in the rat sciatic nerve.

    Science.gov (United States)

    Huang, Yunxia; Hu, Bing; Zhu, Jiaan

    2016-12-01

    Ultrasound is an effective tool for peripheral disease with direct imaging of morphological and echogenic changes, but it has limitations when applied to evaluation of diabetic peripheral neuropathy. The aim of this study was to assess the role of ultrasound to quantitatively evaluate diabetic peripheral neuropathy in rat sciatic nerve. In our experiments, ultrasound imaging and electrophysiological examination testing of sciatic nerves were monitored in diabetic and control rats at the period of 1st and 4th month of hyperglycemia. Cross sectional area, intraneural echo intensity, inner diameter, motor nerve conduction velocity, and histological changes were measured and compared between diabetic and control groups. Intraneural hyperechoic were observed in the diabetic rats, and the echo intensity of the sciatic nerve was increased in diabetic rats rather than control lean rats at 4th month of hyperglycemia (p diabetic peripheral neuropathy. We conclude that the echo intensity is potentially useful in detecting diabetic peripheral neuropathy, which can pave the way for more accurate and efficient diagnosis in clinical study.

  13. Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy.

    Science.gov (United States)

    Alam, Uazman; Jeziorska, Maria; Petropoulos, Ioannis N; Asghar, Omar; Fadavi, Hassan; Ponirakis, Georgios; Marshall, Andrew; Tavakoli, Mitra; Boulton, Andrew J M; Efron, Nathan; Malik, Rayaz A

    2017-01-01

    Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against a range of established measures of nerve damage in patients with diabetic neuropathy. In this cross sectional study, thirty subjects with Type 1 diabetes without neuropathy (T1DM), thirty one T1DM subjects with neuropathy (DSPN) and twenty seven non-diabetic healthy control subjects underwent detailed assessment of neuropathic symptoms and neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy and corneal confocal microscopy (CCM). Subjects with DSPN were older (C vs T1DM vs DSPN: 41.0±14.9 vs 38.8±12.5 vs 53.3±11.9, P = 0.0002), had a longer duration of diabetes (P<0.0001), lower eGFR (P = 0.006) and higher albumin-creatinine ratio (P = 0.03) with no significant difference for HbA1c, BMI, lipids and blood pressure. Patients with DSPN were representative of subjects with diabetic neuropathy with clinical signs and symptoms of neuropathy and greater neuropathy deficits quantified by QST, electrophysiology, intra-epidermal nerve fibre density and CCM. Corneal nerve fibre density (CNFD) (Spearman's Rho = 0.60 P<0.0001) and IENFD (Spearman's Rho = 0.56 P<0.0001) were comparable when correlated with peroneal nerve conduction velocity. For the diagnosis of diabetic neuropathy the sensitivity for CNFD was 0.77 and specificity was 0.79 with an area under the ROC curve of 0.81. IENFD had a diagnostic sensitivity of 0.61, specificity of 0.80 and area under the ROC curve of 0.73. CCM is a valid accurate non-invasive method to identify small nerve fibre pathology and is able to diagnose DPN.

  14. Pulmonary function tests in type 1 diabetes adolescents with diabetic cardiovascular autonomic neuropathy.

    Science.gov (United States)

    Ďurdík, Peter; Vojtková, Jarmila; Michnová, Zuzana; Turčan, Tomáš; Šujanská, Anna; Kuchta, Milan; Čiljaková, Miriam

    2016-01-01

    Chronic diabetic complications may afflict all organ tissues including cardiovascular and respiratory system. The aim of the study was to establish if the presence of cardiovascular autonomic neuropathy (CAN) was associated with impaired pulmonary function tests in adolescents with type 1 diabetes (T1D). 46 adolescents with T1D and 25 healthy subjects at the age 15-19years were enrolled to the study. Basic anthropometric data, diabetes onset and duration, plasma glucose and A1c were established. Pulmonary function tests were measured by spirometry and the presence of CAN was examined by heart rate variability. Adolescents with T1D had significantly lower pulmonary function test parameters - FVC (ppulmonary functions in adolescents with T1D.

  15. Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Somsuvra B. Ghatak

    2012-10-01

    Full Text Available Several studies have implicated the involvement of poor glycemic control and oxidative/nitrosative stress in the development of diabetic neuropathic pain, an important microvascular complication affecting more than 50% of diabetic patients. However, lack of understanding of the underlying etiology, development of tolerance, inadequate relief and possible toxicity associated with classical analgesics warrant the investigation of the novel agents. Therefore, the present study was carried out to investigate the effect of oryzanol (OZ, a commercially-important potent antioxidant component isolated from from crude rice bran oil (cRBO, in streptozotocin (STZ-induced diabetic neuropathy in rats. After eight weeks, diabetic rats developed neuropathy which was evident from decreased tail-flick latency (thermal hyperalgesia and increased nociceptive behavior during the formalin test. This was accompanied by decreased motor coordination based on the evaluation of neuromuscular strength. Na+ K+ ATPase, a biochemical marker associated with the development of diabetic neuropathy, was significantly inhibited in the sciatic nerve of diabetic animals. The activities of antioxidant enzymes and lipid peroxidation levels were significantly elevated in diabetic rats, indicating the involvement of oxidative stress in diabetic neuropathy. Chronic treatment with oryzanol (OZ (50 and 100 mg/kg per oral (p.o. and standard drug glibenclamide (Gl (10 mg/kg, p.o. significantly attenuated the behavioral as well as biochemical changes associated with diabetic neuropathy. The findings provide experimental evidence to the protective effects of OZ on hyperglycemia-induced thermal hyperalgesia and oxidative stress which might be responsible for diabetes induced nerve damage.

  16. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hansen, Christian S; Jensen, Jan S; Ridderstråle, Martin

    2017-01-01

    AIMS: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients. METHODS: 469 ambulatory type 2 diabetes patients (mean diabetes.......01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025). CONCLUSION: Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN...

  17. Exocrine Pancreatic Insufficiency in Diabetes Mellitus: A Complication of Diabetic Neuropathy or a Different Type of Diabetes?

    Directory of Open Access Journals (Sweden)

    Philip D. Hardt

    2011-01-01

    Full Text Available Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis. Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

  18. Corneal Confocal Microscopy – A Novel, Noninvasive Method to Assess Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Inceu Georgeta

    2014-12-01

    Full Text Available Background and aims. This article aims to compare corneal confocal microscopy (CCM with acknowledged tests of diabetic peripheral neuropathy (DPN, to assess corneal nerve morphology using CCM in diabetic patients, and to underline possible correlations between clinical and biological parameters, diabetes duration and DPN severity. Material and methods. A total of 90 patients with type 2 diabetes were included in the study for whom we measured anthropometric parameters and we performed laboratory measurements (tests. The patients were assessed for diabetic peripheral neuropathy using Semmes-Weinstein Monofilament Testing (SWMT, Rapid-Current Perception Threshold (R-CPT measurements using the Neurometer®, and CCM. We stratified the patients according to DPN severity, based on four parameters extracted after image analysis. Results. A higher percentage of patients were diagnosed with DPN using CCM (88.8%, compared with SWMT and R-CPT measurement (17.8% and 40% respectively. The incidence of DPN detected with CCM was considerable in patients with normal protective sensation and with normal R-CPT values. Conclusions. Our study showed that corneal confocal microscopy is a useful noninvasive method for diabetic neuropathy assessement in early stages. It was proven to directly quantify small fiber pathology, and to stratify neuropathic severity, and therefore can be used as a new, reliable tool in the diagnosis, clinical evaluation, and follow-up of peripheral diabetic neuropathy.

  19. Plantar pressure distribution patterns during gait in diabetic neuropathy patients with a history of foot ulcers

    Directory of Open Access Journals (Sweden)

    Tatiana Almeida Bacarin

    2009-02-01

    Full Text Available OBJECTIVE: To investigate and compare the influence of a previous history of foot ulcers on plantar pressure variables during gait of patients with diabetic neuropathy. INTRODUCTION: Foot ulcers may be an indicator of worsening diabetic neuropathy. However, the behavior of plantar pressure patterns over time and during the progression of neuropathy, especially in patients who have a clinical history of foot ulcers, is still unclear. METHODS: Subjects were divided into the following groups: control group, 20 subjects; diabetic neuropathy patients without foot ulcers, 17 subjects; and diabetic neuropathy patients with at least one healed foot ulcer within the last year, 10 subjects. Plantar pressure distribution was recorded during barefoot gait using the Pedar-X system. RESULTS: Neuropathic subjects from both the diabetic neuropathy and DNU groups showed higher plantar pressure than control subjects. At midfoot, the peak pressure was significantly different among all groups: control group (139.4±76.4 kPa, diabetic neuropathy (205.3±118.6 kPa and DNU (290.7±151.5 kPa (p=0.008. The pressure-time integral was significantly higher in the ulcerated neuropathic groups at midfoot (CG: 37.3±11.4 kPa.s; DN: 43.3±9.1 kPa.s; DNU: 68.7±36.5 kPa.s; p=0.002 and rearfoot (CG: 83.3±21.2 kPa.s; DN: 94.9±29.4 kPa.s; DNU: 102.5±37.9 kPa.s; p=0.048. CONCLUSION: A history of foot ulcers in the clinical history of diabetic neuropathy subjects influenced plantar pressure distribution, resulting in an increased load under the midfoot and rearfoot and an increase in the variability of plantar pressure during barefoot gait. The progression of diabetic neuropathy was not found to influence plantar pressure distribution.

  20. Alternative Quantitative Tools in the Assessment of Diabetic Peripheral and Autonomic Neuropathy.

    Science.gov (United States)

    Vinik, A I; Casellini, C; Névoret, M-L

    2016-01-01

    Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss.

  1. Cardiac autonomic neuropathy in patients with uraemia is not related to pre-diabetes

    DEFF Research Database (Denmark)

    Elming, Marie Bayer; Hornum, Mads; Feldt-Rasmussen, Bo

    2011-01-01

    INTRODUCTION: It has been proposed that pre-diabetes may cause neuropathy. The aim of this study was to investigate whether cardiac autonomic neuropathy (CAN) in uraemic patients was related to the presence of pre-diabetes. MATERIAL AND METHODS: The study included 66 non-diabetic uraemic patients...... enrolled. Beat-to-beat variability was determined from the echocardiographic recording during deep inspiration and expiration. CAN was defined as a beat-to-beat value below 10 beats/min. Pre-diabetes was defined as presence of impaired fasting glucose and/or impaired glucose tolerance measured by oral...... glucose tolerance test (WHO/American Diabetes Association criteria 2007). RESULTS: The prevalence of CAN was 38% in uraemic patients compared with 8% in the controls (p diabetic, while the remaining 39 had a normal glucose tolerance...

  2. Seminal vesicles and diabetic neuropathy: ultrasound evaluation after prolonged treatment with a selective phosphodiesterase-5 inhibitor.

    Science.gov (United States)

    La Vignera, S; Condorelli, R A; Vicari, E; Lotti, F; Favilla, V; Morgia, G; Maggi, M; Calogero, A E

    2013-03-01

    We have previously reported that infertile patients with diabetes mellitus (DM) have a particular ultrasound features of the seminal vesicles (SV) characterized by higher fundus-to-body ratio and lower pre- and post-ejaculatory difference in body antero-posterior diameter (APD). Based on these premises the aim of the present study was to investigate possible ultrasound SV changes in infertile patients with DM and diabetic neuropathy (DN), after prolonged administration of tadalafil (TAD) (a specific phosphodiesterase-5 inhibitor). To accomplish this, 20 infertile patients with symptomatic DN and erectile dysfunction were selected and arbitrarily divided into two groups which were assigned to: daily administration of 5 mg TAD for 3 months (Group A) (n = 10) and administration of placebo (Group B) (n = 10). All patients underwent to scrotal and prostate-vesicular transrectal ultrasound evaluation and semen analysis (Laboratory Manual for the Examination and Processing of Human Semen, WHO, 2010) before and after treatment. The following SV US parameters were recorded: (i) body APD; (ii) fundus APD; (iii) parietal thickness of the right and left SVs; and (iv) number of polycyclic areas within both SVs. We then calculated the following parameters: (i) fundus/body (F/B) ratio; (ii) difference of the parietal thickness between the right and the left SV and (iii) pre- and post-ejaculatory APD difference. In addition, we also evaluated the SV ejection fraction. Group A patients showed a significant reduction in F/B ratio and higher pre- and post-ejaculatory body SV APD difference compared with baseline or Group B after 3 months. These patients showed also a significant increase in SV ejection fraction and a significant improvement of the total sperm count, progressive motility, seminal levels of fructose, leucocytes and ejaculate volume. In conclusion, these results suggest that infertile DM patients with DN and erectile dysfunction had an improvement of ultrasound features

  3. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats.

    Science.gov (United States)

    Gregory, Joshua A; Jolivalt, Corinne G; Goor, Jared; Mizisin, Andrew P; Calcutt, Nigel A

    2012-10-01

    Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behavioral, physiological and structural indices of neuropathy were measured for up to 6 months in spontaneously hypertensive and age-matched normotensive rats with or without concurrent streptozotocin-induced diabetes. Hypertensive rats developed nerve ischemia, thermal hyperalgesia, nerve conduction slowing and axonal atrophy. Thinly myelinated fibers with supernumerary Schwann cells indicative of cycles of demyelination and remyelination were also identified along with reduced nerve levels of myelin basic protein. Similar disorders were noted in streptozotocin-diabetic rats, except that thinly myelinated fibers were not observed and expression of myelin basic protein was normal. Superimposing diabetes on hypertension compounded disorders of nerve blood flow, conduction slowing and axonal atrophy and increased the incidence of thinly myelinated fibers. Rats with combined insulinopenia, hyperglycemia and hypertension provide a model for diabetic neuropathy that offers an opportunity to study mechanisms of Schwann cell pathology and suggests that hypertension may contribute to the etiology of diabetic neuropathy.

  4. ANALGELSIC EFFECT OF BUPRENORPHINE IN AN EXPERIMENTAL MODEL OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY

    OpenAIRE

    Chiorazzi, A; Carozzi, V; Canta, A; Meregalli, C.; Oggioni, N; Bianchi, R; Lombardi, R.; Camozzi, F; Lauria, G.; Cavaletti, G

    2008-01-01

    AIM: Diabetic peripheral neuropathy (DPN) is a complication of inadequately treated diabetes mellitus leading to sensory loss and neuropathic pain. DPN of different severity is present during in the majority of diabetic patients. Although most patients with DPN do not have pain, a clinically-relevant proportion of them complain of chronic painful symptoms that affect their quality of life, disrupt sleep, and can lead to depression. Recent advances in understanding DPN-associated pain are like...

  5. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress

    OpenAIRE

    Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

    2009-01-01

    Abstract Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats w...

  6. Nerve Regeneration Should Be Highly Valued in the Treatment of Diabetic Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao-chun

    2008-01-01

    @@ Diabetic peripheral neuropathy (DPN) is the most common chronic complication of the long-term complications of diabetes, affecting up to 90% of patients during the progress of the disease. Many parts of the nerve system, including the sensory nerves, motor nerves and autonomic nerves, can be affected, leading to various clinical features. DPN leads not only to a great degree of mutilation and death but also to the occurrence and development of other long-term complications in diabetics.

  7. Thalidomide Promotes Morphine Efficacy and Prevents Morphine-Induced Tolerance in Rats with Diabetic Neuropathy.

    Science.gov (United States)

    Zhao, Jianhui; Wang, Hong; Song, Tieying; Yang, Yunliang; Gu, Kunfeng; Ma, Pengyu; Zhang, Zaiwang; Shen, Limin; Liu, Jiabao; Wang, Wenli

    2016-12-01

    Opioid analgesics have less efficacy in diabetic neuropathy treatment, and tolerance often occurs after chronic usage. Given that thalidomide can potentiate the morphine efficacy in diabetic neuropathy treatment, we investigated the effects of intrathecal administrations of thalidomide on morphine tolerance during the treatment of diabetic neuropathy. We found that intrathecal administrations of thalidomide (25 mg/kg/ml) potentiated the analgesic effects of morphine on mechanical hyperalgesia and prevented the development of morphine tolerance. While this treatment regimen did not alter the protein levels of μ-opioid receptor (MOR) in the spinal cord of diabetic rats, chronic morphine treatment robustly increased MOR binding density in the synaptic plasma membranes fraction, but decreased it in the microsomal fraction. Furthermore, thalidomide was able to reverse the distribution of MOR altered by chronic morphine treatment. Finally, STZ-induced diabetes promoted PKC activation and enhanced TNFα level in the spinal cord, which were attenuated by intrathecal administrations of thalidomide. Taken together, these results suggested that thalidomide may potentiate morphine efficacy on diabetic neuropathy and prevent the development of morphine tolerance by suppressing PKC activation and TNFα level in the spinal cord.

  8. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Eric P. Davidson

    2014-01-01

    Full Text Available Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

  9. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin.

    Science.gov (United States)

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2015-10-05

    Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenuate hyperexcitability in sensory neurons linked to chemotherapy-induced neuropathic pain, highlighting its potential in alleviating pain related with painful diabetic neuropathy. The present study was designed to investigate the potential beneficial effect of metformin on hyperalgesia and allodynia in diabetic rats. The mechanical sensitivity, heat nociception, and cold allodynia were examined. The levels of malondialdehyde, superoxide dismutase, and advanced glycation end-products in the blood were measured. The expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and AMPK target genes were examined in the sciatic nerves of the animals. It was found that metformin was capable of attenuating diabetes-induced mechanical hyperalgesia, heat hyperalgesia and cold allodynia. In addition, metformin was capable of decreasing malondialdehyde and glycation end-products levels in blood, as well as increasing superoxide dismutas activity, indicating the inhibitory effect of metformin against diabetes-induced oxidative stress. Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats. In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway. Metformin might be used as an effective drug, especially with fewer side effects, for abnormal sensation in painful diabetic neuropathy.

  10. Novel systems for in vivo monitoring and microenvironmental investigations of diabetic neuropathy in a murine model.

    Science.gov (United States)

    Amit, Sharon; Yaron, Avraham

    2012-11-01

    Peripheral neuropathy is a devastating complication of diabetes conferring vast morbidity and mortality. Despite prolonged efforts to elucidate the mechanisms underlying diabetic related neuropathic phenomena and develop effective therapies, current treatment is for the most part glycemic control and symptomatic care. This is partially due to the intricate pathophysiology of diabetic neuropathy and the scarcity of valid experimental models. The aim of the study was to establish novel systems enabling monitoring and dissection of significant processes in the development of diabetic neuropathy. In a non-invasive in vivo model, two-photon microscopy is applied to evaluate mechanoreceptors (Meissner corpuscles) within an intact footpad of transgenic mice expressing a fluorescent neuronal tracer. By applying this advanced technology, which couples potent tissue penetration with superb resolution, we documented qualitative and quantitative diabetes-specific alterations in these sensory structures. Detection of such changes previously required laborious invasive histopathological techniques. In parallel, we present an ex vivo system that mimics the native microenvironment of the nerve ending via a unique co-culture of primary sensory neurons and thin skin slices. In conjunction with innovative high-throughput digital axonal measurements and computerized quantification tools, this method enables an unbiased exploration of neuronal autonomous and non-autonomous malfunctions. Using this setup we demonstrate that while the diabetic nerve retains a near-normal growth and regeneration capacities, the diabetic skin exhibits a decreased ability to support axonal outgrowth. Thus, an early target organ failure rather than intrinsic neuronal failure may initiate the neuropathy. Overall, the illustrated experimental platforms may greatly facilitate the holistic investigation of diabetic neuropathy.

  11. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood.

    Science.gov (United States)

    Max, M B; Culnane, M; Schafer, S C; Gracely, R H; Walther, D J; Smoller, B; Dubner, R

    1987-04-01

    In a randomized, double-blind crossover study, 29 patients with painful diabetic neuropathy received 6 weeks of amitriptyline and 6 weeks of an "active" placebo that mimicked amitriptyline side effects. Amitriptyline was superior to placebo in relieving pain in weeks 3 through 6. Both steady, burning pain and lancinating pains were relieved. Patients able to tolerate higher amitriptyline doses reported greater relief, through the maximum dose of 150 mg nightly. Amitriptyline analgesia was similar in depressed and nondepressed subgroups and was not associated with mood improvement. We conclude that amitriptyline relieves pain in diabetic neuropathy; this effect is independent of mood elevation.

  12. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomised clinical trial

    DEFF Research Database (Denmark)

    de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades

    2014-01-01

    Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our......D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced...

  13. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Zohreh Rahimi

    2014-01-01

    Full Text Available Background: The renin angiotensin aldosterone system (RAAS plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM and its complications of retinopathy, neuropathy and cardiovascular disease (CVD. Materials and Methods: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM, T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR, diabetic neuropathy and cardiovascular complication of DM. Results: The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D and angiotensin II type 1 receptor gene (AT1R A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients. Conclusion: More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.

  14. Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.

    Science.gov (United States)

    Laczy, Boglárka; Cseh, Judit; Mohás, Márton; Markó, Lajos; Tamaskó, Mónika; Koszegi, Tamás; Molnár, Gergo A; Wagner, Zoltán; Wagner, László; Wittmann, István

    2009-06-01

    Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.

  15. Effects of selenium on electrophysiological changes associated with diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Murat Ayaz; Hülagu Kaptan

    2011-01-01

    Our previous study has demonstrated that sodium selenite prevents oxidative stress, suggesting that selenium can improve diabetic peripheral neuropathy. Results from this study demonstrated that diabetes mellitus resulted in significant increased time to peak, as well as rheobase and chronaxie values, In addition, maximum depolarization, area under compound action potential, kinetics, and conduction velocities of fast and stow nerve fiber groups were decreased. Sodium selenite exhibited positive effects on alterations of diabetes mellitus-induced conduction velocity distribution. This neuroprotective effect was primarily observed in the area under compound action potential and compound action potential kinetic waveforms, as well as rheobase and chronaxie. Results from this study showed that selenium supplementation blocked the diabetes mellitus-induced shift of actively contributing nerve fibers, and restored levels towards age-matched control group values. Chronic selenate supplementation for experimental diabetic peripheral neuropathy exhibited protective effects in measured electrophysiological parameters.

  16. Cardiac autonomic neuropathy in patients with uraemia is not related to pre-diabetes

    DEFF Research Database (Denmark)

    Eming, Marie Bayer; Hornum, Mads; Feldt-Rasmussen, Bo Friis

    2011-01-01

    INTRODUCTION: It has been proposed that pre-diabetes may cause neuropathy. The aim of this study was to investigate whether cardiac autonomic neuropathy (CAN) in uraemic patients was related to the presence of pre-diabetes. MATERIAL AND METHODS: The study included 66 non-diabetic uraemic patients...... enrolled. Beat-to-beat variability was determined from the echocardiographic (ECG) recording during deep inspiration and expiration. CAN was defined as a beat-to-beat value below 10 beats/min. Pre-diabetes was defined as presence of impaired fasting glucose and/or impaired glucose tolerance measured...... by oral glucose tolerance test (WHO/American Diabetes Association criteria 2007). RESULTS: The prevalence of CAN was 38% in uraemic patients compared with 8% in the controls (p

  17. The Proinflammatory Cytokine High-Mobility Group Box-1 Mediates Retinal Neuropathy Induced by Diabetes

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abu El-Asrar

    2014-01-01

    Full Text Available To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1 in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2, cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.

  18. Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy.

    Science.gov (United States)

    Vincent, Andrea M; Edwards, James L; McLean, Lisa L; Hong, Yu; Cerri, Federica; Lopez, Ignazio; Quattrini, Angelo; Feldman, Eva L

    2010-10-01

    Mitochondrial-mediated oxidative stress in response to high glucose is proposed as a primary cause of dorsal root ganglia (DRG) neuron injury in the pathogenesis of diabetic neuropathy. In the present study, we report a greater number of mitochondria in both myelinated and unmyelinated dorsal root axons in a well-established model of murine diabetic neuropathy. No similar changes were seen in younger diabetic animals without neuropathy or in the ventral motor roots of any diabetic animals. These findings led us to examine mitochondrial biogenesis and fission in response to hyperglycemia in the neurites of cultured DRG neurons. We demonstrate overall mitochondrial biogenesis via increases in mitochondrial transcription factors and increases in mitochondrial DNA in both DRG neurons and axons. However, this process occurs over a longer time period than a rapidly observed increase in the number of mitochondria in DRG neurites that appears to result, at least in part, from mitochondrial fission. We conclude that during acute hyperglycemia, mitochondrial fission is a prominent response, and excessive mitochondrial fission may result in dysregulation of energy production, activation of caspase 3, and subsequent DRG neuron injury. During more prolonged hyperglycemia, there is evidence of compensatory mitochondrial biogenesis in axons. Our data suggest that an imbalance between mitochondrial biogenesis and fission may play a role in the pathogenesis of diabetic neuropathy.

  19. Effects of Semelil (ANGIPARSTM on diabetic peripheral neuropathy: A randomized, double-blind Placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    S Bakhshayeshi

    2011-03-01

    Full Text Available "n Background and the purpose of the study: Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARSTM, a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. "nMethods: In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARSTM and placebo groups. All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. "nResults: Michigan diabetic neuropathy score was decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARSTM group. Conclusion: The results showed limited evidence of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required.

  20. Increased prevalence of symptoms of gastroesophageal reflux diseases in type 2 diabetics with neuropathy

    Institute of Scientific and Technical Information of China (English)

    Xiangbing Wang; CS Pitchumoni; Khushbu Chandrarana; Neha Shah

    2008-01-01

    AIM:To analyze the prevalence of gastroesophageal reflux disease (GERD) related symptoms in patients with diabetes mellitus (DM) and to find out the relationship between diabetic neuropathy and the prevalence of GERD symptoms.METHODS:In this prospective questionnaire study,150 consecutive type 2 diabetic patients attending the endocrine clinic were enrolled.A junior physician helped the patients to understand the questions.Patients were asked about the presence of five most frequent symptoms of GERD that included heartburn (at least 1/wk),regurgitation,chest pain,hoarseness of voice and chronic cough.Patients with past medical history of angina,COPD,asthma,cough due to ACEI or preexisting GERD prior to onset of diabetes and apparent psychiatric disorders were excluded from the survey.We further divided the patients into two groups based on presence or absence of peripheral neuropathy.Out of 150 patients,46 had neuropathy,whereas 104 patients did not have neuropathy.Data are expressed as mean±SD,and number of patients in each category and percentage of total patients in that group.Normal distributions between groups were compared with Student t test and the prevalence rates between groups were compared with Chi-square tests for significance.RESULTS:The average duration of diabetes were 12±9.2 years and the average HbAlc level of this group was 7.7% + 2.0%.The mean weight and BMI were 198 + 54 Ibs.and 32±7.2 kg/m2.Forty percent (61/150) patients reported having at least one of the symptoms of GERD and thirty percent (45/150) reported having heartburn at least once a week.The prevalence of GERD symptoms is higher in patients with neuropathy than patients without neuropathy (58.7% vs 32.7%,P<0.01).The prevalence of heartburn,chest pain and chronic cough are also higher in patients with neuropathy than in patients without neuropathy (43.5% vs 24%;10.9% vs 4.8%and 17.8% vs 6.7% respectively,P<0.05).CONCLUSION:The prevalence of GERD symptoms in type 2 DM is higher

  1. Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy.

    Science.gov (United States)

    Negi, Geeta; Nakkina, Vanaja; Kamble, Pallavi; Sharma, Shyam S

    2015-12-01

    Diabetic neuropathy is a complex disorder induced by long standing diabetes. Many signaling pathways and transcription factors have been proposed to be involved in the development and progression of related processes. Years of research points to critical role of oxidative stress, neuroinflammation and apoptosis in the pathogenesis of neuropathy in diabetes. Heme oxygenase-1 (HO-1) is heat-shock protein induced under conditions of different kinds of stress and has been implicated in cellular defense against oxidative stress. HO-1 degrades heme to biliverdin, carbon monoxide (CO) and free iron. Biliverdin and CO are gaining particular interest because these two have been found to mediate most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. Although extensively studied in different kinds of cancers and cardiovascular conditions, role of HO-1 in diabetic neuropathy is still under investigation. In this paper, we review the unique therapeutic potential of HO-1 and its role in mitigating various pathological processes that lead to diabetic neuropathy. This review also highlights the therapeutic approaches such as pharmacological and natural inducers of HO-1, gene delivery of HO-1 or its reaction products that in future, could lead to progression of HO-1 activators through the preclinical stages of drug development to clinical trials.

  2. Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.

    Science.gov (United States)

    Zhou, Jiyin; Du, Xiaohuang; Long, Min; Zhang, Zuo; Zhou, Shiwen; Zhou, Jianyun; Qian, Guisheng

    2016-03-05

    The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

  3. Effect of diabetic neuropathy severity classified by a fuzzy model in muscle dynamics during gait.

    Science.gov (United States)

    Watari, Ricky; Sartor, Cristina D; Picon, Andreja P; Butugan, Marco K; Amorim, Cesar F; Ortega, Neli R S; Sacco, Isabel C N

    2014-02-08

    Electromyography (EMG) alterations during gait, supposedly caused by diabetic sensorimotor polyneuropathy, are subtle and still inconsistent, due to difficulties in defining homogeneous experimental groups with a clear definition of disease stages. Since evaluating these patients involve many uncertainties, the use of a fuzzy model could enable a better discrimination among different stages of diabetic polyneuropathy and lead to a clarification of when changes in muscle activation start occurring. The aim of this study was to investigate EMG patterns during gait in diabetic individuals with different stages of DSP severity, classified by a fuzzy system. 147 subjects were divided into a control group (n = 30) and four diabetic groups: absent (n = 43), mild (n = 30), moderate (n = 16), and severe (n = 28) neuropathy, classified by a fuzzy model. The EMG activity of the vastus lateralis, tibialis anterior, and gastrocnemius medialis were measured during gait. Temporal and relative magnitude variables were compared among groups using ANOVA tests. Muscle activity changes are present even before an established neural involvement, with delay in vastus lateralis peak and lower tibialis anterior relative magnitude. These alterations suggest an impaired ankle shock absorption mechanism, with compensation at the knee. This condition seems to be more pronounced in higher degrees of neuropathy, as there is an increased vastus lateralis activity in the mild and severe neuropathy groups. Tibialis anterior onset at terminal stance was anticipated in all diabetic groups; at higher degrees of neuropathy, the gastrocnemius medialis exhibited activity reduction and peak delay. EMG alterations in the vastus lateralis and tibialis anterior occur even in the absence of diabetic neuropathy and in mild neuropathic subjects, seemingly causing changes in the shock absorption mechanisms at the heel strike. These changes increase with the onset of neural impairments, and the gastrocnemius

  4. Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice

    OpenAIRE

    Menichella, Daniela M; Jayaraj, Nirupa D; Wilson, Heather M; Ren, Dongjun; Flood, Kelsey; Wang, Xiao-Qi; Shum, Andrew; Miller, Richard J.; Paller, Amy S.

    2016-01-01

    Background Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown. Purpose Determine whether GM3 depletion is able to reverse neurop...

  5. Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis (Protocol)

    OpenAIRE

    Griebeler Marcio L; Tsapas Apostolos; Brito Juan P; Wang Zhen; Phung Olivia J; Montori Victor M; Murad M

    2012-01-01

    Abstract Background Neuropathic pain can reduce the quality of life and independence of 30% to 50% of patients with diabetes. The comparative effectiveness of analgesics for patients with diabetic neuropathy remains unclear. The aim of the current work, therefore, was to summarize the evidence about the analgesic effectiveness of the most common oral and topical agents used for the treatment of peripheral diabetic neuropathy. Methods We will use an umbrella approach (systematic review of syst...

  6. Effect of flat insoles with different shore A values on posture stability in diabetic neuropathy

    NARCIS (Netherlands)

    Van Geffen, J.A.; Dijkstra, P.U.; Hof, A.L.; Halbertsma, J.P.K.; Postema, K.

    2007-01-01

    The objective of the study was to determine whether insoles with a low Shore A value (15 degrees) as prescribed for patients with a diabetic neuropathy have a negative effect on posture stability because these insoles may reduce somatosensory input under the feet. It was conducted in the Center for

  7. Diabetic Cardiovascular Autonomic Neuropathy Predicts Recurrent Cardiovascular Diseases in Patients with Type 2 Diabetes

    Science.gov (United States)

    Cha, Seon-Ah; Yun, Jae-Seung; Lim, Tae-Seok; Min, Kyoungil; Song, Ki-Ho; Yoo, Ki-Dong; Park, Yong-Moon; Ahn, Yu-Bae

    2016-01-01

    Cardiovascular autonomic neuropathy (CAN) is a risk factor for cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. This study evaluated the relationship between CAN and recurrent CVD in type 2 diabetes. A total of 206 patients with type 2 diabetes who had a history of CVD within 3 years of enrollment were consecutively recruited from January 2001 to December 2009 and followed-up until December 2015. Cardiovascular autonomic function tests were performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver and standing. We estimated the recurrence of CVD events during the follow-up period. A total of 159 (77.2%) of the 206 patients enrolled completed the follow up, and 78 (49.1%) patients had recurrent episodes of CVD, with an incidence rate of 75.6 per 1,000 patient-years. The mean age and diabetes duration were 62.5 ± 8.7 and 9.2 ± 6.9 years, respectively. Patients who developed recurrent CVD also exhibited hypertension (P = 0.004), diabetic nephropathy (P = 0.012), higher mean systolic blood pressure (P = 0.006), urinary albumin excretion (P = 0.015), and mean triglyceride level (P = 0.035) than did patients without recurrent CVD. Multivariable Cox hazard regression analysis revealed that definite CAN was significantly associated with an increased risk of recurrent CVD (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.39−6.60; P = 0.005). Definite CAN was an independent predictor for recurrent CVD in patients with type 2 diabetes who had a known prior CVD event. PMID:27741306

  8. Cardiovascular autonomic neuropathy and subclinical cardiovascular disease in normoalbuminuric type 1 diabetic patients

    DEFF Research Database (Denmark)

    Mogensen, Ulrik Madvig; Jensen, Tonny; Køber, Lars

    2012-01-01

    Cardiovascular autonomic neuropathy (CAN) is associated with increased mortality in diabetes. Since CAN often develops in parallel with diabetic nephropathy as a confounder, we aimed to investigate the isolated impact of CAN on cardiovascular disease in normoalbuminuric patients. Fifty......-six normoalbuminuric, type 1 diabetic patients were divided into 26 with (+) and 30 without (-) CAN according to tests of their autonomic nerve function. Coronary artery plaque burden and coronary artery calcium score (CACS) were evaluated using computed tomography. Left ventricular function was evaluated using...... with increased CACS, subclinical left ventricular dysfunction, and increased pulse pressure. In conclusion, CAN in normoalbuminuric type 1 diabetic patients is associated with distinct signs of subclinical cardiovascular disease....

  9. Impaired noradrenaline homeostasis in rats with painful diabetic neuropathy as a target of duloxetine analgesia

    OpenAIRE

    Kinoshita, Jun; Takahashi, Yukari; Watabe, Ayako M.; Utsunomiya, Kazunori; Kato, Fusao

    2013-01-01

    Background Painful diabetic neuropathy (PDN) is a serious complication of diabetes mellitus that affects a large number of patients in many countries. The molecular mechanisms underlying the exaggerated nociception in PDN have not been established. Recently, duloxetine (DLX), a serotonin and noradrenaline re-uptake inhibitor, has been recommended as one of the first-line treatments of PDN in the United States Food and Drug Administration, the European Medicines Agency and the Japanese Guideli...

  10. SUDOSCAN: A Simple, Rapid, and Objective Method with Potential for Screening for Diabetic Peripheral Neuropathy.

    OpenAIRE

    Selvarajah, D; Cash, T; Davies, J; A. Sankar; Rao, G.; Grieg, M.; S. PALLAI; Gandhi, R.; Wilkinson, I. D; Tesfaye, S.

    2015-01-01

    Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Ne...

  11. Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.

    Science.gov (United States)

    Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugrešić, Nenad; Stepanović-Petrović, Radica

    2015-07-01

    Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy.

  12. EFFECT OF HIGH TENS ON NEUROPATHIC PAIN IN DIABETIC NEUROPATHY PATIENTS

    Directory of Open Access Journals (Sweden)

    Shahanawaz SD

    2014-08-01

    Full Text Available Background: Diabetic Neuropathy is a condition that damages nerve in the body. High blood sugar levels affect the way nerves use glucose leading to an accumulation of sugar SORBITOL as depletion of substance called MYOINOSITOL with in nerves, contributing to nerve damage. Historically De calvi first showed the relationship between diabetes and peripheral nerve damage. Diabetes Mellitus is predicted to afflict 220 Million people worldwide by the year 2010, and approximately 30-60% of patients with Diabetes develop long-term of peripheral neuropathy and upto 10 to 20% of these patients experience pain. Pirart8, showed the incidence of Diabetic Neuropathy to be 7.5% at the time of diagnosis with a 1.7% annual increase. [International Diabetes Federation]. Method: Thirty subjects were divided equally 2 groups each containing subjects Group A were given TENS, (mean age 53.2, while group B was given placebo TENS mean age of 50.8 and Visual Analog Scale [VAS] scores > 5 were calculated and data collected for all the subjects prior to the treatment and after the treatment intervention. Wilcoxon method was used for analysis. Results: The Experimental group (N=15 used TENS, the mean of Pre-treatment VAS Score is 8.46 and Post-treatment VAS Score is 2.6 and statistically when observed by using the Wilcoxon signed ranks test the obtained T Value =7 and it shows a significant. Discussion: There are 2 potential mechanisms by which High – Frequency TENS can relieve the pain of diabetic neuropathy. It is possible that TENS alleviates pain by directly blocking abnormal spontaneous activity in small diameter pain mediating peripheral nerves. This mechanism requires electrical stimulation to be applied directly to spontaneously active nerve. In addition TENS can relieve the pain of diabetic neuropathy by altering nociceptive transmission in the dorsal horn of spinal cord. The second mechanism requires that stimulation be delivered to spinal cord segments that

  13. Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.

    Science.gov (United States)

    Jolivalt, C G; Calcutt, N A; Masliah, E

    2012-01-27

    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.

  14. Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

    Science.gov (United States)

    Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

    2015-05-01

    Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.

  15. Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Stuti L. Misra

    2014-01-01

    Full Text Available Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P=0.12 and P=0.33, resp.. Tear lipid thickness (P=0.02, stability (P<0.0001, and quantity (P=0.01 were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P<0.001 and tear film stability was inversely associated with total neuropathy score (r=-0.29, P=0.03. Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

  16. Treatment of diabetic neuropathy in the lower limb

    African Journals Online (AJOL)

    Muscular pain secondary to injury to the motor neurons can present as night cramps, spasm or a dull ache. Motor signs and ... al., in the UK neuropathy study, showed that patients in the 20 -. 29-year age group had .... Acupuncture. Traditional ...

  17. Effects of vibrating insoles on standing balance in diabetic neuropathy

    NARCIS (Netherlands)

    Hijmans, Juha M.; Geertzen, Jan H. B.; Zijlstra, Wiebren; Hof, At L.; Postema, Klaas

    2008-01-01

    This study investigated the effects on standing balance of random vibrations applied to the plantar side of the feet by vibrating insoles in subjects with neuropathy and nondisabled subjects. In four different conditions (eyes open or closed and with or without an attention-demanding task [ATD]), su

  18. Human beta-mannosidase deficiency associated with peripheral neuropathy.

    Science.gov (United States)

    Levade, T; Graber, D; Flurin, V; Delisle, M B; Pieraggi, M T; Testut, M F; Carrière, J P; Salvayre, R

    1994-01-01

    Human beta-mannosidosis is an inherited lysosomal storage disorder described in only seven families. We present a further case in a black African 14-year-old boy with severely deficient beta-mannosidase activity, bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The clinical and biochemical features of our patient are compared to those of previously reported patients.

  19. Treatment of diabetes mellitus-associated neuropathy with vitamin E and Eve primrose

    Directory of Open Access Journals (Sweden)

    Anthonia Okeoghene Ogbera

    2014-01-01

    Full Text Available Background: The aim of this report was to assess the efficacy and safety of a combination of vitamin E, an antioxidant, and Eve Primrose in the management of painful diabetes mellitus (DM neuropathy. Materials and Methods: This was an interventional study that evaluated the efficacy and safety of a combination of vitamin E and Eve Primrose in the management of DM neuropathy. The study was conducted at the Diabetic Centre of the Lagos State University Teaching Hospital, Ikeja. Eighty individuals with type 2 DM who had painful neuropathy were recruited for this study, which took place for a duration of 1 year. The study subjects underwent clinical and biochemical assessment at baseline and were given vitamin E in a dose of 400 mg in combination with Eve Primrose in doses ranging 500-1000 mg/day. They were afterward assessed for relief of symptoms and possible untoward effects after 2 weeks and, thereafter, monthly for 3 months. The main outcome measure was amelioration of symptoms of neuropathy . Results: The mean age and age range of the study subjects were 58.2 years and 37-70 years, respectively. A total of 70 patients (88% of the study population reported relief from neuropathic pains. Clinical parameters were comparable between the responders and non-responders. One characteristic feature of the non-responders was that they all had vibration perception threshold of ≥25 mV, which was indicative of severe neuropathy. Conclusion: The combination of vitamin E and Eve Primrose is beneficial in the management of mild to moderate diabetic neuropathy.

  20. Evolving Insights into the Pathophysiology of Diabetic Neuropathy: Implications of Malfunctioning Glia and Discovery of Novel Therapeutic Targets.

    Science.gov (United States)

    Rahman, Md Habibur; Jha, Mithilesh Kumar; Suk, Kyoungho

    2016-01-01

    Diabetic neuropathy subsequent to chronic high blood glucose-induced nerve damage is one of the most frustrating and debilitating complications of diabetes, which affects the quality of life in patients with diabetes. Approximately 60-70% of patients with diabetes suffer from a distal symmetrical form of mild to severe neuropathy that progresses in a fiber-length-dependent pattern, with sensory and autonomic manifestations predominating. High glucose and oxidative stress-mediated damage in neurons and glial cells, as well as neuroinflammation and crosstalk between these disease processes, have garnered immense attention as the essential mechanisms underlying the development and progression of diabetic neuropathy. Although the metabolic causes of diabetic neuropathy are well understood and documented, treatment options for this disorder are still limited, highlighting the need for further studies to identify new molecular and therapeutic targets. This review covers recent advances in our knowledge of the pathophysiology of diabetic neuropathy, discusses how persistent hyperglycemic conditions and malfunctioning glia drive disease progression, and finally explores the possibilities and challenges offered by several potential novel therapeutic targets for both preventing and reversing diabetic neuropathy.

  1. Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Georgios Ponirakis

    2015-01-01

    Full Text Available Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics outputs to diagnose diabetic peripheral neuropathy (DPN. 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS, peroneal motor nerve conduction velocity (PMNCV, sural nerve action potential (SNAP, Deep Breathing-Heart Rate Variability (DB-HRV, intraepidermal nerve fibre density (IENFD, and corneal confocal microscopy (CCM. 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%, CNFD (88%, 78%, and SNAP (88%, 83%, whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV and 80% for small fibre neuropathy (CNFD. The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P=0.0003 and CNFD (AUC: 82%, P=0.01 was better than for PMNCV (AUC: 60%. The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.

  2. Guaifenesin derivatives promote neurite outgrowth and protect diabetic mice from neuropathy.

    Science.gov (United States)

    Hadimani, Mallinath B; Purohit, Meena K; Vanampally, Chandrashaker; Van der Ploeg, Randy; Arballo, Victor; Morrow, Dwane; Frizzi, Katie E; Calcutt, Nigel A; Fernyhough, Paul; Kotra, Lakshmi P

    2013-06-27

    In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy.

  3. [Detection and treatment of lower extremity neuropathy in patients with diabetic foot].

    Science.gov (United States)

    Kucherenko, N V; Skrypova, T V; Liutkevych, V F; Turans'kyĭ, A I; Skybun, V M

    2001-08-01

    Possibilities of diagnosis and treatment of the lower extremities neuropathy were studied in 118 patients with diabetes mellitus (DM). Neurological examination, investigation of algesic, vibratory and temperature sensibility, thermography of feet were done in each patient. Electrostimulation treatment using therapeutic-diagnostic complex "Salut 11" was applied in 47 patients. Algesic syndrome and paresthesia occurs in the absence of the ulcerative-necrotic changes of foot or together with disorders of passability of the lower extremity main arteries. Ulcerative-necrotic changes of the foot tissues, caused by diabetic microangiopathy, are observed in the absence of pain and paresthesia, witnessing the presence of various mechanisms of the diabetic neuropathy occurrence. Application of the alpha-lipoic acid preparations had promoted the reduction of the pain and paresthesia intensity in 63% of patients. Usage of the lower extremities electromyoneurostimulation with the help of permanent impulsive current promotes the healing improvement of the purulent-necrotic wounds and ulcers of foot in patients with DM.

  4. Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

    DEFF Research Database (Denmark)

    Christensen, Tomas M; Simonsen, Lene; Holstein, Per E

    2011-01-01

    AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest...... was the patients with acute Charcot foot (n=17) or chronic Charcot foot (n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients...... with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic...

  5. Cardiovascular, metabolic, and hormonal responses to noradrenaline in diabetic patients with autonomic neuropathy

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Andersen, P; Hvidberg, A

    1996-01-01

    Denervation hypersensitivity is a well-known phenomenon in patients with autonomic failure. In diabetic autonomic neuropathy hypersensitivity to beta-adrenergic stimulation has been demonstrated. We infused noradrenaline, mainly an alpha-adrenoceptor agonist, in three escalating doses (0.5, 2.......5, and 5 micrograms min-1) in three age and sex matched groups of eight subjects: healthy volunteers, diabetic patients with and without autonomic neuropathy. During steady state in each infusion period we measured heart rate, blood pressure, cardiac output, hepato-splanchnic blood flow, vascular...... resistance, glucose kinetics, metabolites (beta-hydroxybuturate, glycerol, and lactate), and glucoregulatory hormones (noradrenaline, adrenaline, growth hormone, pancreatic polypeptide, cortisol, and insulin). Systolic and mean blood pressure increased in all groups but diabetic patients with autonomic...

  6. Low Intensity Laser Therapy (LILT) Versus Transcutaneous Electrical Nerve Stimulation On Microcirculation In Diabetic Neuropathy

    Science.gov (United States)

    Battecha, Kadria H.; Atya, Azza M.

    2011-09-01

    Reduced microcirculation is a morbid element of neuropathy and one of the most common complications of uncontrolled diabetes. Many physical modalities have gained a considerable attention for enhancing cutaneous microcirculation in diabetic patients and prevent its serious complications. Accordingly, the present study was conducted to compare between the effect of low intensity laser therapy (LILT) and transcutaneous electrical nerve stimulation (TENS) on microcirculation in diabetic neuropathy. Thirty diabetic polyneuropathic patients ranged in age from 45-60 years participated in this study. They were randomly divided into two groups of equal number; patients in group (A) received LILT on plantar surface of foot with a dose of 3 J/cm2 and wavelength (904 nm), while those in group (B) received TENS on lower leg for 30 minutes with frequency (2 HZ). Treatment was conducted 3 times/week for 6 weeks. The cutaneous microcirculation was evaluated by Laser Doppler flowmetry at the baseline and at the end of treatment. Results revealed that group (A) showed statistically significant increase in the cutaneous microcirculation compared with group (B). So, it was concluded that LILT has to be more efficient than TENS in increasing cutaneous microcirculation in patients with diabetic neuropathy.

  7. Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy.

    Science.gov (United States)

    Koneri, Raju B; Samaddar, Suman; Simi, S M; Rao, Srinivas T

    2014-01-01

    To investigate the neuroprotective potential of a saponin isolated from the roots of Momordica cymbalaria against peripheral neuropathy in streptozotocin-induced diabetic rats. A steroidal saponin (SMC) was isolated from M. cymbalaria Fenzl and purified by preparative high-performance liquid chromatography. Diabetes was induced in male Wister rats by injecting streptozotocin 45 mg/kg. Diabetic rats were divided into six groups for neuroprotective effect--three each for preventive and curative groups. Neuropathic analgesia was assessed by tail-flick and hot-plate methods. Dorsal root ganglion (DRG) neurons and sciatic nerves were isolated, and histopathological analysis was performed. Antioxidant activity (superoxide dismutase, catalase, and inhibition of lipid peroxidation) of the saponin was also carried out on the isolated DRG neurons and sciatic nerves to assess total oxidative stress. In both preventive and curative protocols, rats administered with SMC showed significant decrease in tail immersion latency time and increase in pain sensitivity when compared to diabetic control group. There was improvement in the myelination and degenerative changes of the nerve fiber in both the groups, and an obvious delay in the progression of neuropathy was evident. SMC treatment showed significant decrease in superoxide dismutase, catalase activity, and lipid peroxidation in the nerves. The steroidal saponin of M. cymbalaria (SMC) possesses potential neuroprotective effect in diabetic peripheral neuropathy with respect to neuropathic analgesia, improvement in neuronal degenerative changes, and significant antioxidant activity.

  8. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    A K Singh

    2013-01-01

    Full Text Available Context: Long-term metformin use has been hypothesized to cause B12 deficiency and neuropathy in Type 2 diabetes patients. However, there is a paucity of Indian data regarding the same. Aim: To compare the prevalence of B12 deficiency and peripheral neuropathy in patients with Type 2 diabetes mellitus treated with or without metformin. Materials and Methods: We recruited patients with Type 2 diabetes and divided them into metformin exposed and nonmetformin exposed groups. We measured baseline demographic variables like age, sex, vegetarian status, and HbA1c levels in both groups. We compared vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS in both groups. Definite B12 deficiency was defined as B12 <150 pg/ml and possible B12 deficiency as <220 pg/ml. The difference in vitamin B12 levels and TCSS was calculated in both groups using independent samples t-test. Spearman′s rank correlation between cumulative metformin use and B12 level was calculated. Odds ratio of vitamin B12 deficiency in metformin exposed group was also estimated. Results: Mean serum B12 levels was significantly lower in metformin exposed group (n=84 compared with nonmetformin exposed group (n=52 (410±230.7 versus 549.2±244.7, P=0.0011. Mean neuropathy score was significantly higher in metformin exposed group. (5.72±2.04 versus 4.62±2.12, P=0.0064. Odds ratio for possible B12 deficiency was 4.45 (95% CI 1.24-15.97. There was significant negative correlation between cumulative metformin dose and vitamin B12 level (r=−0.68, P<0.0001. Conclusion: Metformin use is associated with vitamin B12 deficiency and clinical neuropathy in Type 2 diabetes patients.

  9. Is the C677T polymorphism in methylenetetrahydrofolate reductase gene or plasma homocysteine a risk factor for diabetic peripheral neuropathy in Chinese individuals?

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Dongsheng Fan; Tianpei Hong

    2012-01-01

    The present study enrolled 251 diabetic patients,including 101 with neuropathy and 150 without neuropathy.Of the 150 patients,100 had no complications,such as retinopathy,nephropathy,or neuropathy.Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants.Plasma homocysteine levels were also measured.Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy (P < 0.05).In logistic regression analysis with neuropathy as the dependent variable,the frequency of C677T in methylenetetrahydrofolate reductase was significantly higher in patients with diabetic peripheral neuropathy compared with patients without diabetic complications.Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels.In conclusion,hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes.The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.

  10. The role of autonomic cardiovascular neuropathy in pathogenesis of ischemic heart disease in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Popović-Pejičić Snježana

    2006-01-01

    Full Text Available Introduction. Diabetes is strongly associated with macrovascular complications, among which ischemic heart disease is the major cause of mortality. Autonomic neuropathy increases the risk of complications, which calls for an early diagnosis. The aim of this study was to determine both presence and extent of cardiac autonomic neuropathy, in regard to the type of diabetes mellitus, as well as its correlation with coronary disease and major cardiovascular risk factors. Material and methods. We have examined 90 subjects, classified into three groups, with 30 patients each: those with type 1 diabetes, type 2 diabetes and control group of healthy subjects. All patients underwent cardiovascular tests (Valsalva maneuver, deep breathing test, response to standing, blood pressure response to standing sustained, handgrip test, electrocardiogram, treadmill exercise test and filled out a questionnaire referring to major cardiovascular risk factors: smoking, obesity, hypertension, and dyslipidemia. Results. Our results showed that cardiovascular autonomic neuropathy was more frequent in type 2 diabetes, manifesting as autonomic neuropathy. In patients with autonomic neuropathy, regardless of the type of diabetes, the treadmill test was positive, i.e. strongly correlating with coronary disease. In regard to coronary disease risk factors, the most frequent correlation was found for obesity and hypertension. Discussion Cardiovascular autonomic neuropathy is considered to be the principal cause of arteriosclerosis and coronary disease. Our results showed that the occurrence of cardiovascular autonomic neuropathy increases the risk of coronary disease due to dysfunction of autonomic nervous system. Conclusions. Cardiovascular autonomic neuropathy is a common complication of diabetes that significantly correlates with coronary disease. Early diagnosis of cardiovascular autonomic neuropathy points to increased cardiovascular risk, providing a basis for preventive

  11. Xanthine Oxidase Activity in Type 2 Diabetes Mellitus Patients with and without Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Dijana J. Miric

    2016-01-01

    Full Text Available This study investigated the relationship between serum xanthine oxidase (XOD activity and the occurrence of diabetic peripheral neuropathy (DPN in type 2 diabetes mellitus (T2DM patients. Serum XOD activity, ischemia-modified albumin (IMA, uric acid (UA, albumin, glycated hemoglobin (HbA1c, advanced glycation end products (AGE, total free thiols, atherogenic index of plasma (AIP, and body mass index (BMI were measured in 80 T2DM patients (29 with and 51 without DPN, and 30 nondiabetic control subjects. Duration of diabetes, hypertension, medication, and microalbuminuria was recorded. Serum XOD activities in controls, non-DPN, and DPN were 5.7±2.4 U/L, 20.3±8.6 U/L, and 27.5±10.6 U/L (p<0.01, respectively. XOD activity was directly correlated to IMA, UA, BMI, HbA1c, and AGE, while inversely correlated to serum total free thiols. A multivariable logistic regression model, which included duration of diabetes, hypertension, AIP, HbA1c, UA, and XOD activity, revealed HbA1c [OR = 1.03 (1.00–1.05; p=0.034] and XOD activity [OR = 1.07 (1.00–1.14; p=0.036] as independent predictors of DPN. Serum XOD activity was well correlated to several other risk factors. These results indicate the role of XOD in the development of DPN among T2DM patients.

  12. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

    OpenAIRE

    Han-yu Dong; Xin-mei Jiang; Chun-bo Niu; Lin Du; Jun-yan Feng; Fei-yong Jia

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve...

  13. Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

    Science.gov (United States)

    Coppey, Lawrence J; Davidson, Eric P; Obrosov, Alexander; Yorek, Mark A

    2015-02-01

    The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

  14. Calpain inhibitor, MDL 28170 confer electrophysiological, nociceptive and biochemical improvement in diabetic neuropathy.

    Science.gov (United States)

    Kharatmal, Shivsharan B; Singh, Jitendra N; Sharma, Shyam S

    2015-10-01

    Calpain plays an important role in the pathophysiology of neurological and cardiovascular complications, but its functional association in diabetic neuropathy is not yet elucidated. Therefore, we investigated the role of calpain in modulation of tetrodotoxin-resistant sodium channels (TTX-R Na(+) channels) in dorsal root ganglion (DRG) neurons using a pharmacological approach. The effects of a calpain inhibitor, MDL 28170 (3 and 10 mg/kg, i.p.) on TTX-R Na(+) channels in DRG neurons of streptozotocin-induced diabetic rats were assessed by using whole-cell patch-clamp technique. In addition to this biochemical, functional and behavioral deficits were also measured. Diabetic rats demonstrated the mechanical allodynia and thermal hyperalgesia with reduced nerve perfusion and conduction velocity as compared to control. MDL 28170 treatments significantly recovered these functional and nociceptive deficits. Moreover, diabetic rats exhibited increased calpain activation, lipid peroxidation and proinflammatory cytokines as compared to control. Drug treatment significantly improved these biochemical deficits. Additionally, DRG neurons from diabetic rats illustrated a significant increase in TTX-R sodium current (INa) density as compared to control. MDL 28170 treatments in diabetic rats significantly blocked the altered channel kinetics with hyperpolarizing shift in voltage-dependence of steady-state activation and inactivation curves. All together, our study provides evidence that calpain activation is directly associated with alterations in TTX-R Na(+) channels and triggers functional, nociceptive and biochemical deficits in experimental diabetic neuropathy. The calpain inhibitor, MDL 28710 have shown beneficial effects in alleviating diabetic neuropathy via modulation of TTX-R Na(+) channel kinetics and reduction of oxidative stress and neuro-inflammation.

  15. Verrucous lesions arising in lymphedema and diabetic neuropathy: Elephantiasis nostras verrucosa or verrucous skin lesions on the feet of patients with diabetic neuropathy?

    Science.gov (United States)

    Hotta, Eri; Asai, Jun; Okuzawa, Yasutaro; Hanada, Keiji; Nomiyama, Tomoko; Takenaka, Hideya; Katoh, Norito

    2016-03-01

    Verrucous skin lesions on the feet in diabetic neuropathy (VSLDN) develop in areas with sensory loss in diabetic patients. Although various types of chronic stimulation, such as pressure or friction, are considered an important factor in the development of such lesions, the precise pathogenesis of VSLDN remains obscure, and there is currently no established treatment for this disease. Here, we present a case of VSLDN on the dorsum of the right foot. However, because lymphedema was also observed at the same site, this lesion could also be diagnosed as elephantiasis nostras verrucosa arising in diabetic neuropathy. The lesion was successfully treated with a combination of elastic stocking and mixed killed bacterial suspension and hydrocortisone ointment, which suggested that VSLDN might have been exacerbated by the pre-existing lymphedema. Because various types of chronic stimulation can trigger VSLDN, treatment plans should be devised on a case-by-case basis. Therefore, it is important to investigate the presence of factors that can induce or exacerbate chronic inflammatory stimulation, such as lymphedema in our case, in each patient with VSLDN. © 2015 Japanese Dermatological Association.

  16. Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats.

    Science.gov (United States)

    Tian, Ruifeng; Yang, Wenqing; Xue, Qiang; Gao, Liang; Huo, Junli; Ren, Dongqing; Chen, Xiaoyan

    2016-01-15

    Rutin exhibits antidiabetic, antioxidant and anti-inflammatory properties, which makes rutin an attractive candidate for diabetic complications. The present study was designed to investigate the potential effect of rutin on diabetic neuropathy. After induction of diabetic neuropathy, rutin (5mg/kg, 25mg/kg and 50mg/kg) were daily given to the diabetic rats for 2 weeks. At the end of rutin administration, rutin produced a significant inhibition of mechanical hyperalgesia, thermal hyperalgesia and cold allodynia, as well as partial restoration of nerve conduction velocities in diabetic rats. Furthermore, rutin significantly increased Na(+), K(+)-ATPase activities in sciatic nerves and decreased caspase-3 expression in dorsal root ganglions (DRG). In addition, rutin significantly decreased plasma glucose, attenuated oxidative stress and neuroinflammation. Further studies showed that rutin significantly increased hydrogen sulfide (H2S) level, up-regulated the expression of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in DRG. The evidences suggest the beneficial effect of rutin on diabetic neuropathy. Additionally, insulin (2 IU) and BG-12 (15mg/kg) were used to investigate the mechanisms underlying the beneficial effect of rutin on diabetic neuropathy. Insulin achieved lower plasma glucose and BG-12 achieved comparable Nrf2 expression than/to rutin (50mg/kg), respectively. In contrast, the beneficial effect of insulin and BG-12 was inferior to that of rutin (50mg/kg), suggesting that both lowered plasma glucose and Nrf2 signaling contribute to the beneficial effect of rutin on diabetic neuropathy. In conclusion, rutin produces significant protection in diabetic neuropathy, which makes it an attractive candidate for the treatment of diabetic neuropathy.

  17. Contributory factors to unsteadiness during walking up and down stairs in patients with diabetic peripheral neuropathy.

    Science.gov (United States)

    Handsaker, Joseph C; Brown, Steven J; Bowling, Frank L; Cooper, Glen; Maganaris, Constantinos N; Boulton, Andrew J M; Reeves, Neil D

    2014-11-01

    Although patients with diabetic peripheral neuropathy (DPN) are more likely to fall than age-matched controls, the underlying causative factors are not yet fully understood. This study examines the effects of diabetes and neuropathy on strength generation and muscle activation patterns during walking up and down stairs, with implications for fall risk. Sixty-three participants (21 patients with DPN, 21 diabetic controls, and 21 healthy controls) were examined while walking up and down a custom-built staircase. The speed of strength generation at the ankle and knee and muscle activation patterns of the ankle and knee extensor muscles were analyzed. Patients with neuropathy displayed significantly slower ankle and knee strength generation than healthy controls during stair ascent and descent (P walking up and down stairs. These changes, which are likely caused by altered activations of the extensor muscles, increase the likelihood of instability and may be important contributory factors for the increased risk of falling. Resistance exercise training may be a potential clinical intervention for improving these aspects and thereby potentially reducing fall risk. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  18. Cardiovascular autonomic neuropathy contributes to sleep apnea in young and lean Type 1 Diabetes Mellitus patients

    Directory of Open Access Journals (Sweden)

    Carolina Castro Porto Silva Janovsky

    2014-08-01

    Full Text Available Sleep apnea in type 1 diabetes mellitus (T1DM is a crescent theme of discussion. In obese patient, it is explained by the excessive central adiposity, including large neck circumference. Its presence in nonobese patients, however, brings back its possible correlation with autonomic neuropathy. The aim of this study was to compare the prevalence of OSA in young and lean T1DM, with and without cardiovascular autonomic neuropathy (CAN. We studied 20 adult, nonobese, type 1 diabetic patients, divided in two groups according to the results of the cardiovascular autonomic reflex tests (CARTs. These two groups (9 with CAN and 11 without CAN were compared to a control group of 22 healthy individuals, matched by age and BMI. A polysomnography was performed and sleep was analyzed. The CAN+ group presented significantly higher prevalence of sleep apnea compared to the other groups (67% CAN+; 23% CAN-; 4,5% controls: CAN+ vs Control; p=0.00017 and CAN+ vs CAN-; p=0.02. As it was expected, the incidence of sleep apnea was correlated with more microarousals during sleep and excessive daytime sleepiness. The CAN- group showed a better sleep efficiency compared to the CAN+ group, demonstrating impaired sleep architecture in diabetics with this chronic complication. In conclusion, sleep apnea could not only be an indication of presence of CAN, but also a contributor to diabetic neuropathy impairment, causing both worse prognosis and reduced quality of life for these patients when not treated.

  19. Usefulness of myocardial imaging by [sup 123]I-MIBG in assessment of diabetic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Katono, Eiichi; Owada, Kenji; Takeda, Hiroto; Techigawara, Masa-aki (Ohta Nishinouchi Hospital, Koriyama, Fukushima (Japan)); Watanabe, Naohiko; Maruyama, Yukio

    1993-10-01

    In diabetic patients with autonomic neuropathy, it is suggested that there is a reduced uptake of [sup 123]I-metaiodobenzylguanidine (MIBG) in the heart. We compared the difference of myocardial [sup 123]I-MIBG accumulation between 4 diabetic patients with triopathy and 6 patients without it. In all 10 patients, coronary angiography and [sup 201]Tl imaging (rest and 4 hours later) were performed. [sup 123]I-MIBG (111 MBq) was administered intravenously and its imaging was recorded on 15 minutes and 4 hours after injection. In all 4 cases with triopathy, [sup 123]I-MIBG imaging showed defect in apical and inferior region. In 2 out of 6 cases without triopathy, rapid clearance was noticed in apical and inferior region. There was no significant stenosis in right coronary artery and no defect in initial and delayed [sup 201]Tl images in all cases. We concluded that diabetic autonomic neuropathy in the heart was prominent in apical and inferior region and [sup 123]I-MIBG imaging might be useful for the evaluation of degrees in diabetic neuropathy. (author).

  20. The role of foot morphology on foot function in diabetic subjects with or without neuropathy.

    Science.gov (United States)

    Guiotto, Annamaria; Sawacha, Zimi; Guarneri, Gabriella; Cristoferi, Giuseppe; Avogaro, Angelo; Cobelli, Claudio

    2013-04-01

    The aim of this study was to investigate the role of foot morphology, related with respect to diabetes and peripheral neuropathy in altering foot kinematics and plantar pressure during gait. Healthy and diabetic subjects with or without neuropathy with different foot types were analyzed. Three dimensional multisegment foot kinematics and plantar pressures were assessed on 120 feet: 40 feet (24 cavus, 20 with valgus heel and 11 with hallux valgus) in the control group, 80 feet in the diabetic (25 cavus 13 with valgus heel and 13 with hallux valgus) and the neuropathic groups (28 cavus, 24 with valgus heel and 18 with hallux valgus). Subjects were classified according to their foot morphology allowing further comparisons among the subgroups with the same foot morphology. When comparing neuropathic subjects with cavus foot, valgus heel with controls with the same foot morphology, important differences were noticed: increased dorsiflexion and peak plantar pressure on the forefoot (Pfoot morphology in altering both kinematics and plantar pressure in diabetic subjects, diabetes appeared to further contribute in altering foot biomechanics. Surprisingly, all the diabetic subjects with normal foot arch or with valgus hallux were no more likely to display significant differences in biomechanics parameters than controls. This data could be considered a valuable support for future research on diabetic foot function, and in planning preventive interventions.

  1. Classification of the severity of diabetic neuropathy: a new approach taking uncertainties into account using fuzzy logic

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    Andreja P. Picon

    2012-01-01

    Full Text Available OBJECTIVE: This study proposes a new approach that considers uncertainty in predicting and quantifying the presence and severity of diabetic peripheral neuropathy. METHODS: A rule-based fuzzy expert system was designed by four experts in diabetic neuropathy. The model variables were used to classify neuropathy in diabetic patients, defining it as mild, moderate, or severe. System performance was evaluated by means of the Kappa agreement measure, comparing the results of the model with those generated by the experts in an assessment of 50 patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50 other cases; the results of those clinical assessments were considered to be the gold standard. RESULTS: According to the Kappa analysis, the model was in moderate agreement with expert opinions. The ROC analysis (evaluation of accuracy determined an area under the curve equal to 0.91, demonstrating very good consistency in classifying patients with diabetic neuropathy. CONCLUSION: The model efficiently classified diabetic patients with different degrees of neuropathy severity. In addition, the model provides a way to quantify diabetic neuropathy severity and allows a more accurate patient condition assessment.

  2. Classification of the severity of diabetic neuropathy: a new approach taking uncertainties into account using fuzzy logic

    Science.gov (United States)

    Picon, Andreja P; Ortega, Neli R S; Watari, Ricky; Sartor, Cristina; Sacco, Isabel C N

    2012-01-01

    OBJECTIVE: This study proposes a new approach that considers uncertainty in predicting and quantifying the presence and severity of diabetic peripheral neuropathy. METHODS: A rule-based fuzzy expert system was designed by four experts in diabetic neuropathy. The model variables were used to classify neuropathy in diabetic patients, defining it as mild, moderate, or severe. System performance was evaluated by means of the Kappa agreement measure, comparing the results of the model with those generated by the experts in an assessment of 50 patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50 other cases; the results of those clinical assessments were considered to be the gold standard. RESULTS: According to the Kappa analysis, the model was in moderate agreement with expert opinions. The ROC analysis (evaluation of accuracy) determined an area under the curve equal to 0.91, demonstrating very good consistency in classifying patients with diabetic neuropathy. CONCLUSION: The model efficiently classified diabetic patients with different degrees of neuropathy severity. In addition, the model provides a way to quantify diabetic neuropathy severity and allows a more accurate patient condition assessment. PMID:22358240

  3. Autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1980-01-01

    In order to elucidate the physiological significance of autonomic neuropathy in juvenile diabetics, cardiovascular, hormonal and metabolic functions have been investigated in three groups of juvenile diabetics: One group had no signs of neuropathy, one group had presumably slight autonomic...... neuropathy (reduced beat-to-beat variation in heart rate during hyperventilation) and one group had clinically severe autonomic neuropathy, defined by presence of orthostatic hypotension. In all three experimental situations we found sympathetic dysfunction causing cardiovascular and/or hormonal...... maladjustments in patients with autonomic neuropathy. Regarding metabolic functions we found normal responses to graded exercise and insulin-induced hypoglycemia in patients with autonomic neuropathy in spite of blunted catecholamine responses, suggesting increased sensitivity of glycogen stores and adipose...

  4. Plasma adrenaline kinetics in type 1 (insulin-dependent) diabetic patients with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Hilsted, J; Henriksen, J H

    1989-01-01

    Plasma adrenaline kinetics (clearance, extraction across the forearm, initial plasma disappearance rate, mean sojourn time, volume of distribution) were studied in sixteen Type 1 (insulin-dependent) diabetic patients during constant i.v. infusion of tritium labelled adrenaline. In patients with (n...... = 8) and without (n = 8) neuropathy forearm venous plasma noradrenaline and adrenaline concentrations as well as plasma clearance of adrenaline based on arterial sampling (1.7 vs 2.1 l/min) were not significantly different. The initial disappearance time (T 1/2) after the infusion of the tritium...... labelled adrenaline had been stopped was significantly prolonged in Type 1 diabetic patients with neuropathy compared to those without (after 20 min infusion 2.7 vs 2.2 min, p less than 0.02, after 75 min infusion 3.7 vs 2.9 min, p less than 0.05). The corresponding values for the mean sojourn time...

  5. Magnetic resonance imaging of the central nervous system in diabetic neuropathy.

    Science.gov (United States)

    Wilkinson, Iain D; Selvarajah, Dinesh; Greig, Marni; Shillo, Pallai; Boland, Elaine; Gandhi, Rajiv; Tesfaye, Solomon

    2013-08-01

    Diabetic 'peripheral' neuropathy (DPN) is one of the common sequelae to the development of both type-1 and type-2 diabetes mellitus. Neuropathy has a major negative impact on quality of life. Abnormalities in both peripheral vasculature and nerve function are well documented and, in addition, evidence is emerging regarding changes within the central nervous system (CNS) that are concomitant with the presence of DPN. The often-resistant nature of DPN to medical treatment highlights the need to understand the role of the CNS in neuropathic symptomatology and progression, as this may modulate therapeutic approaches. Advanced neuroimaging techniques, especially those that can provide quantitative measures of structure and function, can provide objective markers of CNS status. With that comes great potential for not only furthering our understanding of involvement of the CNS in neuropathic etiology but also most importantly aiding the development of new and more effective, targeted, analgesic interventions.

  6. Clinical Study of Jinmaitong Composita(复方筋脉通) on Diabetic Peripheral Neuropathy

    Institute of Scientific and Technical Information of China (English)

    梁晓春; 崔丽英; 郭赛珊; 张克俭; 郝炜欣; 贾力; 张宏; 孙仁宇; 李本红; 杜红

    2001-01-01

    Objective: To verify the effect of Jinmaitong composita (JMTC) on red blood cell aldose reductase activity (RBC-AR), red blood cell sorbitol (RBC-S) and nerve conductive velocity in diabetic peripheral neuropathy (DN) patients. Methods: Sixty-six patients with DN were randomly divided into two groups, 33 patients in the treated group treated with JMTC and 33 patients in the control group treated with Jingui Shenqi capsule (JGSQ). RBC-AR, RBC-S and nerve transmission speed were observed before and after three months treatment.Results: Level of RBC-AR, RBC-S apparently decreased and nerve conductive velocity increased (P<0.05, P<0.01) after JMTC treatment.Conclusion: JMTC can improve the nerve conductive velocity significantly with a lowering of RBC-AR and RBC-S and has a good result in treating diabetic peripheral neuropathy.

  7. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

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    Han-yu Dong

    2016-01-01

    Full Text Available To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position, prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds, and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

  8. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy.

    Science.gov (United States)

    Dong, Han-Yu; Jiang, Xin-Mei; Niu, Chun-Bo; Du, Lin; Feng, Jun-Yan; Jia, Fei-Yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

  9. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Han-yu Dong; Xin-mei Jiang; Chun-bo Niu; Lin Du; Jun-yan Feng; Fei-yong Jia

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

  10. Manual Acupuncture for Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Controlled Trials

    OpenAIRE

    Wei Chen; Guo-Yan Yang; Bo Liu; Eric Manheimer; Jian-Ping Liu

    2013-01-01

    OBJECTIVE: Manual acupuncture has commonly been used in China, either alone or in combination with conventional medicine, to treat diabetic peripheral neuropathy (DPN). The objective of this study was to perform a systematic review to evaluate the potential benefits and harms of manual acupuncture for DPN to justify its clinical use. METHODS: We searched for published and unpublished randomized controlled trials of manual acupuncture for DPN till 31 March 2013. Revman 5.2 software was used fo...

  11. THE BENEFICIAL EFFECT OF ASIATICOSIDE ON EXPERIMENTAL NEUROPATHY IN DIABETIC RATS

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    Chonlathip Thipkaew

    2012-01-01

    Full Text Available Though diabetic neuropathy produces high impact on quality of life, annual cost and morbidities, the therapeutic efficacy is still not in a satisfaction level. Based on the crucial role of oxidative stress on the pathophysiology of diabetic neuropathy and the improvement of this condition induced by antioxidant, we hypothesized that asiaticoside, a substance possessing antioxidant activity, could provide beneficial effect. Therefore, we aimed to determine the effect of asiaticoside on the recovery of sciatic nerve in experimental neuropathy in diabetic rats. Young adult male Wistar rats at 8 weeks old, weighing approximate 180-220 g, were orally given asiaticoside at doses of 0.1 and 1 mg kg-1 BW at a period of 5 days before and 3 weeks after sciatic nerve crush injury. Motor and sensory functions were observed every 3 day until the end of the experiment by using Deminacelli method, walking pattern, muscle power and foot reflex withdrawal test, respectively. Our results showed that both doses of asiaticoside could significantly reverse the enhanced withdrawal threshold intensity elicited by electrical stimuli. However, the rats received asiaticoside at dose of 1 mg kg-1 BW provided optimum benefit. However, no other significant effects were observed. Asiaticoside administration in an experimental model of neuropathy in diabetic rats mitigates some functional impairment of sciatic nerve. Though our data show only the beneficial effect of asiaticoside on the foot withdrawal reflex, it is very much important because it involve the protective mechanism against painful stimuli. Therefore, it is worth for further investigation in order to confirm the improvement of sensori-motor functions and determined the both therapeutic window and possible underlying mechanism."

  12. Pseudohypertrophy of the calf muscles in a patient with diabetic neuropathy: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jin; Lee, Young Hwan; Jung, Kyung Jae; Park, Young Chan; Kim, Ho Kyun; Kim, Ok Dong [School of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)

    2007-09-15

    Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers.

  13. Electrochemical Skin Conductance May Be Used to Screen for Diabetic Cardiac Autonomic Neuropathy in a Chinese Population with Diabetes

    Science.gov (United States)

    He, Tianyi; Wang, Chuan; Zuo, Anju; Liu, Pan; Li, Wenjuan

    2017-01-01

    Aims. This study aimed to assess whether the electrochemical skin conductance (ESC) could be used to screen for diabetic cardiac autonomic neuropathy (DCAN) in a Chinese population with diabetes. Methods. We recruited 75 patients with type 2 diabetes mellitus (T2DM) and 45 controls without diabetes. DCAN was diagnosed by the cardiovascular autonomic reflex tests (CARTs) as gold standard. In all subjects ESCs of hands and feet were also detected by SUDOSCAN™ as a new screening method. The efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results. The ESCs of both hands and feet were significantly lower in T2DM patients with DCAN than those without DCAN (67.33 ± 15.37 versus 78.03 ± 13.73, P = 0.002, and 57.77 ± 20.99 versus 75.03 ± 11.41, P diabetes before further diagnosis with CARTs.

  14. Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient

    Directory of Open Access Journals (Sweden)

    David S. H. Bell

    2012-01-01

    Full Text Available Vitamin D deficiency has been associated with both type 1 and type 2 diabetes as well as both the microvascular and macrovascular complications of diabetes. Vitamin D deficiency has been shown to be more common in diabetic patients who have symptoms of distal symmetrical polyneuropathy. In addition, vitamin D deficiency has been associated with a lower pain threshold which increases when vitamin D deficiency is corrected. Herein, I describe a type 1 diabetic patient with neuropathic symptoms so severe that he could not work and for which he needed narcotics for pain management and whose symptoms improved dramatically with correction of the vitamin D deficiency. To my knowledge, this is the first report of an improvement in severe symptoms of diabetic neuropathy with correction of vitamin D deficiency in a single patient.

  15. MDCT assessment of CAD in type-2 diabetic subjects with diabetic neuropathy: the role of Charcot neuro-arthropathy.

    Science.gov (United States)

    Marano, Riccardo; Pitocco, Dario; Di Stasio, Enrico; Savino, Giancarlo; Merlino, Biagio; Trani, Carlo; Pirro, Federica; Rutigliano, Claudia; Santangelo, Carolina; Minoiu, Aurelian Costin; Natale, Luigi; Bonomo, Lorenzo

    2016-03-01

    To compare the CACS and CAD severity assessed by MDCT in neuropathic type-2 diabetic patients with and without Charcot-neuroarthropathy (CN). Thirty-four CN asymptomatic-patients and 36 asymptomatic-patients with diabetic-neuropathy (DN) without CN underwent MDCT to assess CACS and severity of CAD. Patients were classified as positive for significant CAD in presence of at least one stenosis >50 % on MDCT-coronary-angiography (MDCT-CA). Groups were matched for age, sex and traditional CAD risk-factors. The coronary-angiography (CA) was performed in all patients with at least a significant stenosis detected by MDCT-CA, both as reference and eventually as treatment. CN patients showed higher rates of significant CAD in comparison with DN subjects [p CAD of 87%. These preliminary data suggest that CN-patients have a higher prevalence of severe CAD in comparison with DN-patients, while coronary plaques do not exhibit an increased amount of calcium. MDCT may be helpful to assess the CV risk in such asymptomatic type-2-diabetic patients with autonomic-neuropathy. Type 2-diabetic-patients with CN result having more severe coronary artery plaque-burden. MDCT-CA may stratify the CV risk in type 2-diabetic-patients with CN. Adequate diagnostic is mandatory for optimal management of type 2-diabetic-patients with CN.

  16. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    Science.gov (United States)

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  17. Determination of efficacy of reflexology in managing patients with diabetic neuropathy: a randomized controlled clinical trial.

    Science.gov (United States)

    Dalal, Krishna; Maran, V Bharathi; Pandey, Ravindra M; Tripathi, Manjari

    2014-01-01

    Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N = 58) with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.

  18. Determination of Efficacy of Reflexology in Managing Patients with Diabetic Neuropathy: A Randomized Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Krishna Dalal

    2014-01-01

    Full Text Available Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N=58 with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.

  19. Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy.

    Science.gov (United States)

    Abbas, Z G; Swai, A B

    1997-12-01

    The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy. Of 200 consecutive patients, 100 were randomly allocated to treatment with both thiamine (25 mg/day) and pyridoxine (50 mg/day) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine. Pain, numbness, paraesthesia and impairment of sensation and ankle in the legs were graded into none, mild, moderate or severe. Blood thiamine levels were measured using HPLC fluorimetry. Four weeks after starting treatment the grade was less than on the first visit in 88.9%, 82.5% and 89.7% of those whose worst symptoms were pain, numbness and paraesthesia respectively for group A compared with 11.1%, 40.5% and 39.4% respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9% of patients in group A compared with 11.4% in group B. The mean (s.e.) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms: 64.2 (2.81), 57.7 (3.25) and 52.2 (2.14) micrograms/l for those with mild, moderate and severe symptoms respectively (analysis of variance, p = 0.03). Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency. Dietary guidelines for diabetic patients should emphasize a balanced diet.

  20. Inverse association between serum total bilirubin levels and diabetic peripheral neuropathy in patients with type 2 diabetes.

    Science.gov (United States)

    Kim, Eun Sook; Lee, Sung Won; Mo, Eun Young; Moon, Sung Dae; Han, Je Ho

    2015-11-01

    Several studies have suggested that bilirubin, a potent innate antioxidant, plays a protective role against cardiovascular and microvascular disease. This study investigated the association between serum concentrations of total bilirubin (TB) and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic patients. This cross-sectional study involved 1207 patients aged more than 30 years with type 2 diabetes. DPN was assessed according to clinical symptoms and physical examinations using Michigan Neuropathy Screening Instrument examination score, 10-g monofilament sensation, and current perception threshold. The subjects were stratified into gender-specific tertiles based on TB values, and the relationship between the TB values and DPN was analyzed. Compared with patients within the lowest TB tertile, those with higher TB levels consisted of patients with shorter duration of diabetes, lower HbA1c, better renal function, and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were inversely associated with DPN. In multivariate analysis for the development of DPN after adjusting for potential confounding factors including retinopathy, albuminuria, and autonomic neuropathy, the TB levels were inversely associated with the presence of DPN, both as a continuous variable [odds ratio (OR) per log standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022] and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63; 95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly associated with DPN, independently of classic risk factors and other microvascular complications. Further investigation is necessary to determine whether serum bilirubin has a prognostic significance on DPN.

  1. Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ariga Toshio

    2007-11-01

    Full Text Available Abstract Background To study the effects of a pre-germinated brown rice diet (PR on diabetic neuropathy in streptozotocin (STZ-induced diabetic rats. Methods The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR or white rice (WR diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV, sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase activity. Results Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p +/K+-ATPase activity (1.6- and 1.7-fold higher, respectively. The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p in vitro effect of the total lipid extract from PR bran (TLp on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT with low-density lipoprotein (LDL in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL. Conclusion PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the sciatic-nerve membrane from the toxicity of HT-modified LDL and to directly

  2. Increased axonal regeneration and swellings in intraepidermal nerve fibers characterize painful phenotypes of diabetic neuropathy

    OpenAIRE

    Cheng, H.T.; Dauch, J.R.; Porzio, M.T.; Yanik, B.M.; Hsieh, W; Smith, A.G.; Singleton, J.R.; Feldman, E.L.

    2013-01-01

    We examined changes in intraepidermal nerve fibers (IENFs) to differentiate patients with diabetic neuropathy (DN) and neuropathic pain (DN-P) from those with DN without pain (DN-NOP). Punch skin biopsies were collected from the proximal thigh (PT) and distal leg (DL) of normal subjects (NS), patients with type 2 diabetes without evidence of DN (DM), or DN-P and DN-NOP patients. Protein gene product 9.5 (PGP) immunohistochemistry was used to quantify total IENF, and growth associated protein ...

  3. Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy.

    Science.gov (United States)

    Ascaso, J F; Herreros, B; Sanchiz, V; Lluch, I; Real, J T; Minguez, M; Mora, F; Benages, A

    2006-09-01

    The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P 10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P 10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.

  4. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

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    Ahmet Kaya

    2016-03-01

    Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.

  5. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

    Directory of Open Access Journals (Sweden)

    Tobias Wienemann

    2014-11-01

    Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

  6. Effect of flat insoles with different Shore A values on posture stability in diabetic neuropathy.

    Science.gov (United States)

    Van Geffen, J A; Dijkstra, P U; Hof, A L; Halbertsma, J P K; Postema, K

    2007-09-01

    The objective of the study was to determine whether insoles with a low Shore A value (15 degrees) as prescribed for patients with a diabetic neuropathy have a negative effect on posture stability because these insoles may reduce somatosensory input under the feet. It was conducted in the Center for Rehabilitation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands The study was observational and conducted on 30 diabetic patients (aged 37 - 82 years) with a neuropathy. Posture stability (body sway) was assessed in a shoe without insole, on a flat insole with a low Shore A value (15 degrees) and on a flat insole with a higher Shore A value (30 degrees). These assessments were done under four different conditions: (1) eyes open, no dual-task, (2) eyes closed, no dual-task, (3) eyes open, dual-task (mental arithmetic) and (4) eyes closed, dual-task. Additionally 10 healthy controls (aged 27 - 51 years) were assessed similarly. A significantly higher root-mean-square (rms) value of the anterior-posterior velocity, V(y), was found in patients compared with controls (3.4 cm/s vs. 1.2 cm/s, p insoles or dual tasks for the total group. In diabetic patients no significant effect was found of insoles on posture stability. The effect of closed eyes on posture stability was significantly larger for diabetic patients compared to controls. It was found that prescribing insoles with a low Shore A value (15 degrees), compared to insoles with a higher Shore A value (30 degrees) has no significant negative effect on posture stability in patients with a diabetic neuropathy.

  7. [Autonomic neuropathies].

    Science.gov (United States)

    Siepmann, T; Penzlin, A I; Illigens, B M W

    2013-07-01

    Autonomic neuropathies are a heterogeneous group of diseases that involve damage of small peripheral autonomic Aδ- and C-fibers. Causes of autonomic nerve fiber damage are disorders such as diabetes mellitus and HIV-infection. Predominant symptoms of autonomic neuropathy are orthostatic hypotension, gastro-intestinal problems, urogenital dysfunction, and cardiac arrhythmia, which can severely impair the quality of life in affected patients. Furthermore, autonomic neuropathies can be induced by autoimmune diseases such as acute inflammatory demyelinating polyneuropathy, hereditary disorders such as the lysosomal storage disorder Fabry disease and hereditary sensory and autonomic neuropathies, as well as certain toxins and drugs.

  8. Autonomic Neuropathy

    Science.gov (United States)

    ... harm. Alpha-lipoic acid Preliminary research suggests this antioxidant may be helpful in slowing or even reversing ... electrical waves transmitted through electrodes placed on the skin, may help ease pain associated with diabetic neuropathy. ...

  9. Subclinical neuropathy in diabetic patients: a risk factor for bilateral lower limb neurological deficit following spinal anesthesia?

    Science.gov (United States)

    Angadi, Darshan S; Garde, Ajit

    2012-02-01

    Total knee arthroplasty performed under spinal or general anesthesia is a common successful orthopedic procedure. Nonetheless, in patients with diabetes mellitus this procedure can present unique challenges to orthopedic surgeon and anesthesiologist alike. We describe a case of an elderly male diabetic patient who developed bilaterally symmetrical lower limb neurological deficit following an uneventful total knee arthroplasty performed under spinal anesthesia. Postoperative nerve conduction study with electromyography confirmed symmetrical extensive denervation of lower limb muscles, including low-voltage fibrillation potentials and positive sharp waves. These findings were consistent with a preexisting neuropathy, thereby suggesting a subclinical neuropathy as a potential risk factor for this neurological complication. Our case highlights the fact that patients with longstanding comorbidities, namely peripheral vascular disease and diabetes mellitus, may be at an increased risk of neurological injury following regional anesthesia. Hence, we believe that preoperative evaluation of diabetic patients should include neurophysiological studies to identify subclinical neuropathy and minimize the risk of neurological injury.

  10. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy

    NARCIS (Netherlands)

    Meerwaldt, R; Links, TP; Graaff, R; Hoogenberg, K; Lefrandt, JD; Baynes, JW; Gans, ROB; Smit, AJ

    Aims/hypothesis: The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence

  11. Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy: a meta-analysis of 16 randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Bing Pang

    2016-01-01

    Conclusion: HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities. Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy. However, the methodological quality of the randomized controlled trials was generally low. Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

  12. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy

    NARCIS (Netherlands)

    Meerwaldt, R; Links, TP; Graaff, R; Hoogenberg, K; Lefrandt, JD; Baynes, JW; Gans, ROB; Smit, AJ

    2005-01-01

    Aims/hypothesis: The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence Rea

  13. HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy.

    Science.gov (United States)

    Walwyn, W M; Matsuka, Y; Arai, D; Bloom, D C; Lam, H; Tran, C; Spigelman, I; Maidment, N T

    2006-03-01

    A previous phase III clinical trial failed to show significant therapeutic benefit of repeated subcutaneous nerve growth factor (NGF) administration in the treatment of diabetic neuropathy. Animal studies have since shown that site-specific viral-mediated expression of NGF in the lumbar dorsal root ganglia prevents peripheral nerve dysfunction associated with chemically induced neuropathy. Using a Herpes simplex virus expression vector, we have investigated the effect of localized NGF expression in a genetic mouse model of progressive diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery of NGF initially delayed the appearance of hypoalgesia, assessed by the Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months over the approximately 10 months normal life-span of these animals. Once the disease progressed into its more severe stages, NGF, although still capable of altering the electrophysiological profile of the sensory A- and C-fibers and influencing the expression of p75 and substance P in the dorsal root ganglia, could no longer maintain normal nociception. These data suggest that maximal therapeutic benefit in future NGF-based gene therapy trials will be gained from early applications of such viral-mediated neurotrophin delivery.

  14. Postural Control and Gait Performance in the Diabetic Peripheral Neuropathy: A Systematic Review.

    Science.gov (United States)

    Mustapa, Amirah; Justine, Maria; Mohd Mustafah, Nadia; Jamil, Nursuriati; Manaf, Haidzir

    2016-01-01

    Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN). Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD), EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were "postural control," "balance," "gait performance," "diabetes mellitus," and "diabetic peripheral neuropathy." Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.

  15. Postural Control and Gait Performance in the Diabetic Peripheral Neuropathy: A Systematic Review

    Science.gov (United States)

    Mustapa, Amirah; Mohd Mustafah, Nadia; Jamil, Nursuriati

    2016-01-01

    Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN). Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD), EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were “postural control,” “balance,” “gait performance,” “diabetes mellitus,” and “diabetic peripheral neuropathy.” Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults. PMID:27525281

  16. Postural Control and Gait Performance in the Diabetic Peripheral Neuropathy: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Amirah Mustapa

    2016-01-01

    Full Text Available Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN. Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD, EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were “postural control,” “balance,” “gait performance,” “diabetes mellitus,” and “diabetic peripheral neuropathy.” Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.

  17. Effect of low level laser therapy on neurovascular function of diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Abeer A. Yamany

    2012-01-01

    Full Text Available Diabetic neuropathy is the most common complication and greatest source of morbidity and mortality in diabetic patients. Thirty male and female patients with painful diabetic neuropathy and abnormal results from nerve conduction studies participated in this study. Their ages ranged from 45 to 60 years with a mean of 52.1 ± SD 4.7 years. Patients were randomly assigned into two equal groups of 15, an active laser group (laser group and a placebo laser group (control group. The laser group received scanning helium neon (He–Ne infrared laser with wavelength 850 nm and density of 5.7 J/cm2, applied to the lumbosacral area and the plantar surface of the foot for 15 min each site/session three times per week for four weeks (i.e. 12 sessions. Pain intensity via visual analogue scale, bilateral peroneal motor nerves, sural sensory nerves conduction velocity and amplitude and foot skin microcirculation, were measured pre- and post-treatment for both groups. Pain was significantly decreased (p ⩽ 0.05 and electrophysiological parameters and foot skin microcirculation were significantly improved (p ⩽ 0.05 in the laser group, while no significant change was obtained in the control group. Low level laser therapy within the applied parameters and technique could be an effective therapeutic modality in reducing pain and improving neurovascular function in patients with diabetic polyneuropathy.

  18. Educational strategies for diabetic people at risk for foot neuropathy: synthesis of good evidence

    Directory of Open Access Journals (Sweden)

    Luciana Catunda Gomes de Menezes

    2016-12-01

    Full Text Available The aim of the present study was to identify the best evidence concerning health education strategies used in teaching-learning for people with diabetes mellitus who are at risk for foot neuropathy. An integrative review was conducted in the databases PubMed, LILACS, CINAHL and SCOPUS in January 2015; a total of 14 papers was analyzed in detail. The results are shown in a summary table and categories are discussed, covering various health education strategies for prevention and management with patients at risk of foot neuropathy (group; individual in face-to-face visits or via telephone; and using interactive technologies, and a synthesis of the best evidence for the effectiveness of these interventions in reducing diabetic foot complications. It was concluded that all the educational strategies are effective in promoting diabetic foot self-care. However, the group strategies showed greater effectiveness, enabling significant improvements in the knowledge, attitude, and practices of care for feet and general health of diabetic patients.

  19. Prediction of protective sensory loss, neuropathy and foot ulceration in type 2 diabetes

    Science.gov (United States)

    Paisey, R B; Darby, T; George, A M; Waterson, M; Hewson, P; Paisey, C F; Thomson, M P

    2016-01-01

    Objectives To prospectively determine clinical and biochemical characteristics associated with the development of peripheral neuropathy, loss of protective sensation, and foot ulceration in persons with type 2 diabetes mellitus (DM) over 7 years. Research design and methods Graded monofilament (MF) testing, vibration perception threshold, and neuropathy symptom questionnaires were undertaken in 206 participants with type 2 DM without peripheral vascular disease or history of foot ulceration and 71 healthy participants without DM at baseline and after 7 years. 6 monthly glycosylated hemoglobin (HbA1c) levels and annual serum lipid profiles were measured during follow-up of those with DM. Incident foot ulceration was recorded at follow-up. Results Taller stature and higher quartiles of serum triglyceride and HbA1c levels were associated with neuropathy at follow-up (p=0.008). Remission of baseline neuropathy was observed in 7 participants at follow-up. 9 participants with type 2 DM developed foot ulcers by the end of the study, only 1 at low risk. Mean HbA1c levels were higher in those who developed foot ulceration (pCharcot foot. Failure to perceive 2 or more 2, 4 and 6 g MF stimuli at baseline predicted loss of protective sensation at follow-up. Conclusions Tall stature and worse metabolic control were associated with progression to neuropathy. Mean HbA1c levels were higher in those who developed foot ulcers. Graded MF testing may enrich recruitment to clinical trials and assignation of high risk for foot ulceration. PMID:27239314

  20. Relationships between Brachial-Ankle Pulse Wave Velocity and Peripheral Neuropathy in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Byung Kil Ha

    2012-12-01

    Full Text Available BackgroundBrachial-ankle pulse wave velocity (baPWV is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN in patients with type 2 diabetes.MethodsA retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS, ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.ResultsPatients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021 and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005.ConclusionIncreased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.

  1. Favorable impact of a vegan diet with exercise on hemorheology: implications for control of diabetic neuropathy.

    Science.gov (United States)

    McCarty, Mark F

    2002-06-01

    A little-noticed clinical report indicates that a low-fat, whole-food vegan diet, coupled with daily walking exercise, leads to rapid remission of neuropathic pain in the majority of type 2 diabetics expressing this complication. Concurrent marked improvements in glycemic control presumably contribute to this benefit, but are unlikely to be solely responsible. Consideration should be given to the possibility that improved blood rheology - decreased blood viscosity and increased blood filterability - plays a prominent role in mediating this effect. There is considerable evidence that neural hypoxia, secondary to impaired endoneurial microcirculatory perfusion, is a crucial etiologic factor in diabetic neuropathy; the unfavorable impact of diabetes on hemorheology would be expected to exacerbate endoneurial ischemia. Conversely, measures which improve blood fluidity would likely have a beneficial impact on diabetic neuropathy. There is indeed evidence that vegan diets, as well as exercise training, tend to decrease the viscosity of both whole blood and plasma; reductions in hematocrit and in fibrinogen may contribute to this effect. The fact that vegan diets decrease the white cell count is suggestive of an improvement in blood filterability as well; filterability improves with exercise training owing to an increase in erythrocyte deformability. Whether these measures influence the activation of leukocytes in diabetics - an important determinant of blood filterability - remains to be determined. There are various reasons for suspecting that a vegan diet can reduce risk for other major complications of diabetes - retinopathy, nephropathy, and macrovascular disease - independent of its tendency to improve glycemic control in type 2 patients. The vegan diet/exercise strategy represents a safe, 'low-tech' approach to managing diabetes that deserves far greater attention from medical researchers and practitioners.

  2. Autonomic neuropathies

    Science.gov (United States)

    Low, P. A.

    1998-01-01

    A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

  3. Screening for peripheral neuropathy and peripheral arterial disease in persons with diabetes mellitus in a Nigerian University Teaching Hospital.

    Science.gov (United States)

    Ogbera, Anthonia O; Adeleye, Olufunmilayo; Solagberu, Babatunde; Azenabor, Alfred

    2015-10-04

    Identifying the risk factors for diabetes mellitus related foot ulceration would save more limbs from amputation. This report focuses on the determining the burden of peripheral arterial disease and neuropathy in persons with diabetes mellitus (DM). This is a descriptive study carried out in the Diabetic Clinic of the Lagos State University Teaching Hospital in patients with DM who had no past/present history of foot ulceration. Biothesiometry was employed and ankle brachial pressure indices were measured to evaluate for neuropathy and peripheral arterial disease (PAD) respectively. A total of 225 persons living with DM who met inclusion criteria were recruited consecutively over a 3 months period. Age range was 28-87 years with the mean [61.4 (10.8)] and median (63) years respectively. Patients symptomatic for neuropathy and PAD were 37 and 40 % respectively of the study population. An older age of >60 years and poor glycaemic control were potential predictors of neuropathy. Neuropathy and PAD occurred commonly in the seventh decade of life. Given the fairly high proportions of neuropathy and PAD in our patients with DM, we recommend that they be routinely examined in persons with DM.

  4. Intralimb Coordination Patterns in Absent, Mild, and Severe Stages of Diabetic Neuropathy: Looking Beyond Kinematic Analysis of Gait Cycle.

    Directory of Open Access Journals (Sweden)

    Liu Chiao Yi

    Full Text Available Diabetes Mellitus progressively leads to impairments in stability and joint motion and might affect coordination patterns, mainly due to neuropathy. This study aims to describe changes in intralimb joint coordination in healthy individuals and patients with absent, mild and, severe stages of neuropathy.Forty-seven diabetic patients were classified into three groups of neuropathic severity by a fuzzy model: 18 without neuropathy (DIAB, 7 with mild neuropathy (MILD, and 22 with moderate to severe neuropathy (SVRE. Thirteen healthy subjects were included as controls (CTRL. Continuous relative phase (CRP was calculated at each instant of the gait cycle for each pair of lower limb joints. Analysis of Variance compared each frame of the CRP time series and its standard deviation among groups (α = 5%.For the ankle-hip CRP, the SVRE group presented increased variability at the propulsion phase and a distinct pattern at the propulsion and initial swing phases compared to the DIAB and CTRL groups. For the ankle-knee CRP, the 3 diabetic groups presented more anti-phase ratios than the CTRL group at the midstance, propulsion, and terminal swing phases, with decreased variability at the early stance phase. For the knee-hip CRP, the MILD group showed more in-phase ratio at the early stance and terminal swing phases and lower variability compared to all other groups. All diabetic groups were more in-phase at early the midstance phase (with lower variability than the control group.The low variability and coordination differences of the MILD group showed that gait coordination might be altered not only when frank evidence of neuropathy is present, but also when neuropathy is still incipient. The ankle-knee CRP at the initial swing phase showed distinct patterns for groups from all degrees of neuropathic severity and CTRLs. The ankle-hip CRP pattern distinguished the SVRE patients from other diabetic groups, particularly in the transitional phase from stance to

  5. Diabetic peripheral neuropathy may not be as its name suggests: evidence from magnetic resonance imaging.

    Science.gov (United States)

    Tesfaye, Solomon; Selvarajah, Dinesh; Gandhi, Rajiv; Greig, Marni; Shillo, Pallai; Fang, Fang; Wilkinson, Iain D

    2016-02-01

    Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include distressing painful neuropathic symptoms and insensitivity to trauma that result in foot ulcerations and amputations. Several recent studies have implicated poor glycemic control, duration of diabetes, hyperlipidemia (particularly hypertryglyceridaemia), elevated albumin excretion rates, and obesity as risk factors for the development of DPN. However, similar data are not available for painful DPN. Moreover, although there is now strong evidence for the importance of peripheral nerve microvascular disease in the pathogenesis of DPN, peripheral structural biomarkers of painful DPN are lacking. However, there is now emerging evidence for the involvement of the central nervous system in both painful and painless DPN afforded by magnetic resonance imaging. This review will focus on this emerging evidence for central changes in DPN, hitherto considered a peripheral nerve disease only.

  6. Calcium signalling in sensory neurones and peripheral glia in the context of diabetic neuropathies.

    Science.gov (United States)

    Verkhratsky, Alexei; Fernyhough, Paul

    2014-11-01

    Peripheral sensory nervous system is comprised of neurones with their axons and neuroglia that includes satellite glial cells in sensory ganglia, myelinating, non-myelinating and perisynaptic Schwann cells. Pathogenesis of peripheral diabetic polyneuropathies is associated with aberrant function of both neurones and glia. Deregulated Ca(2+) homoeostasis and aberrant Ca(2+) signalling in neuronal and glial elements contributes to many forms of neuropathology and is fundamental to neurodegenerative diseases. In diabetes both neurones and glia experience metabolic stress and mitochondrial dysfunction which lead to deregulation of Ca(2+) homeostasis and Ca(2+) signalling, which in their turn lead to pathological cellular reactions contributing to development of diabetic neuropathies. Molecular cascades responsible for Ca(2+) homeostasis and signalling, therefore, can be regarded as potential therapeutic targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The Induction of Heme Oxygenase 1 Decreases Painful Diabetic Neuropathy and Enhances the Antinociceptive Effects of Morphine in Diabetic Mice.

    Directory of Open Access Journals (Sweden)

    Sílvia Castany

    Full Text Available Painful diabetic neuropathy is a common complication of diabetes mellitus which is poorly controlled by conventional analgesics. This study investigates if treatment with an heme oxygenase 1 (HO-1 inducer, cobalt protoporphyrin IX (CoPP, could modulate the allodynia and hyperalgesia induced by diabetes and enhanced the antinociceptive effects of morphine. In a diabetic mice model induced by the injection of streptozotocin (STZ, we evaluated the antiallodynic and antihyperalgesic effects produced by the intraperitoneal administration of 5 and 10 mg/kg of CoPP at several days after its administration. The antinociceptive actions produced by the systemic administration of morphine alone or combined with CoPP were also evaluated. In addition, the effects of CoPP treatment on the expression of HO-1, the microglial activation marker (CD11b/c, the inducible nitric oxide synthase (NOS2 and μ-opioid receptors (MOR, were also assessed. Our results showed that the administration of 10 mg/kg of CoPP during 5 consecutive days completely blocked the mechanical and thermal hypersensitivity induced by diabetes. These effects are accompanied by the increased spinal cord, dorsal root ganglia and sciatic nerve protein levels of HO-1. In addition, the STZ-induced activation of microglia and overexpression of NOS2 in the spinal cord were inhibited by CoPP treatment. Furthermore, the antinociceptive effects of morphine were enhanced by CoPP treatment and reversed by the administration of an HO-1 inhibitor, tin protoporphyrin IX (SnPP. The spinal cord expression of MOR was also increased by CoPP treatment in diabetic mice. In conclusion, our data provide the first evidence that the induction of HO-1 attenuated STZ-induced painful diabetic neuropathy and enhanced the antinociceptive effects of morphine via inhibition of microglia activation and NOS2 overexpression as well as by increasing the spinal cord levels of MOR. This study proposes the administration of Co

  8. Quantifying dynamic changes in plantar pressure gradient in diabetics with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Chi-Wen Lung

    2016-07-01

    Full Text Available Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP and peak pressure gradient (PPG during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking, and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG and PGA were calculated for four foot regions - 1st toe (T1, 1st metatarsal head (M1, 2nd metatarsal head (M2, and heel (HL. Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared to non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P=0.02 and PPG was 214% (P<0.001 larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P=0.04, suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers.

  9. Quantifying Dynamic Changes in Plantar Pressure Gradient in Diabetics with Peripheral Neuropathy

    Science.gov (United States)

    Lung, Chi-Wen; Hsiao-Wecksler, Elizabeth T.; Burns, Stephanie; Lin, Fang; Jan, Yih-Kuen

    2016-01-01

    Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP) and peak pressure gradient (PPG) during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA) has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG, and PGA were calculated for four foot regions – first toe (T1), first metatarsal head (M1), second metatarsal head (M2), and heel (HL). Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared with non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P = 0.02) and PPG was 214% (P < 0.001) larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P = 0.04), suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers. PMID:27486576

  10. An evaluation of structural changes in diabetic neuropathy. Clinical study with magnetic resonance imaging (MRI)

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kikuko; Suzuki, Eiji; Shibata, Toshiroh [Gifu Univ. (Japan). School of Medicine] [and others

    1996-01-01

    To investigate changes in tissue hydration and structural changes in diabetic patients using an MRI scanner (SIGNA 1.5-Tesla) with an extremity coil, spin-lattice relaxation time (T{sub 1} value), cross-sectional area, and coefficient of variation (CV value) of signal intensities of the sural nerve, respectively, were determined as indexes of nerve edema, nerve swelling or shrinkage and structural change, and were calculated in normal subjects (normal group, n=7) and diabetic patients (diabetic group, n=33). T{sub 1} value of the sural nerve, but not muscle or adipose tissue, was significantly prolonged in diabetic group (1000{+-}273 vs 702{+-}324 msec, P<0.01), indicating the presence of nerve edema in the diabetic group. There were no differences in cross-sectional area. CV values were significantly higher in the diabetic group (P<0.05). T{sub 1} values were positively correlated with glycemic control (fasting plasma glucose: r=40, HbA{sub 1}c: r=0.35) (P<0.05) and negatively correlated with motor nerve conduction velocity (r=-0.42, P<0.01). These findings indicate that MRI is of value in the objective evaluation of structural changes in diabetic neuropathy. (author).

  11. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  12. Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy.

    Science.gov (United States)

    Urban, Michael J; Pan, Pan; Farmer, Kevin L; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2012-05-01

    Quantification of intra-epidermal nerve fibers (iENFs) is an important approach to stage diabetic peripheral neuropathy (DPN) and is a promising clinical endpoint for identifying beneficial therapeutics. Mechanistically, diabetes decreases neuronal mitochondrial function and enhancing mitochondrial respiratory capacity may aid neuronal recovery from glucotoxic insults. We have proposed that modulating the activity and expression of heat shock proteins (Hsp) may be of benefit in treating DPN. KU-32 is a C-terminal Hsp90 inhibitor that improved thermal hypoalgesia in diabetic C57Bl/6 mice but it was not determined if this was associated with an increase in iENF density and mitochondrial function. After 16 weeks of diabetes, Swiss Webster mice showed decreased electrophysiological and psychosensory responses and a >30% loss of iENFs. Treatment of the mice with ten weekly doses of 20mg/kg KU-32 significantly reversed pre-existing deficits in nerve conduction velocity and responses to mechanical and thermal stimuli. KU-32 therapy significantly reversed the pre-existing loss of iENFs despite the identification of a sub-group of drug-treated diabetic mice that showed improved thermal sensitivity but no increase in iENF density. To determine if the improved clinical indices correlated with enhanced mitochondrial activity, sensory neurons were isolated and mitochondrial bioenergetics assessed ex vivo using extracellular flux technology. Diabetes decreased maximal respiratory capacity in sensory neurons and this deficit was improved following KU-32 treatment. In conclusion, KU-32 improved physiological and morphologic markers of degenerative neuropathy and drug efficacy may be related to enhanced mitochondrial bioenergetics in sensory neurons.

  13. Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: a single blind, parallel group randomized controlled trial.

    Science.gov (United States)

    Dixit, Snehil; Maiya, Arun G; Shastry, B A

    2014-01-01

    To evaluate the effect of moderate intensity aerobic exercise (40%-60% of Heart Rate Reserve (HRR)) on diabetic peripheral neuropathy. A parallel-group, randomized controlled trial was carried out in a tertiary health care setting, India. The study comprised of experimental (moderate intensity aerobic exercise and standard care) and control groups (standard care). Population with type 2 diabetes with clinical neuropathy, defined as a minimum score of seven on the Michigan Diabetic Neuropathy Score (MDNS), was randomly assigned to experimental and control groups by computer generated random number tables. RANOVA was used for data analysis (pexercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. [Response of pancreatic polypeptide to a protein rich meal in insulin non dependent diabetes melitus and autonomic neuropathy].

    Science.gov (United States)

    Kostić, N; Zamaklar, M; Novaković, R; Stajić, S

    1994-01-01

    Parasympathetic function and plasma hPP response to a protein rich meal were evaluated in 105 insulin non-dependent diabetic patients: 20 with autonomic neuropathy (group A), diagnosed by Clonidin test; 35 patients with neurophysiological evidence of polyneuropath (group B); 30 patients with autonomic neuropathy and polineuropathy (group C), and 20 patients without any sign of neuropathy (group D). Plasma hPP levels were determined by RIA using an anti-hPP antiserum, kindly provided by Prof. S. R. Bloom (Hammersmith Hospital, London). Blood was taken at 0. 45 and 60 minutes after the beginning of the meal. In groups A and C, the meal induced hPP increase was significantly lower than in group D (p 0.001). All group B patients had a marked increase in the peptide, similar to that in diabetics without neuropathy. These result ssuggest that diabetic autonomic neuropathy is associated with dysfunction of hPP secretion, and that the evaluation of hPP response to test meal may be a sensitive and simple method for the assessment of paraympathetic impairment in diabetes.

  15. Mitochondrial dysfunction in diabetic neuropathy: a series of unfortunate metabolic events.

    Science.gov (United States)

    Fernyhough, Paul

    2015-11-01

    Diabetic neuropathy is a dying back neurodegenerative disease of the peripheral nervous system where mitochondrial dysfunction has been implicated as an etiological factor. Diabetes (type 1 or type 2) invokes an elevation of intracellular glucose concentration simultaneously with impaired growth factor support by insulin, and this dual alteration triggers a maladaptation in metabolism of adult sensory neurons. The energy sensing pathway comprising the AMP-activated protein kinase (AMPK)/sirtuin (SIRT)/peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) signaling axis is the target of these damaging changes in nutrient levels, e.g., induction of nutrient stress, and loss of insulin-dependent growth factor support and instigates an aberrant metabolic phenotype characterized by a suppression of mitochondrial oxidative phosphorylation and shift to anaerobic glycolysis. There is discussion of how this loss of mitochondrial function and transition to overreliance on glycolysis contributes to the diminishment of collateral sprouting and axon regeneration in diabetic neuropathy in the context of the highly energy-consuming nerve growth cone.

  16. Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?

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    M. C. Perez-Matos

    2017-01-01

    Full Text Available Diabetic polyneuropathy (DPN encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe, triglyceride-reducing (fibrates, or lipid antioxidant (thioctic acid therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.

  17. Subclinical peripheral neuropathy in type 1 diabetic adolescents and its relationship with metabolic control

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    Sajić Silvija

    2005-01-01

    Full Text Available Professional management of paediatric diabetology, according to consensus guidelines, involves the screening of micro-vascular complications at puberty. The subclinical form of peripheral neural dysfunction in diabetic teenagers is reported with a frequency of 50-88%, by different authors. The purpose of this study was to evaluate the frequency of subclinical distal neuropathy (DSMN in type 1 diabetic pediatric patients during the second decade of life, and its relationship with metabolic control. The Endocrinology Department and the Neurology-Physiology Laboratory of the Pediatric Clinic in Belgrade carried out a longitudinal follow-up study (lasting 18 months, beginning in November 2000 on a selection of patients with poor metabolic control. During routine clinical treatment, patients were evaluated using the electrophysiological diagnostic method on peripheral neural dysfunction, a subclinical form of neuropathy. Metabolic control was manifested through HbA1c levels, measured every 3 months, using ion-exchange chromatography. Finally, here is the data collected from the clinical follow-up investigation of 60 children, aged 13-19 (median 1S.S±2.2, with duration of diabetes from 2-16 years (median b.3±3.b, and on the following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/day, median 1.02 (0.6-2.1 U/kg. Detected DSMN parameters at the beginning and at the end of the study were also noted. DSMN frequency was positive, at 64% for HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of 10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52; 6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of the examinations were unfinished (+/*. ANOVA statistical analysis showed a significant statistical relationship between metabolic control (HbA1c levels and DSMN neuropathy (sig. 0.043, p<0.05. There was no significant relationship between the reversion of

  18. MDCT assessment of CAD in type-2 diabetic subjects with diabetic neuropathy: the role of Charcot neuro-arthropathy

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    Marano, Riccardo; Savino, Giancarlo; Merlino, Biagio; Pirro, Federica; Rutigliano, Claudia; Santangelo, Carolina; Minoiu, Aurelian Costin; Natale, Luigi; Bonomo, Lorenzo [Catholic University of Rome, ' ' A. Gemelli' ' University Hospital, Department of Radiological Sciences - Institute of Radiology, Rome (Italy); Pitocco, Dario [Catholic University of Rome, ' ' A. Gemelli' ' University Hospital, Department of Internal Medicine, Rome (Italy); Di Stasio, Enrico [Catholic University of Rome, ' ' A. Gemelli' ' University Hospital, Department of Clinical Biochemistry, Rome (Italy); Trani, Carlo [Catholic University of Rome, ' ' A. Gemelli' ' University Hospital, Department of Cardiovascular Medicine - Institute of Cardiology, Rome (Italy)

    2016-03-15

    To compare the CACS and CAD severity assessed by MDCT in neuropathic type-2 diabetic patients with and without Charcot-neuroarthropathy (CN). Thirty-four CN asymptomatic-patients and 36 asymptomatic-patients with diabetic-neuropathy (DN) without CN underwent MDCT to assess CACS and severity of CAD. Patients were classified as positive for significant CAD in presence of at least one stenosis >50 % on MDCT-coronary-angiography (MDCT-CA). Groups were matched for age, sex and traditional CAD risk-factors. The coronary-angiography (CA) was performed in all patients with at least a significant stenosis detected by MDCT-CA, both as reference and eventually as treatment. CN patients showed higher rates of significant CAD in comparison with DN subjects [p < 0.001], while non-significant differences were observed in CACS (p = 0.980). No significant differences were also observed in CACS distribution in all subjects for stenosis ≥/<50 % (p = 0.814), as well as in both groups (p = 0.661 and 0.559, respectively). The MDCT-CA showed an overall diagnostic-accuracy for significant CAD of 87 %. These preliminary data suggest that CN-patients have a higher prevalence of severe CAD in comparison with DN-patients, while coronary plaques do not exhibit an increased amount of calcium. MDCT may be helpful to assess the CV risk in such asymptomatic type-2-diabetic patients with autonomic-neuropathy. (orig.)

  19. Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy.

    Science.gov (United States)

    Rahman, Md Habibur; Jha, Mithilesh Kumar; Kim, Jong-Heon; Nam, Youngpyo; Lee, Maan Gee; Go, Younghoon; Harris, Robert A; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Suk, Kyoungho

    2016-03-11

    The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy.

  20. Prevalence and related risk-factors of peripheral neuropathy in children with insulin-dependent diabetes mellitus

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    Nasibeh Hasani

    2013-01-01

    Full Text Available Background: Diabetes mellitus (DM is a common metabolic disorder that can cause various complications including, peripheral neuropathy (PNP. Some possible risk-factors such as blood glucose level, hyperglycemia, duration of diabetes, and lipid profiles are assumed to be important in diabetic PNP incidence. The aim of this study is to evaluate the prevalence and possible risk-factors of PNP in children with insulin dependent DM. Materials and Methods: Among diabetic children, 146 patients (up to 18-years old were evaluated in this cross-sectional study. All patients were examined for signs and symptoms of neuropathy and nerve conduction studies were performed. Blood level of glucose and lipid profiles were also tested. The relation between variables was compared by independent t-test and logistic regression test. Results: The mean age of diabetic children was 11.9 ± 3.3 years whereas mean diabetes duration was 3.8 ± 2.9 years. PNP was detected in 40 patients (27.4% that 62.5% of them have subclinical and 37.5% have clinical neuropathy. According to logistic regression analysis, duration of diabetes was the most important factor in prevalence of PNP (5.7 ± 3.5 and 3.1 ± 2.5 years in patients with and without neuropathy respectively, P < 0.001, 95% confidence interval [1.15-1.54]. Conclusion: As most of the patients had subclinical PN, neurological assessment is recommended to detect subclinical neuropathy in asymptomatic type 1 diabetic children and it seems that the best way to prevent this complication is still rigid blood glucose control and periodic evaluations.

  1. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

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    A-ping Sun; Lu Tang; Qin Liao; Hui Zhang; Ying-shuang Zhang; Jun Zhang(UT Austin)

    2015-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only ...

  2. The prevalence, patterns and predictors of diabetic peripheral neuropathy in a developing country

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    Katulanda Prasad

    2012-05-01

    Full Text Available Abstract Prevalence of diabetes mellitus (DM has reached epidemic proportions in Sri Lanka. Presently there are studies on the community prevalence of distal peripheral neuropathy (DPN in Sri Lanka. We describe prevalence, patterns and predictors of DPN in patients with DM in Sri Lanka. Data were collected as part of a national study on DM. In new cases DPN was assessed using the Diabetic-Neuropathy-Symptom (DNS score, while in those with established diabetes both DNS and Toronto-Clinical-Scoring-System (TCSS were used. A binary logistic-regression analysis was performed with ‘presence of DPN’ as the dichomatous dependent variable and other independent co-variants. The study included 528 diabetic patients (191-new cases, with a mean age of 55.0 ± 12.4 years and 37.3% were males, while 18% were from urban areas. Prevalence of DPN according to DNS score among all patients, patients with already established diabetes and newly diagnosed patients were 48.1%, 59.1% and 28.8% respectively. Prevalence of DPN in those with established DM as assessed by TCSS was 24% and the majority had mild DPN (16.6%. The remainder of the abstract is based on subjects with established DM. The prevalence of DPN in males and female was 20.0% and 26.4% respectively. The mean age of those with and without DPN was 62.1 ± 10.8 and 55.1 ± 10.8 years respectively (p 

  3. The Influence of Peripheral Neuropathy, Gender, and Obesity on the Postural Stability of Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Herrera-Rangel, Aline; Aranda-Moreno, Catalina; Mantilla-Ochoa, Teresa; Zainos-Saucedo, Lylia; Jáuregui-Renaud, Kathrine

    2014-01-01

    Aim. To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. Methods. 151 patients with no history of otology, neurology, or orthopaedic or balance disorders accepted to participate in the study. After a clinical interview and neuropathy assessment, postural stability was evaluated by static posturography (eyes open/closed on hard/soft surface) and the “Up & Go” test. Results. During static posturography, on hard surface, the length of sway was related to peripheral neuropathy, gender, age, and obesity; on soft surface, the length of sway was related to peripheral neuropathy, gender, and age, the influence of neuropathy was larger in males than in females, and closing the eyes increased further the difference between genders. The mean time to perform the “Up & Go” test was 11.6 ± 2.2 sec, with influence of peripheral neuropathy, gender, and age. Conclusion. In order to preserve the control of static upright posture during conditions with deficient sensory input, male patients with type 2 diabetes mellitus with no history of balance disorders may be more vulnerable than females, and obesity may decrease the static postural control in both males and females. PMID:25258716

  4. Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

    Science.gov (United States)

    2014-01-01

    Background Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. Method The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. Results DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC50 values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the Cmax of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination

  5. Prostaglandin E1 alleviates neuropathic pain and neural dysfunction from entrapment neuropathy associated with diabetes mellitus.

    Science.gov (United States)

    Natsume, Tadahiro; Iwatsuki, Katsuyuki; Nishizuka, Takanobu; Arai, Tetsuya; Yamamoto, Michiro; Hirata, Hitoshi

    2014-10-01

    In this report, we present the results of investigation of the effects of prostaglandin E1 (PGE1) on entrapment neuropathy using a diabetic rat. A total of 60 male Sprague-Dawley rats were used in the study. The model of tibial nerve entrapment neuropathy associated with diabetes mellitus was created by streptozotocin-induced diabetic rats reared in cages with wire grid flooring. Rats were assigned to four groups: nondiabetic (n = 15), untreated diabetic (n = 15), diabetic treated with 30 μg/kg PGE1 (n = 15), and diabetic treated with 100 μg/kg PGE1 (n = 15). Pain tests and electrophysiological tests were performed at 0, 2, and 4 weeks, and assessments of gait, histology, and mRNA expression levels were performed at 4 weeks after initiating the PGE1 administration. In the 30 and 100 μg groups, the mechanical withdrawal thresholds measured by pain tests at 4 weeks (36.2 ± 16.4 g and 31.7 ± 15.3 g, respectively) and the motor conduction velocity (24.0 ± 0.2 m/s and 24.4 ± 0.3 m/s, respectively) were significantly higher than the untreated diabetic group (all P < 0.05) and lower than the nondiabetic group (all P < 0.001). In the gait analysis, the mean intensities in the 30 and 100 μg group (128.0 ± 20.1 a.u. and 109.0 ± 27.8 a.u., respectively) were significantly higher than the untreated diabetic (P < 0.01) and were not significantly different from the nondiabetic group (P = 0.81). Fiber density (P = 0.46) and fiber diameter (P = 0.15) did not show any significant differences. PGE1 significantly decreased nerve growth factor (NGF) mRNA and increased vascular endothelial growth factor (VEGF) mRNA in the tibial nerve (both P < 0.01). In conclusion, neurological deteriorations of diabetic rats were alleviated with PGE1, which is associated with inhibition of NGF and enhancement of VEGF at the entrapment site.

  6. Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2007-01-01

    Sildenafil citrate is a specific inhibitor of phosphodiesterase (PDE) type-5 and represents a powerful therapy for male erectile and fertility dysfunctions of different etiologies. Present study demonstrates whether sildenafil administration modifies seminal parameters in diabetic neuropathic patients. In this investigation 50 insulin dependent (IDDM) and 50 non insulin dependent (NIDDM) diabetic male patients with and without an objective evidence of neuropathy and 50 age matched non diabetic male controls were selected. Every male had age between 20 to 65 years with duration of diabetes distributed over 1 to 20 years. Treatment with 100 mg of oral sildenafil citrate on seminal parameters was evaluated by semen analysis in these patients. In both IDDM and NIDDM diabetic neuropathic patients, chronic sildenafil treatment exhibited a significant decrease in total sperm output and sperm concentration (p<0.001). On the other hand, sperm motility and semen volume were found to be increased by about 40% and 48% respectively in these patients, where as sperm morphology and quality of sperm motility remained unaffected. However both types of non neuropathic diabetics showed a non significant difference in all the above mentioned parameters when compared with the untreated groups and their respective control subjects. A comparison between IDDM and NIDDM neuropathic and non neuropathic diabetic groups further indicated a non significant difference in all the parameters of semen analysis. These findings suggest a chronic neuro physiological effect of sildenafil treatment on male fertility profile exclusively in diabetic neuropathic condition with an improvement in testicular function which was probably arrested due to some kind of testicular hyperplasia resulted by testicular necrosis and promoted spermatogenesis. Sildenafil seems to be associated with an improvement in the entire smooth musculature of reproductive tract and testicular morphology which was altered due to

  7. Effects of Icariside II on Corpus Cavernosum and Major Pelvic Ganglion Neuropathy in Streptozotocin-Induced Diabetic Rats

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    Guang-Yi Bai

    2014-12-01

    Full Text Available Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg. Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily. Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro was greatly attenuated in the ICA II-treated group (p < 0.01. ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

  8. Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

    Science.gov (United States)

    Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H

    2012-09-01

    Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P heart-rate recovery parameters (range 0.80-0.83, P heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  9. Gait characteristics of people with diabetes-related peripheral neuropathy, with and without a history of ulceration.

    Science.gov (United States)

    Raspovic, Anita

    2013-09-01

    Biomechanical alterations in diabetes are believed to contribute to plantar neuropathic ulceration. This exploratory study documents clinical measures of flexibility and strength, alongside three-dimensional biomechanical gait data of the lower limb, in 10 patients with a history of neuropathic ulceration (DNU; n=10). Comparative data is presented from age and gender matched groups with; diabetes peripheral neuropathy and no ulcer history (DWN; n=10), diabetes and no peripheral neuropathy (DNN; n=10) and a non-diabetes reference group (NOND; n=10). Biomechanical data were collected at a comfortable walking speed with a Vicon motion analysis system. Clinical measures showed a non-significant trend toward decreased static range of motion at the ankle and first metatarsophalangeal joints, with worsening neuropathy status. Of the diabetes groups, knee and ankle strength was significantly lower in those with an ulcer history (p=0.01-0.03), with the exception of knee extension. In the DNU group, walking speed was on average 0.17 ms slower compared to NOND (p=0.04). The DNU group demonstrated a lower range of motion than NOND at the: hips (frontal plane, by 25%: p=0.03); hips and knees (transverse plane, 31%: p=0.01 and 32%: ppower (21%: p=0.03) and vertical ground reaction force 2nd peak (6%: pgait alterations in people with clinically severe peripheral neuropathy and related plantar foot ulcer history. Further research is needed to explore potential casual pathways.

  10. Heterogeneity in diabetic distal neuropathy and differential approach to its treatment

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    O E Khutornaya

    2013-06-01

    Full Text Available Aims. To determine the prevalence of painful diabetic neuropathy (PDN, to evaluate the composition and efficacy of pharmacotherapy and to develop a differential algorithm for symptomatic treatment of PDN.Materials and Methods. 4494 outpatient subjects participated in this study. Severity of pain syndrome was assessed with DN4 question- naire (supplemented with NTSS-9 scale and visual analogue scale (VAS. After initial examination, a pharmacological evaluation of treatment was performed.Results. Based on our data, prevalence of diabetic neuropathy was estimated at 54%, with painful form reaching 6.4%. Median age was 57.2±12.1, duration of diabetes mellitus – 16.5±10.6 years. Type 1 / type 2 ratio equaled 32.4% : 67.6%, male/female – 29.7%: 70.3%. Median HbA1c level was 8.4±1.6%. Ratio of chronic/acute forms of neuropathy was 267 : 20. Pain severity (as measured by VAS distribution was as following: 15.6% – severe, 40.6% – moderate, 12.3% – mild, and 31.3% – no pain symptoms. We did not find PDN to be associated with any parameters but sensory deficit (NTSS-9 and NDS: r=0.4; p <0.001. 21% of patients with chronic painful neuropathy (CPN demonstrated allodynia and hyperalgesia besides typical symptoms. 97.9% of patients were previ- ously treated with “pathogenetic” agents, 2.1% received anticonvulsants; overall efficiency was estimated at 22%. Patients with CPN and allodynia did not respond to treatment with alpha-lipoic acid (ALA, but pregabalin was efficient. After the examination treatment composition was adjusted as follows: treatment was ceased in 23% of patients, 11.9% received ALA, 53.6% – anticonvulsants, and11.5% – antidepressants; overall efficiency was estimated at 75%.Conclusion. Prevalence of PDN is relatively low. 15.6% of patients suffer from severe pain. Neuropathic pain intensity correlates only with sensory deficit and is not dependent on any other parameters. CPN consists of two forms with higher and lower

  11. The influence of diabetic peripheral neuropathy on local postural muscle and central sensory feedback balance control.

    Science.gov (United States)

    Toosizadeh, Nima; Mohler, Jane; Armstrong, David G; Talal, Talal K; Najafi, Bijan

    2015-01-01

    Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m2) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m2) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-controlslope = 1.23±1.06×10-2 cm2/sec, Pcontrol balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-controlslope-Log = 0.39±0.23, Pcontrol rate of sway with neuropathy severity (rPearson = 0.65-085, Pcontrols. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation mechanism using sensory feedback depends on the level of neuropathy and the history of diabetes.

  12. Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy

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    Alan Wright

    2010-12-01

    Full Text Available Alan Wright, Kyle E Luedtke, Chad VanDenBergCenter for Clinical Research, Mercer University, Atlanta, Georgia, USAAbstract: Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief Pain Inventory scores, the Clinical Global Impressions Scale, and other various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies. Symptom improvement generally began within the first few weeks, and continued for the duration of the study. In addition, the efficacy of duloxetine was found to be due to direct effects on pain symptoms rather than secondary to improvements in depression or anxiety. Adverse events including nausea, constipation, dry mouth, and insomnia, were mild and transient and occurred at relatively low rates. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of chronic pain associated with fibromyalgia or diabetic neuropathy, and has a predictable tolerability profile, with adverse events generally being mild to moderate.Keywords: duloxetine, chronic pain, neuropathic pain, fibromyalgia, efficacy, safety

  13. Use of Natural Compounds in the Management of Diabetic Peripheral Neuropathy

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    Maria Galuppo

    2014-03-01

    Full Text Available Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics—non-steroidal anti-inflammatory drugs (NSAIDS and opioids—understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management.

  14. The Roles of Streptozotocin Neurotoxicity and Neutral Endopeptidase in Murine Experimental Diabetic Neuropathy

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    Eric Davidson

    2009-01-01

    Full Text Available We demonstrated that inhibition of neutral endopeptidase (NEP, a protease that degrades vaso- and neuroactive peptides, improves vascular and neural function in diabetic animal models. In this study we explored the role of NEP in neuropathy related to either insulin-deficient diabetes or diet-induced obesity using NEP deficient (−/− mice. Initial studies showed that streptozotocin, in the absence of subsequent hyperglycemia, did not induce nerve conduction slowing or paw thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP −/− mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP −/− mice exposed to either streptozotocin-induced diabetes or a high fat diet. These studies suggest that streptozotocin does not induce neurotoxicity in mice and that NEP plays a role in regulating nerve function in insulin-deficient diabetes and diet-induced obesity.

  15. The Roles of Streptozotocin Neurotoxicity and Neutral Endopeptidase in Murine Experimental Diabetic Neuropathy

    Science.gov (United States)

    Davidson, Eric; Coppey, Lawrence; Lu, Bao; Arballo, Victor; Calcutt, Nigel A.; Gerard, Craig; Yorek, Mark

    2009-01-01

    We demonstrated that inhibition of neutral endopeptidase (NEP), a protease that degrades vaso- and neuroactive peptides, improves vascular and neural function in diabetic animal models. In this study we explored the role of NEP in neuropathy related to either insulin-deficient diabetes or diet-induced obesity using NEP deficient (−/−) mice. Initial studies showed that streptozotocin, in the absence of subsequent hyperglycemia, did not induce nerve conduction slowing or paw thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP −/− mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP −/− mice exposed to either streptozotocin-induced diabetes or a high fat diet. These studies suggest that streptozotocin does not induce neurotoxicity in mice and that NEP plays a role in regulating nerve function in insulin-deficient diabetes and diet-induced obesity. PMID:20148083

  16. Diabetic patients with and without peripheral neuropathy reveal different hip and ankle biomechanical strategies during stair descent

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    Andreja P. Picon

    Full Text Available BACKGROUND: The progression of diabetes and the challenge of daily tasks may result in changes in biomechanical strategies. Descending stairs is a common task that patients have to deal with, however it still has not been properly studied in this population. OBJECTIVES: We describe and compare the net joint moments and kinematics of the lower limbs in diabetic individuals with and without peripheral neuropathy and healthy controls during stair descent. METHOD: Forty-two adults were assessed: control group (13, diabetic group (14, and neuropathic diabetic group (15. The flexor and extensor net moment peaks and joint angles of the hip, knee, and ankle were described and compared in terms of effect size and ANOVAs (p<0.05. RESULTS: Both diabetic groups presented greater dorsiflexion [large effect size] and a smaller hip extensor moment [large effect size] in the weight acceptance phase. In the propulsion phase, diabetics with and without neuropathy showed a greater hip flexor moment [large effect size] and smaller ankle extension [large effect size]. CONCLUSION: Diabetic patients, even without neuropathy, revealed poor eccentric control in the weight acceptance phase, and in the propulsion phase, they showed a different hip strategy, where they chose to take the leg off the ground using more flexion torque at the hip instead of using a proper ankle extension function.

  17. THE ROLE OF IGF-1 GENE EXPRESSION ABNORMALITY IN PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

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    李剑波; 汪承亚; 陈家伟; 李晓璐; 冯振卿; 马洪太

    2002-01-01

    Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P <0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P <0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P <0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P <0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ~ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ~(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P <0. 001; amplitude ofevokedpotential: r = 0. 716, P <0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P < 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.

  18. Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis (Protocol

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    Griebeler Marcio L

    2012-12-01

    Full Text Available Abstract Background Neuropathic pain can reduce the quality of life and independence of 30% to 50% of patients with diabetes. The comparative effectiveness of analgesics for patients with diabetic neuropathy remains unclear. The aim of the current work, therefore, was to summarize the evidence about the analgesic effectiveness of the most common oral and topical agents used for the treatment of peripheral diabetic neuropathy. Methods We will use an umbrella approach (systematic review of systematic reviews to identify eligible randomized controlled trials (RCTs for the most common oral or topical analgesics for painful diabetic neuropathy. Two reviewers will independently determine RCT eligibility. Disagreement will be solved by consensus and arbitrated by a third reviewer. We will extract descriptive, methodological and efficacy data in duplicate. Results will be pooled and analyzed using classic random-effects meta-analyses and network meta-analyses to compute the absolute and relative efficacy of therapeutic options. We will use the I2 statistic and Cochran’s Q test to assess heterogeneity. Risk of bias and publication bias, if appropriate, will be evaluated, as well as overall strength of the evidence. Discussion This network meta-analysis aims to synthesize available direct and indirect evidence of effectiveness of analgesics in the treatment of painful diabetic neuropathy. The network approach will offer the opportunity to generate a ranking based on efficacy and along with known side effects, costs, and administration burdens will enable patients and clinicians to make choices that best reflect their preferences for treatment of painful diabetic neuropathy.

  19. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

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    A-ping Sun

    2015-01-01

    Full Text Available Charcot-Marie-Tooth disease type 1A (CMT1A is caused by duplication of the peripheral myelin protein 22 (PMP22 gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.

  20. Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction?

    DEFF Research Database (Denmark)

    Rasmussen, M H; Carstensen, H; List, S;

    1993-01-01

    The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response...... is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion......, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 15 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response...

  1. Implementing a clinical assessment protocol for sensory and skeletal function in diabetic neuropathy patients at a university hospital in Brazil

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    Isabel de Camargo Neves Sacco

    Full Text Available CONTEXT AND OBJECTIVE: Physiotherapy can contribute towards recovering or preventing physical and sensory alterations in diabetic neuropathy patients. Our objective was to create and apply a protocol for functional assessment of diabetic neuropathy patients' lower limbs, to guide future physiotherapy. DESIGN AND SETTING: Clinical study at the University Hospital and teaching/research center of Universidade de São Paulo. METHODS: An intentional sample of diabetic neuropathy patients was utilized. The protocol was divided into: (1 preliminary investigation with identification of relevant clinical diabetes and neuropathy characteristics; (2 thermal, tactile and proprioceptive sensitivity tests on the feet; (3 evaluations of muscle function, range of motion, lower limb function, foot anthropometry. RESULTS: The patients' mean age was 57 years, and they had had the diagnosis for 13 years on average. Distal numbness and tingling/prickling were present in 62% and 67%, respectively. There were tactile sensitivity alterations above the heel in 50%, with thermal sensitivity in 40% to 60%. The worst muscle function test responses were at the triceps surae and foot intrinsic muscles. Longitudinal plantar arches were lowered in 50%. Decreased thermal and tactile sensitivity of the heels was found. There was a general reduction in range of motion. CONCLUSIONS: The results provided detailed characterization of the patients. This protocol may be easily applied in healthcare services, since it requires little equipment, at low cost, and it is well understood by patients.

  2. Corneal confocal microscopy best identifies the development and progression of neuropathy in patients with type 1 diabetes.

    Science.gov (United States)

    Edwards, Katie; Pritchard, Nicola; Dehghani, Cirous; Vagenas, Dimitrios; Russell, Anthony; Malik, Rayaz A; Efron, Nathan

    2017-08-01

    A sub-set of 38 individuals with type 1 diabetes that fulfilled a strict criterion of "normal" classification for all 7 measures of neuropathy at baseline, were identified and followed. Corneal nerve morphology, as captured with corneal confocal microscopy demonstrated the greatest, and most sustained degeneration over a 4 year period. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Activity-Dependent Excitability Changes Suggest Na[superscript +]/K[superscript +] Pump Dysfunction in Diabetic Neuropathy

    Science.gov (United States)

    Krishnan, Arun V.; Lin, Cindy S.-Y.; Kiernan, Matthew C.

    2008-01-01

    The present study was undertaken to evaluate the role of Na[superscript +]/K[superscript +] pump dysfunction in the development of diabetic neuropathy (DN). Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, were undertaken in 15 patients with established DN and in 10 patients with…

  4. 4-Hydroxy-2-nonenal induces mitochondrial dysfunction and aberrant axonal outgrowth in adult sensory neurons that mimics features of diabetic neuropathy.

    Science.gov (United States)

    Akude, Eli; Zherebitskaya, Elena; Roy Chowdhury, Subir K; Girling, Kimberly; Fernyhough, Paul

    2010-01-01

    Modification of proteins by 4-hydroxy-2-nonenal (4-HNE) has been proposed to cause neurotoxicity in a number of neurodegenerative diseases, including distal axonopathy in diabetic sensory neuropathy. We tested the hypothesis that exposure of cultured adult rat sensory neurons to 4-HNE would result in the formation of amino acid adducts on mitochondrial proteins and that this process would be associated with impaired mitochondrial function and axonal regeneration. In addition, we compared 4-HNE-induced axon pathology with that exhibited by neurons isolated from diabetic rats. Cultured adult rat dorsal root ganglion (DRG) sensory neurons were incubated with varying concentrations of 4-HNE. Cell survival, axonal morphology, and level of axon outgrowth were assessed. In addition, video microscopy of live cells, western blot, and immunofluorescent staining were utilized to detect protein adduct formation by 4-HNE and to localize actively respiring mitochondria. 4-HNE induced formation of protein adducts on cytoskeletal and mitochondrial proteins, and impaired axon regeneration by approximately 50% at 3 microM while having no effect on neuronal survival. 4-HNE initiated formation of aberrant axonal structures and caused the accumulation of mitochondria in these dystrophic structures. Neurons treated with 4-HNE exhibited a distal loss of active mitochondria. Finally, the distal axonopathy and the associated aberrant axonal structures generated by 4-HNE treatment mimicked axon pathology observed in DRG sensory neurons isolated from diabetic rats and replicated aspects of neurodegeneration observed in human diabetic sensory neuropathy.

  5. Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer’s disease

    Science.gov (United States)

    Jolivalt, Corinne G.; Calcutt, Nigel A.; Masliah, Eliezer

    2011-01-01

    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 PNS. In this study, we compared indices of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and 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 GSK3β were 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. PMID:22178988

  6. Evaluation of diabetic autonomic neuropathy by [sup 123]I-metaiodobenzyl-guanidine (MIBG) cardiac imaging. Initial report

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    Osonoi, Takeshi; Fukumoto, Yoshihiro; Saitou, Miyoko; Kuroda, Yasuhisa; Uchimi, Nobuo; Ishioka, Kuniharu (Mitokyoudou General Hospital, Ibaraki (Japan)); Onuma, Tomio; Suga, Shigeki; Takebe, Kazuo

    1994-11-01

    Single-photon emission computed tomography was performed in 52 diabetics and 10 healthy volunteers using MIBG. The diabetics had no particular findings of electrocardiography, echocardiography, or exercise thallium imaging and no cardiovascular episodes. The healthy volunteers had no abnormal findings on exercise thallium imaging or glucose tolerance test. The average relative regional uptake (RRU) was decreased in the inferoposterior wall compared with the anterior or lateral wall in both the diabetics and volunteers. According to the RRU and visual images, we divided the diabetics into the following four groups: 14 who were normal (group N), 30 with segmental defects (group S), 4 with diffuse defects (group D) and 4 without accumulation (group DH). Diabetic complications (retinopathy, nephropathy, and neuropathy) and hypertension were more frequent in group S than group N. However, there were no significant differences in the physiological evidence of autonomic neuropathy (C.V. of the R-R interval on the ECG and blood pressure response to standing or deep breathing) between groups S and N. Vibration sense was significantly more impaired in group S than in group N. These results suggest that cardiac imaging with MIBG might be a useful examination for the early diagnosis of diabetic autonomic neuropathy. (author).

  7. Using dynamic pupillometry as a simple screening tool to detect autonomic neuropathy in patients with diabetes: a pilot study

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    Schneider Fábio K

    2010-06-01

    Full Text Available Abstract Background Autonomic neuropathy is a common and serious complication of diabetes. Early detection is essential to enable appropriate interventional therapy and management. Dynamic pupillometry has been proposed as a simpler and more sensitive tool to detect subclinical autonomic dysfunction. The aim of this study was to investigate pupil responsiveness in diabetic subjects with and without cardiovascular autonomic neuropathy (CAN using dynamic pupillometry in two sets of experiments. Methods During the first experiment, one flash was administered and the pupil response was recorded for 3 s. In the second experiment, 25 flashes at 1-s interval were administered and the pupil response was recorded for 30 s. Several time and pupil-iris radius-related parameters were computed from the acquired data. A total of 24 diabetic subjects (16 without and 8 with CAN and 16 healthy volunteers took part in the study. Results Our results show that diabetic subjects with and without CAN have sympathetic and parasympathetic dysfunction, evidenced by diminished amplitude reflexes and significant smaller pupil radius. It suggests that pupillary autonomic dysfunction occurs before a more generalized involvement of the autonomic nervous system, and this could be used to detect early autonomic dysfunction. Conclusions Dynamic pupillometry provides a simple, inexpensive, and noninvasive tool to screen high-risk diabetic patients for diabetic autonomic neuropathy.

  8. The Eurodiab study: what has this taught us about diabetic peripheral neuropathy?

    Science.gov (United States)

    Tesfaye, Solomon; Selvarajah, Dinesh

    2009-12-01

    Apart from tight blood glucose control, no other treatments have been shown to retard the progression of diabetic peripheral neuropathy (DPN). Therefore, identifying potential risk factors for DPN is important, particularly if they are modifiable. The Eurodiab baseline DPN study found a prevalence of 28% for DPN, with glycemic control and duration of diabetes being major determinants. It was also observed that a substantial proportion of those with good glucose control (hemoglobin A(1c) < 7%) were found to have DPN, which raised the possibility that other risk factors may be involved. Having excluded those with DPN at baseline, researchers followed 1172 type 1 diabetic subjects for 7.3 years (SD, 0.6) looking for risk factors for the development of DPN. DPN developed in 23.5% over the follow-up period; and apart from glycemic control and duration of diabetes, known to be important risk factors for DPN, traditional markers of macrovascular disease (eg, hypertension, smoking, obesity, and triglycerides) were found to be independent risk factors. The study was published in the New England Journal of Medicine and suggested that a need exists for clinical trials to confirm if modifying cardiovascular risk factors is an effective treatment for DPN.

  9. Conventional deep pressure algometry is not suitable for clinical assessment of nociception in painless diabetic neuropathy

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    Ernst A. Chantelau

    2016-09-01

    Full Text Available Background: In diabetic persons with painless neuropathic foot ulceration, foot skin was found to be insensate to noxious pinprick stimulation (stimulation area less than 0.05 mm2, while compression of deep subcutaneous foot tissues by Algometer II® (stimulation area 1 cm2 could evoke a deep dull aching. To elucidate this discrepancy, the Algometer II stimulation technique was critically reviewed by varying probe sizes and anatomical sites in the same study population 3 years later. Methods: Ten control subjects without neuropathy and 11 persons with painless diabetic neuropathy (PLDN, seven of whom with diabetic foot syndrome, i.e., past painless foot ulcer, or inactive Charcot arthropathy were re-examined using Algometer II. Deep pressure pain perception threshold (DPPPT was measured in random sequence with stimulation areas of 0.5 cm2, 1 cm2, and 2 cm2 (separated by 5 min intervals, at the plantar forefoot, the instep, and the hindfoot of both legs. Results: In the control and PLDN groups, median DPPPTs differed significantly between stimulation areas (highest with 0.5 cm2, intermediate with 1 cm2, lowest with 2 cm2; p<0.001, and varied moderately by anatomical site. Between-group differences were relatively small. Results of the 1 cm2 assessments repeated 3 years apart were similar. Conclusions: Algometer II readings represent spatial summation of low-threshold pressure-receptor rather than of high-threshold nociceptor stimulation and are, thus, unhelpful for assessing PLDN. Reproducibility of the measurements is good.

  10. Cytotoxic T Lymphocyte Antigen-4 Gene Variants in Type 2 Diabetic Patients with or without Neuropathy

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    Javad Kiani

    2016-06-01

    Full Text Available Many studies have shown that cytotoxic T lymphocyte antigen-4 (CTLA-4 gene variants are associated with several autoimmune diseases particularly type 1 diabetes. Due to the lack of consistent data for this association with type 2 diabetes (T2D, this study explored the possible influence of CTLA-4 gene polymorphisms at -1722 (T/C, -318 (C/T, and +49 (G/A positions for susceptibility to T2D in relation with neuropathy. One hundred and eleven unrelated patients with T2D [49 patients with diabetic peripheral neuropathy (DPN and 62 patients without PDN] and 100 healthy ethnic- and gender-matched controls were included in this study. The dimorphisms at -1722 (C/T, -318 (C/T and +49 (A/G for CTLA-4 gene were determined using ARMS-PCR. The CTLA-4 (+49 G/G and (+49 A/A genotypes were found to be positively and negatively associated with T2D, respectively (p=0.03. The -318 C/T and T/T genotypes were more frequent in patients than controls and -318 C/C genotype was shown to be protective for T2D (p=0.003. ACT and GTT Haplotypes were less and more frequent in controls and patients, respectively (p=3.86×10-7 and p=2.29×10-5. Genotypes distribution among T2D patients with and without DPN compared to healthy controls showed significantly lower frequencies for -318 C/C and +49 A/A genotypes and significantly higher frequencies for -318 C/T and T/T genotypes as well. Our findings indicate that CTLA-4 (+49 A/G and (-318 C/T genotypes could be considered as genetic risk factors associated with susceptibility or protection for T2D.

  11. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy.

    Science.gov (United States)

    Tesfaye, Solomon; Selvarajah, Dinesh

    2012-02-01

    Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include painful neuropathic symptoms and insensitivity, which increases the risk for burns, injuries and foot ulceration. Several recent studies have implicated poor glycaemic control, duration of diabetes, hyperlipidaemia (particularly hypertryglyceridaemia), elevated albumin excretion rates and obesity as risk factors for the development of DPN. Although there is now strong evidence for the importance of nerve microvascular disease in the pathogenesis of DPN, the risk factors for painful DPN are not known. However, emerging evidence regarding the central correlates of painful DPN is now afforded by brain imaging. The diagnosis of DPN begins with a careful history of sensory and motor symptoms. The quality and severity of neuropathic pain if present should be assessed using a suitable scale. Clinical examination should include inspection of the feet and evaluation of reflexes and sensory responses to vibration, light touch, pinprick and the 10-g monofilament. Glycaemic control and addressing cardiovascular risk is now considered important in the overall management of the neuropathic patient. Pharmacological treatment of painful DPN includes tricyclic compounds, serotonin-norepinephrine reuptake inhibitors (e.g. duloxetine), anticonvulsants (e.g. pregabalin), opiates, membrane stabilizers, the antioxidant alpha lipoic acid and others. Over the past 7 years, new agents with perhaps less side effect profiles have immerged. Management of patients with painful neuropathy must be tailored to individual requirements and will depend on the presence of other co-morbidities. There is limited literature with regard to combination treatment.

  12. Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

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    Shuyun Zhang

    2017-01-01

    Full Text Available Diabetes-triggered apoptosis of Schwann cells (SC contributes to the degradation of diabetic peripheral neuropathy (DNP. In recent years, mesenchymal stem cells (MSC were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

  13. Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

    Science.gov (United States)

    Zhang, Shuyun

    2017-01-01

    Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

  14. The influence of diabetic peripheral neuropathy on local postural muscle and central sensory feedback balance control.

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    Nima Toosizadeh

    Full Text Available Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN. Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control and central-control (postural control using sensory cueing. DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m2 and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m2 with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-controlslope = 1.23±1.06×10-2 cm2/sec, P<0.01, which suggests a compromised local-control balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-controlslope-Log = 0.39±0.23, P<0.02, which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (rPearson = 0.65-085, P<0.05 and the history of diabetes (rPearson = 0.58-071, P<0.05. Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation

  15. Plantar thermography is useful in the early diagnosis of diabetic neuropathy

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    Luciane Fachin Balbinot

    2012-12-01

    Full Text Available OBJECTIVES: This study evaluated plantar thermography sensitivity and specificity in diagnosing diabetic polyneuropathy using cardiac tests (heart rate variability as a reference standard because autonomic small fibers are affected first by this disease. METHODS: Seventy-nine individuals between the ages of 19 and 79 years old (28 males were evaluated and divided into three groups: control (n = 37, pre-diabetics (n = 13 and type 2 diabetics (n = 29. The plantar images were recorded at baseline and then minutes after a provocative maneuver (Cold Stress Test using an infrared camera that is appropriate for clinical use. Two thermographic variables were studied: the thermal recovery index and the interdigital anisothermal technique. Heart rate variability was measured in a seven-test battery that included three spectral indexes (in the frequency domain and four Ewing tests (the Valsalva maneuver, the orthostatic test, a deep breathing test, and the orthostatic hypotension test. Other classically recommended tests were applied, including electromyography (EMG, Michigan inventory, and a clinical interview that included a neurological physical examination. RESULTS: Among the diabetic patients, the interdigital anisothermal technique alone performed better than the thermal recovery index alone, with a better sensitivity (81.3% and specificity (46.2%. For the pre-diabetic patients, the three tests performed equally well. None of the control subjects displayed abnormal interdigital anisothermal readouts or thermal recovery indices, which precluded the sensitivity estimation in this sample of subjects. However, the specificity (70.6% was higher in this group. CONCLUSION: In this study, plantar thermography, which predominately considers the small and autonomic fibers that are commonly associated with a sub-clinical condition, proved useful in diagnosing diabetic neuropathy early. The interdigital anisothermal test, when used alone, performed best.

  16. Plantar thermography is useful in the early diagnosis of diabetic neuropathy

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    Balbinot, Luciane Fachin; Canani, Luis Henrique; Robinson, Caroline Cabral; Achaval, Matilde; Zaro, Milton Antônio

    2012-01-01

    OBJECTIVES: This study evaluated plantar thermography sensitivity and specificity in diagnosing diabetic polyneuropathy using cardiac tests (heart rate variability) as a reference standard because autonomic small fibers are affected first by this disease. METHODS: Seventy-nine individuals between the ages of 19 and 79 years old (28 males) were evaluated and divided into three groups: control (n = 37), pre-diabetics (n = 13) and type 2 diabetics (n = 29). The plantar images were recorded at baseline and then minutes after a provocative maneuver (Cold Stress Test) using an infrared camera that is appropriate for clinical use. Two thermographic variables were studied: the thermal recovery index and the interdigital anisothermal technique. Heart rate variability was measured in a seven-test battery that included three spectral indexes (in the frequency domain) and four Ewing tests (the Valsalva maneuver, the orthostatic test, a deep breathing test, and the orthostatic hypotension test). Other classically recommended tests were applied, including electromyography (EMG), Michigan inventory, and a clinical interview that included a neurological physical examination. RESULTS: Among the diabetic patients, the interdigital anisothermal technique alone performed better than the thermal recovery index alone, with a better sensitivity (81.3%) and specificity (46.2%). For the pre-diabetic patients, the three tests performed equally well. None of the control subjects displayed abnormal interdigital anisothermal readouts or thermal recovery indices, which precluded the sensitivity estimation in this sample of subjects. However, the specificity (70.6%) was higher in this group. CONCLUSION: In this study, plantar thermography, which predominately considers the small and autonomic fibers that are commonly associated with a sub-clinical condition, proved useful in diagnosing diabetic neuropathy early. The interdigital anisothermal test, when used alone, performed best

  17. 2型糖尿病外周感觉神经病变和心自主神经病变关系的研究%Relationship between peripheral neuropathy and cardiovascular autonomic neuropathy in type 2 diabetes

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    牛奔; 苏恒; 李超; 张云; 薛元明

    2013-01-01

    目的 探讨T2DM外周感觉神经病变和心自主神经病变之间的关系. 方法 选取T2DM患者148例,采集临床资料,测定FPG、HbA1c及LDL-C等生化指标;进行定量感觉神经检查(以色列TSA-Ⅱ定量感觉神经测定仪),结合临床症状评价糖尿病外周感觉神经病变;进行心血管反射试验检查,结合临床症状评价糖尿病心自主神经病变. 结果 外周感觉神经病变的患病率为28%,心自主神经病变的患病率为10%;无外周感觉神经病变的患者中心自主神经病变的患病率为6%,存在外周感觉神经病变的患者中心自主神经病变的患病率为21%;与对照组相比,外周感觉神经病变组和心自主神经病变组的病程较长,FPG、HbA1 c及LDL-C水平较高,差异有统计学意义(P<0.05). 结论 糖尿病心自主神经病变可发生于无外周感觉神经病变的患者;病程、FPG、HbA1c及LDL-C可能为糖尿病外周感觉神经病变和心自主神经病变的危险因素.%Objective To investigate the relationship between diabetic cardiovascular autonomic neuropathy and peripheral neuropathy in type 2 diabetes. Methods The clinical data of 148 T2DM patients was collected and the biochemical indices, including FPG, HbA1c, and LDL-C of these patients, were determined. The diabetic peripheral neuropathy was diagnosed according to the quantitative sensory test (Neurosensory Analyzer Model TSA-Ⅱ) and clinical symptoms. The diabetic cardiovascular autonomic neuropathy was estimated with cardiovascular reflex test and clinical symptoms. Results The prevalence of diabetic peripheral neuropathy was 28% and that of the cardiovascular autonomic neuropathy was 10% . In the patients without diabetic peripheral neuropathy, the prevalence of cardiovascular autonomic neuropathy was 6%, while in those with diabetic peripheral neuropathy, the prevalence of cardiovascular autonomic neuropathy was 21%. Compared with the control group, the disease

  18. Diabetic Neuropathy

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    ... Translational Research Research at NINDS Focus on Research Alzheimer's & Related Dementias Bioengineering Epilepsy Health Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ...

  19. [The significance of quantitative temperature sense thresholds in diagnosis of small fibrous sensory neuropathy in patients with type 2 diabetes].

    Science.gov (United States)

    Yin, Hou-min; Feng, Wei; Ding, Mei-ping

    2015-03-01

    To evaluate the small fiber function in patients with type 2 diabetes mellitus of the early stage by measuring the sensory threshold with the quantitative temperature testing technology. Twenty cases of patients with type 2 diabetes with no neurological deficit (DM group) and twenty age and sex-matched healthy controls underwent the detecting of cold sensory threshold (CST), warm sensory threshold (WST), cold pain threshold (CPT), heat pain threshold (HPT) in both inside of their hands. There was no significant difference in CST, WST, CPT and HPT between left and right inside of hand of the same sample among all the testers. But the four kinds of threshold showed significant difference in the right inside of hand between patients and healthy people ( P threshold can not only reflect increase of the pain threshold value, also can reflect its decrease, i. e. hyperalgesia, which may help to diagnose small fibrous peripheral neuropathy recognition, especially in early diabetic peripheral neuropathy.

  20. Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

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    Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

    2014-09-01

    The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

  1. Reactive Eccrine Syringofibroadenoma Associated with Neuropathy, Venous Stasis, and Diabetic Foot Ulcer

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    Thirawut Sirikham

    2016-06-01

    Full Text Available Eccrine syringofibroadenoma (ESFA is an uncommon benign adnexal neoplasm which derives from cells of the acrosyringium of eccrine sweat glands. The clinical appearance is nonspecific but the histological features are typical. Five clinical subtypes of ESFA exist: (1 solitary ESFA; (2 multiple ESFA associated with ectodermal dysplasia; (3 multiple ESFA without cutaneous features; (4 unilateral linear ESFA (nevoid, and (5 reactive ESFA associated with inflammatory or neoplastic dermatoses. We report the case of a 42-year-old man with long-standing diabetes and neuropathy, presenting with a 4-year history of asymptomatic erythematous plaques on a background of brown hyperpigmentation on the left foot. The clinical presentation and histopathological findings are compatible with reactive ESFA.

  2. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

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    Fatani, Amal Jamil; Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Al-Assaf, Abdullah; Parmar, Mihir Yogeshkumar; Ola, Mohammad Shamsul; Ahmed, Mohammed Mahboobuddin

    2015-05-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  3. Relationship among esophageal dysfunction, diabetic gastro-enteropathy, and autonomic neuropathy

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    Yeh, S.H.; Liu, R.S.; Wu, L.C.; Lin, H.D.; Wang, S.J.; Lin, W.H.

    1985-05-01

    This study assessed the relationship of esophageal radionuclide transit (RT) to diabetic gastroenteropethy (CEP) and autonomic neuropathy (AN). Data were acquired in list mode after an oral dose of 0.5 mCi Tc-99m sulfur colloid in 10 ml of water in the supine position. A modified computer routine was used to calculate: (A) total mean transit time (TMTT) in sec, (B) residual fraction after the first swallow (RF), and )C) retrograde index (RI). Twenty-one patients (pts) with diabetes and 25 normal subjects (N) were studied. Eleven pts belonged to Group 1 with symptomatic GEP and AN; 5, Group 2 with no GEP but with AN; and 5, Group 3 with neither. Abnormal RT mainly occurred in Group 1. RI was the best parameter with respective sensitivity and specificity of 0.91 (10/110 and 0.96 (24/25. RI was abnormal in 10/11 pts with GEP (Group 1), but normal in all 10 pts without GEP (Groups 2 and 3). All 5 pts only with AN (group 2) had normal RI. The authors conclude that esophageal dysfunction is present in nearly all pts with diabetic GEP. However, the presence of AN alone will not explain esophageal transit abnormality.

  4. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

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    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others.

  5. THE INFLUENCE OF PERIPHERAL NEUROPATHY AND PERIPHERAL VASCULAR DISEASE IN THE OUTCOME OF DIABETIC FOOT MANAGEMENT – A PROSPECTIVE STUDY

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    Sundar Prakash S, Krishnakumar, Chandra Prabha

    2015-04-01

    Full Text Available Objective: Peripheral neuropathy and Peripheral Vascular Disease are the risk factors for the development of diabetic foot. The aim of this study was to evaluate differences and predictors of outcome parameters in patients with diabetic foot by stratifying these subjects according to the severity of these risk factors. Materials and methods: This is a prospective study conducted in 70 patients in the age group of 30-90 years diagnosed as Type II Diabetes with foot ulcers. After detailed clinical examination the following tests were conducted in all the patients: Complete blood count (CBC, Haemoglobin (Hb, Random Blood Sugar (RBS, Erythrocyte Sedimentation rate (ESR, Chest X-ray(CXR, Electrocardiography (ECG, foot X-ray, pus culture, Neuropathy testing by Semmes Weinstein Monofilament Test and Vibration Perception Threshold and Peripheral vascularity assessment by Duplex Doppler. Then grading of the ulcers was done using Wagner’s Grade. The outcome of the patients was assessed by recording the healing time, mode of surgery and amputation rates of the patients. Results: A total of 70 patients with diabetic foot were consecutively included into the study (65.7% male, age (31% in 51-60 years, mean diabetes duration (5.2 years, Ulcer Grade (37% in Grade IV, Foot lesions (45.7% in toe, Blood sugar levels (64% in 300-400 mg/dl, Neuropathy (84%, Peripheral vascular disease (67%, major amputation (7% and mortality (1.4%. Conclusion: All diabetic patients should undergo testing for neuropathy and peripheral vascular disease apart from doing other tests.

  6. Cardiovascular autonomic neuropathy contributes to sleep apnea in young and lean type 1 diabetes mellitus patients.

    Science.gov (United States)

    Janovsky, Carolina Castro Porto Silva; Rolim, Luiz Clemente de Souza Pereira; de Sá, João Roberto; Poyares, Dalva; Tufik, Sergio; Silva, Ademir Baptista; Dib, Sergio Atala

    2014-01-01

    Knowledge about association between sleep apnea and cardiovascular autonomic neuropathy (CAN) in type 1 diabetes mellitus (T1DM) might give some insight into the pathogenesis of this condition in these patients. In obese patients, excessive central adiposity, including a large neck circumference, can contribute to obstructive sleep apnea (OSA). Its presence in non-obese patients, however, indicates that it could be correlated with autonomic neuropathy. The aim of this study was to compare the prevalence of OSA in young and lean T1DM patients with and without CAN. We studied 20 adult, non-obese, T1DM patients who were divided into two groups according to the results of the cardiovascular autonomic reflex tests (CARTs). These two groups (9 with CAN and 11 without CAN) were compared to a control group of 22 healthy individuals, who were matched by age and BMI. A polysomnography was performed and sleep was analyzed. The CAN+ group had a significantly higher prevalence of sleep apnea compared to the other groups (67% CAN+; 23% CAN-; 4.5% controls: CAN+ vs. Control; p = 0.006 and CAN+ vs. CAN-; p = 0.02). The CAN- group had higher sleep efficiency compared to the CAN+ group, demonstrating impaired sleep architecture in diabetics with this chronic complication. In conclusion, OSA may be related to the presence of CAN in young and lean T1DM patients. It could contribute to worse the prognosis and reducing the quality of life of these patients without specific treatment of these conditions.

  7. Assessing the quality of reports about randomized controlled trials of acupuncture treatment on Diabetic Peripheral Neuropathy.

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    Chen Bo

    Full Text Available BACKGROUND: To evaluate the reports' qualities which are about randomized controlled trials (RCTs of acupuncture treatment on Diabetic Peripheral Neuropathy (DPN. METHODOLOGY/PRINCIPAL FINDINGS: Eight databases including The Cochrane Library(1993-Sept.,2011, PubMed (1980-Sept., 2011, EMbase (1980-Sept.,2011, SCI Expanded (1998-Sept.,2011, China Biomedicine Database Disc (CBMdisc, 1978-Sept., 2011, China National Knowledge Infrastructure (CNKI, 1979-Sept., 2011 , VIP (a full text issues database of China, 1989-Sept., 2011, Wan Fang (another full text issues database of China 1998-Sept., 2011 were searched systematically. Hand search for further references was conducted. Language was limited to Chinese and English. We identified 75 RCTs that used acupuncture as an intervention and assessed the quality of these reports with the Consolidated Standards for Reporting of Trials statement 2010 (CONSORT2010 and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010(STRICTA2010. 24 articles (32% applied the method of random allocation of sequences. No article gave the description of the mechanism of allocation concealment, no experiment applied the method of blinding. Only one article (1.47% could be identified directly from its title as about the Randomized Controlled Trials, and only 4 articles gave description of the experimental design. No article mentioned the number of cases lost or eliminated. During one experiment, acupuncture syncope led to temporal interruption of the therapy. Two articles (2.94% recorded the number of needles, and 8 articles (11.76% mentioned the depth of needle insertion. None of articles reported the base of calculation of sample size, or has any analysis about the metaphase of an experiment or an explanation of its interruption. One (1.47% mentioned intentional analysis (ITT. CONCLUSIONS/SIGNIFICANCE: The quality of the reports on RCTs of acupuncture for Diabetic Peripheral Neuropathy is moderate to low

  8. Postural control and functional balance in individuals with diabetic peripheral neuropathy

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    Ana Claudia de Souza Fortaleza

    2013-04-01

    Full Text Available Diabetic Peripheral Neuropathy (DPN brings on reduced somatosensation, which can lead to changes in postural control. The objective of this study was to evaluate postural control in a standing position and in different conditions, as well as functional balance in individuals with DPN, make the correlation between the results obtained from the postural control assessment with the values from the functional balance test and compare the results obtained in the neuropathy group with those of the control group, checking for possible differences between the evaluation conditions of both groups. The study included 13 women with DPN (NG and 17 non-diabetic women (CG. Postural control assessment was performed by kinemetry in the following conditions: eyes opened (EO, eyes closed (EC, and semi-tandem (ST. The data was processed in MATLAB and the following variables were generated: mean amplitude of oscillation (MAO in the anterior-posterior (AP and medial-lateral (ML direction; and average speed of oscillation (ASO in AP and ML direction. Functional balance was assessed by the Timed Up and Go Test. There was significant difference between the groups (p≤0.005 in MAO-AP EO and EC, MAO-ML EC and ST, and ASO-ML ST. There were differences between the conditions EO and ST (p≤0.005 and EC and ST (p≤0.005 for the variables MAO-ML and ASO-ML with greater damage to the NG, which also had a lower functional balance (p=0.001. ML instability was positively correlated with functional imbalance. The results show a change in the postural control system in the DPN, which could lead these individuals to a higher risk for falls and functional impairment.

  9. Vasculitic neuropathies.

    Science.gov (United States)

    Gwathmey, Kelly Graham; Burns, Ted Michael; Collins, Michael Paul; Dyck, P James Bonham

    2014-01-01

    The vasculitic neuropathies are a diverse group of disorders characterised by the acute-to-subacute onset of painful sensory and motor deficits that result from inflammatory destruction of nerve blood vessels and subsequent ischaemic injury. They are common in patients with primary systemic vasculitis and are seen in vasculitis secondary to disorders such as rheumatoid arthritis, viral infections, and diabetic inflammatory neuropathies. It is imperative that neurologists recognise these disorders to initiate treatment promptly and thereby prevent morbidity and mortality. To simplify the approach to patients with vasculitis of the peripheral nerves, a straightforward, dichotomous classification scheme can be used in which the vasculitic neuropathies are divided into two groups-nerve large arteriole vasculitis and nerve microvasculitis-on the basis of the size of the involved vessels. The size of the affected blood vessels correlates with the clinical course and prognosis in patients with vasculitic neuropathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy.

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    Yerra, Veera Ganesh; Kalvala, Anil Kumar; Kumar, Ashutosh

    2017-09-01

    Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells. Diabetic rats and high glucose-exposed N2A cells showed reduction in SIRT1 expression with consequent decline in mitochondrial biogenesis and autophagy. ILQ (10 & 20 mg/kg, po) administration to diabetic rats for 2 weeks and exposure to glucose-insulted N2A cells resulted in significant SIRT1 activation with concurrent increase in mitochondrial biogenesis and autophagy. ILQ administration also enhanced NAD(+)/NADH ratio in peripheral sciatic nerves which explains its possible SIRT1 modulatory effect. Functional and behavioural studies show beneficial effect of ILQ as it alleviated nerve conduction and nerve blood flow deficits in diabetic rats along with improvement in behavioural parameters (hyperalgesia and allodynia). ILQ treatment to N2A cells reduced high glucose-driven ROS production and mitochondrial membrane depolarization. Further, ILQ-mediated SIRT1 activation facilitated the Nrf2-directed antioxidant signalling. Overall, results from this study suggest that SIRT1 activation by ILQ mimic effects of calorie restriction, that is, PGC-1α-mediated mitochondrial biogenesis, FOXO3a mediated stress resistance and AMPK mediated autophagy effects to counteract the multiple manifestations in experimental DN. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A successful case on traditional Chinese fumigation-soaking therapy in treating diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    Hongfang Liu; Huayang Wu; Lizhong Zhang; Jinxi Zhao

    2006-01-01

    AIM: To investigate the scheme of inducing the diabetic peripheral neuropathy (DNP) symptoms by combine Chinese traditional medicine with modern medicine. METHODS: Patient hospitalized on April 1, 2005. Main symptoms in hospitalization: His bilateral fingers and toe tips felt stabbing pain, numb, cold, assuming a type of sock set which alleviated after he had a rest and aggravated after exercise. He had also got the symptom of dizziness, asthenia, eating little food, very thin bowel and body pain which had influence on his sleeping. Physical examination in hospital: The bilateral lower limbs which got a hyperpathia did not swell. The bilateral dorsum pedis artery pulsation was atlenuarive. The skin temperature was not high. Other nerve system examination had been discovered abnormal. Diagnosis: Traditional Chinese medical diagnosis: Xiaokebing (blood stasis for insufficiency of qi, blockage of meridian and collaterals). Modern medical diagnosis: Diabetes type 2, DNP, diabetic lower limbs artery obliteration, diabetic foot (0 level), diabetic retinopathy, coronary atherosclerotic heart disease, hypertension, chronic bronchitis, chronic obstructive pulmonary emphysema. Carried on the former therapy plan that continued to use insulin to control blood glucose, depressed blood pressure and total plasma lipoprotein etc. Meanwhile used the therapy of bilateral feet medicinal bath (Sanling 30 g, Ezhu 30 g, Ruxiang 30 g, Moyao 30 g, Zhichuanwu 30 g, Zhicaowu 30 g, Weilingxian 30 g, Mugua 30 g, Sangzhi 30 g), boiled in water, 1 dose everyday, soak feet twice a day, 20-30 minutes once, < 37 ℃. RESULTS: Seven days later, the pain of bilateral feet alleviated obviously, and the bilateral dorsum pedis artery pulsation enhanced. Blood glucose and total plasma lipoprotein had no changes. CONCLUSION: The symptoms of DNP such as pain, coldness, numbness of the lower limbs can be induced by combining feet medicinal bath (fumigation-soaking) treatment with modern medicine.

  12. Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions

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    K. Raafat

    2014-01-01

    Full Text Available Aims. To evaluate the effect of Punica granatum (Pg rind extract and its spray dried biopolymeric dispersions with casein (F1 or chitosan (F2 against Diabetes mellitus (DM and diabetic neuropathy (DN. Methods. We measured the acute (6 h and subacute (8 days effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks. In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.

  13. St. John's Wort seed and feverfew flower extracts relieve painful diabetic neuropathy in a rat model of diabetes.

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    Galeotti, Nicoletta; Maidecchi, Anna; Mattoli, Luisa; Burico, Michela; Ghelardini, Carla

    2014-01-01

    Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes and the few approved therapies for the management of pain have limited efficacy and side effects. With the aim to explore and develop new pharmacological treatments, we investigated the antihyperalgesic properties of St. John's Wort (SJW) and feverfew in streptozotocin (STZ)-diabetic rats. Acute administration of a SJW seed extract reversed mechanical hyperalgesia with a prolonged effect. A SJW extract obtained from the aerial portion of the plant and a feverfew flower extract partially relieved neuropathic pain whereas a feverfew leaf extract was ineffective. The antihyperalgesic efficacy of these herbal drugs was comparable to that of clinically used antihyperalgesic drugs (carbamazepine, lamotrigine, l-acetyl-levocarnitine). Further examinations of SJW and feverfew composition revealed that hyperforin and hypericin might be responsible for the antihyperalgesic properties of SJW whereas the efficacy of feverfew seems to be related to the presence of parthenolide. Rats undergoing treatment with SJW and feverfew did not show any behavioral side effect or sign of altered locomotor activity. Our results suggest that SJW and feverfew extracts may become new therapeutic perspectives for painful DPN.

  14. Assessment of Diabetic Polyneuropathy and Autonomic Neuropathy Using Current Perception Threshold in Korean Patients with Diabetes Mellitus

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    Bo Kyung Koo

    2014-08-01

    Full Text Available BackgroundThe current perception threshold (CPT could be quantified by stimulating Aβ and C fibers at 2,000 and 5 Hz, respectively. C fibers play a role in the autonomic nervous system and are involved in temperature and pain sensation. We evaluated the usefulness of CPT for diagnosing distal polyneuropathy (DPN and cardiovascular autonomic neuropathy (CAN in diabetic patients.MethodsThe CPT was measured in the index finger (C7 level and in the third toe (L5 level in diabetic patients aged 30 to 69 years. We assessed DPN according to the neuropathy total symptom score-6 (NTSS-6 and 10-g monofilament pressure sensation. Subjects with a NTSS-6 >6 or with abnormal 10-g monofilament sensation were defined to have DPN. CAN was evaluated by spectral analysis of heart rate variability and by Ewing's traditional tests.ResultsThe subjects with DPN had significantly higher CPT at all of the frequencies than the subjects without DPN (P6 could be most precisely predicted by CPT at 2,000 and 5 Hz, respectively. However, only 6.5% and 19.6% of subjects with DPN had an abnormal CPT at 2,000 Hz at the C7 and L5 levels. Although CPT at 5 Hz showed a negative correlation with the power of low and high frequency in the spectral analysis (P<0.05, only 16.7% of subjects with CAN exhibited an abnormal CPT at the same frequency.ConclusionAlthough the CPT is significantly associated with neuropathic symptoms or signs corresponding to the nerve fiber stimulated, it provides little additional information compared with conventional evaluations.

  15. [Hereditary neuropathies].

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    Vallat, Jean-Michel; Calvo, Judith; Ghorab, Karima; Tazir, Meriem

    2008-11-15

    Although there are many human hereditary neuropathies, most of them with the exception of Charcot-Marie-Tooth disease or hereditary sensorimotor neuropathy, are rare. Irrespective of their type, the mode of transmission may be autosomal dominant or recessive, or X-linked. The most difficult to diagnose, however, are the sporadic forms. It is customary to distinguish the cases in which the neuropathy is the sole clinical expression from multisystemic diseases where neuropathy is one component of multi-organ involvement. The complexity and the multiplicity of genes involved and the lack of understanding of their exact functions hinder logical presentation of these hereditary neuropathies. For understandable technical reasons, the stage of specific treatment, namely the repair of the mutated gene, has yet to be attained.

  16. Impact of neuropathy on the adherence to diabetes-related self-care activities: a cross-sectional study

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    Timar B

    2016-07-01

    Full Text Available Bogdan Timar,1 Romulus Timar,2 Adalbert Schiller,2 Cristian Oancea,3 Deiana Roman,1 Mihaela Vlad,2 Bogdan Balinisteanu,4 Octavian Mazilu5 1Department of Functional Sciences, 2Second Department of Internal Medicine, 3Department of Infectious Diseases, 4Department of Microscopic Morphology, 5First Department of Surgery, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Purpose: The purpose of this study was to evaluate the impact of the presence and severity of neuropathy and depression on the patient’s adherence to diabetes-related self-care activities (DRSCA in a cohort of patients with type 2 diabetes mellitus (T2DM.Patients and methods: In this cross-sectional, noninterventional study, 198 patients with T2DM were enrolled according to a population-based, consecutive-case enrollment principle. In all patients, the adherence to DRSCA was evaluated using the Summary of Diabetes Self-Care Activities (SDSCA questionnaire; a higher SDSCA score is associated with a better adherence. The presence and severity of neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI and the severity of depression using the Patient Health Questionnaire-9 (PHQ-9.Results: The presence of neuropathy was associated with a decreased SDSCA score (26 points vs 37 points; P<0.001, an increased severe depression prevalence (24.7% vs 4.3%; P<0.001, and an increased PHQ-9 score (12 points vs 7 points; P<0.001. The MNSI score was reverse correlated with SDSCA score (r=-0.527; P<0.001 and positively correlated with PHQ-9 score (r=0.495; P<0.001. The reverse correlation between MNSI score and SDSCA score was present for all the subcomponents of SDSCA questionnaire (diet, exercise, glycemic monitoring, and foot care.Conclusion: The presence of neuropathy is associated with decreases in the quality of adherence to DRSCA in patients with T2DM and with increases in the symptomatology of depression. The significant, negative

  17. Targeting apoptosis signalling kinase-1 (ASK-1 does not prevent the development of neuropathy in streptozotocin-induced diabetic mice.

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    Victoria L Newton

    Full Text Available Apoptosis signal-regulating kinase-1 (ASK1 is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy.

  18. Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

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    Malindu Eranga Fernando

    Full Text Available AIMS: Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. METHODS: Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP and pressure time integral (PTI were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310. RESULTS: Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively. Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p = 0.001. Statistical heterogeneity between studies was moderate. CONCLUSIONS: Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic

  19. Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice.

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    Watcho, Pierre; Stavniichuk, Roman; Tane, Pierre; Shevalye, Hanna; Maksimchyk, Yury; Pacher, Pal; Obrosova, Irina G

    2011-03-01

    We previously reported that PMI-5011, an ethanolic extract of Artemisia dracunculus L., alleviates peripheral neuropathy in high fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and pro-inflammatory changes in the peripheral nervous system. This study evaluated PMI-5011 on established functional, structural, and biochemical changes associated with Type I diabetic peripheral neuropathy. C57Bl6/J mice with streptozotocin-induced diabetes of a 12-week duration, developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia, and intra-epidermal nerve fiber loss. PMI-5011 (500 mg/kg/day for 7 weeks) alleviated diabetes-induced nerve conduction slowing, small sensory nerve fiber dysfunction, and increased intra-epidermal nerve fiber density. PMI-5011 blunted sciatic nerve and spinal cord 12/15-lipoxygenase activation and oxidative-nitrosative stress, without ameliorating hyperglycemia or reducing sciatic nerve sorbitol pathway intermediate accumulation. In conclusion, PMI-5011, a safe and non-toxic botanical extract, may find use in the treatment of diabetic peripheral neuropathy.

  20. Effects of thai foot massage on balance performance in diabetic patients with peripheral neuropathy: a randomized parallel-controlled trial.

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    Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro

    2015-04-20

    BACKGROUND Peripheral neuropathy is the most common complications of diabetic patients and leads to loss of plantar cutaneous sensation, movement perception, and body balance. Thai foot massage is an alternative therapy to improve balance. Therefore, the purpose of this study was to investigate the effects of Thai foot massage on balance performance in diabetic patients with peripheral neuropathy. MATERIAL AND METHODS Sixty patients with type-2 diabetes were recruited and randomly assigned into either the Thai foot massage or control groups. The Thai foot massage group received a modified Thai traditional foot massage for 30 min, 3 days per week for 2 weeks. We measured timed up and go (TUG), one leg stance: OLS), the range of motion (ROM) of the foot, and foot sensation (SWMT) before treatment, after the first single session, and after the 2-week treatment. RESULTS After the single treatment session, only the Thai foot massage group showed a significant improvement in TUG. After the 2-week treatment, both Thai foot massage and control groups showed a significant improvement of TUG and OLS (Pmassage group showed better improvement in TUG than the control group (pmassage group also showed significant improvements in ROM and SWMT after the 2-week treatment. CONCLUSIONS The results of this study suggest that Thai foot massage is a viable alternative treatment for balance performance, ROM of the foot, and the foot sensation in diabetic patients with peripheral neuropathy.

  1. PARP INHIBITION OR GENE DEFICIENCY COUNTERACT INTRAEPIDERMAL NERVE FIBER LOSS AND NEUROPATHIC PAIN IN ADVANCED DIABETIC NEUROPATHY

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    Obrosova, Irina G.; Xu, Weizheng; Lyzogubov, Valeriy V.; Ilnytska, Olga; Mashtalir, Nazar; Vareniuk, Igor; Pavlov, Ivan A.; Zhang, Jie; Slusher, Barbara; Drel, Viktor R.

    2011-01-01

    Evidence for important role of poly(ADP-ribose) polymerase (PARP) activation in diabetic complications is emerging. This study evaluated the role for PARP in rat and mouse models of advanced diabetic neuropathy. The orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one(GPI-15427, formulated as mesilate salt, 30 mg kg−1d−1 in the drinking water, for 10 weeks after first 2 weeks without treatment) at least partially prevented PARP activation in peripheral nerve and DRG neurons, as well as thermal hypoalgesia, mechanical hyperalgesia, tactile allodynia, exaggerated response to formalin, and, the most important, intraepidermal nerve fiber degeneration in streptozotocin-diabetic rats. These findings are consistent with the lack of small sensory nerve fiber dysfunction in diabetic PARP−/− mice. Furthermore, whereas diabetic PARP+/+ mice displayed ~ 46% intraepidermal nerve fiber loss, diabetic PARP−/− preserved completely normal intraepidermal nerve fiber density. In conclusion, PARP activation is an important contributor to intraepidermal nerve fiber degeneration and functional changes associated with advanced Type 1 diabetic neuropathy. The results support the rationale for development of potent and low toxic PARP inhibitors and PARP inhibitor-containing combination therapies. PMID:17976390

  2. Whole-body vibration training improves balance, muscle strength and glycosylated hemoglobin in elderly patients with diabetic neuropathy.

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    Lee, Kyoungjin; Lee, Seungwon; Song, Changho

    2013-12-01

    Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls. However, the information available on how such falls can be prevented is scarce. We investigated the effects of whole-body vibration (WBV) combined with a balance exercise program on balance, muscle strength, and glycosylated hemoglobin (HbA1c) in elderly patients with diabetic peripheral neuropathy. Fifty-five elderly patients with diabetic neuropathy were randomly assigned to WBV with balance exercise group, balance exercise (BE) group, and control group. The WBV and BE groups performed the balance exercise program for 60 min per day, 2 times per week, for 6 weeks. Further, the WBV group performed WBV training (up to 3 × 3 min, 3 times per week, for 6 weeks). The control group did not participate in any training. The main outcome measures were assessed at baseline and after 6 weeks of training; namely, we assessed the postural sway and one leg stance (OLS) for static balance; Berg balance scale (BBS), timed up-and-go (TUG) test, and functional reach test (FRT) for dynamic balance; five-times-sit-to-stand (FTSTS) test for muscle strength; and HbA1c for predicting the progression of diabetes. Significant improvements were noted in the static balance, dynamic balance, muscle strength, and HbA1c in the WBV group, compared to the BE and control groups (P balance exercise program, the short-term WBV therapy is beneficial in improving balance, muscle strength and HbA1c, in elderly patients with diabetic neuropathy who are at high risk for suffering falls.

  3. An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US

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    Zeng, Lily; Alongkronrusmee, Doungkamol; van Rijn, Richard M

    2017-01-01

    Neuropathic pain (NeuP) is a syndrome that results from damaged nerves and/or aberrant regeneration. Common etiologies of neuropathy include chronic illnesses and medication use. Chronic disorders, such as diabetes and alcoholism, can cause neuronal injury and consequently NeuP. Certain medications with antineoplastic effects also carry an exquisitely high risk for neuropathy. These culprits are a few of many that are fueling the NeuP epidemic, which currently affects 7%–10% of the population. It has been estimated that approximately 10% and 7% of US adults carry a diagnosis of diabetes and alcohol disorder, respectively. Despite its pervasiveness, many physicians are unfamiliar with adequate treatment of NeuP, partly due to the few reviews that are available that have integrated basic science and clinical practice. In light of the recent Centers for Disease Control and Prevention guidelines that advise against the routine use of μ-opioid receptor-selective opioids for chronic pain management, such a review is timely. Here, we provide a succinct overview of the etiology and treatment options of diabetic and alcohol- and drug-induced neuropathy, three different and prevalent neuropathies fusing the combined clinical and preclinical pharmacological expertise in NeuP of the authors. We discuss the anatomy of pain and pain transmission, with special attention to key ion channels, receptors, and neurotransmitters. An understanding of pain neurophysiology will lead to a better understanding of the rationale for the effectiveness of current treatment options, and may lead to better diagnostic tools to help distinguish types of neuropathy. We close with a discussion of ongoing research efforts to develop additional treatments for NeuP. PMID:28176937

  4. SUDOSCAN: A Simple, Rapid, and Objective Method with Potential for Screening for Diabetic Peripheral Neuropathy.

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    Dinesh Selvarajah

    Full Text Available Clinical methods of detecting diabetic peripheral neuropathy (DPN are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV] underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs. Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC and calculation of the CAN risk score. Foot ESC (μS was significantly lower in subjects with DPN [n = 24; 53.5(25.1] compared to the No-DPN [77.0(7.9] and HV [77.1(14.3] groups (ANCOVA p<0.001. Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2] and hand [53.5(19.6] ESC compared to No-CAN [foot ESC, 72.1(12.2; hand ESC 64.9(14.4] and HV groups (ANCOVA p<0.001 and 0.001, respectively. ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled.

  5. SUDOSCAN: A Simple, Rapid, and Objective Method with Potential for Screening for Diabetic Peripheral Neuropathy.

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    Selvarajah, Dinesh; Cash, Tom; Davies, Jennifer; Sankar, Adithya; Rao, Ganesh; Grieg, Marni; Pallai, Shillo; Gandhi, Rajiv; Wilkinson, Iain D; Tesfaye, Solomon

    2015-01-01

    Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC) and calculation of the CAN risk score. Foot ESC (μS) was significantly lower in subjects with DPN [n = 24; 53.5(25.1)] compared to the No-DPN [77.0(7.9)] and HV [77.1(14.3)] groups (ANCOVA p<0.001). Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC) was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2)] and hand [53.5(19.6)] ESC compared to No-CAN [foot ESC, 72.1(12.2); hand ESC 64.9(14.4)] and HV groups (ANCOVA p<0.001 and 0.001, respectively). ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled.

  6. Central or peripheral delivery of an adenosine A1 receptor agonist improves mechanical allodynia in a mouse model of painful diabetic neuropathy.

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    Katz, N K; Ryals, J M; Wright, D E

    2015-01-29

    Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8 weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N(6)-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of

  7. Diabetes and nerve damage

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    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  8. Evaluation of diabetic polyneuropathy in Type 2 diabetes mellitus by nerve conduction study and association of severity of neuropathy with serum sFasL level

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    Avijit Mondal

    2012-01-01

    Full Text Available Introduction: Diabetes mellitus (DM, a growing health problem globally, has reached epidemic proportions in India. Recently, Fas-mediated apoptosis has been proposed as a causative factor responsible for neuronal degeneration in diabetic polyneuropathy (DPN, but there are very few studies to show association of serum soluble Fas ligand (sFasL level with severity of neuropathy. Aim and Objective: The aim of this study was to investigate whether serum sFasL, a transmembrane glycoprotein involved in apoptosis, has any association with severity of peripheral neuropathy in Type 2 DM. Materials and Methods: The study was conducted in Department of Physiology in collaboration with Department of Endocrinology, IPGME&R. sFasL levels in serum were assessed using ELISA method in healthy individuals (n = 16, newly diagnosed diabetic controls (n = 16 without any complications, and in DPN cases (n = 33 with predominant neuropathy only. All subjects underwent both electrodiagnostic procedures and vibration perception threshold (VPT for quantitative assessment of the severity of neuropathy. Using nerve conduction studies, amplitudes, velocities, and latencies of both sensory and motor nerves were recorded. Results: In DPN patients, concentration of sFasL levels (87.53 ± 3.49 was significantly decreased (P < 0.0001 not only when compared with normal controls (225.30 ± 2.97 but also when compared with diabetic patients without any complication (161 ± 3.63. Moreover, the concentration of sFasL is significantly (P < 0.0001 associated with the severity of neuropathy both by VPT and nerve conduction velocity (NCV. Conclusion: Fas-mediated apoptosis is involved in Type 2 DM and might be associated with the severity of polyneuropathy.

  9. H-reflex amplitude depression as a marker of presynaptic inhibition in Painful Diabetic Neuropathy (PDN.

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    Ahmad Asmedi

    2016-02-01

    Full Text Available ABSTRACT Painful Diabetic Neuropathy (PDN is a common complication of diabetes mellitus (DM. Disruption in presynaptic inhibition in dorsal horn of the spinal cord has been proposed as one of the pathomechanism of PDN. Previous research showed that presynaptic inhibition can be detected by H-reflex examination. The aim of this study was to know whether the reduction of presynaptic inhibition in spinal dorsal horn of PDN patients really exist, and detectable by H-reflex examination. It was cohort prospective involving 141 (58 men, 83 women patients with DM and impaired glucose tolerance (IGT between the ages of 40 and 61 years from several health facilities in Yogyakarta. All patients underwent clinical, laboratory and electrodiagnostic examination. Demographic, clinical and electrodiagnostic data were collected and analyzed. By survival analysis there were 25 new cases of PDN (12.12% cumulative incidence. Using survival Kaplan Meier analysis, the significant hazard ratio for PDN were 12.81 for median motor nerve amplitude, 5.74 for median nerve distal latency, 3.71 for median sensory nerve amplitude, 6.33 for median sensory latency, 3.4 for tibial nerve amplitude, 3.48 for tibial nerve distal latency, 2.29 for sural nerve amplitude, 4.47 for sural nerve latency, 3.99 for H-reflex latency, 5.88 for H-reflex amplitude, and 17.83 for Diabetic Neuropathy (DN status. Using hazard proportional cox analysis, only H amplitude and DN status (DNS score were significantly correlated with PDN (p= 0.026; hazard ratio = 15.450; CI 95%= 1.39 – 171.62 for H amplitude and p= 0.030; hazard ratio = 10.766; CI 95%=1.26 – 92.09 for DN status. This study showed that depression of H-reflex amplitude was correlated with the occurrence of PDN. This result proves that there was presynaptic inhibition process in PDN that manifests as low H-reflex amplitude.

  10. Shear Stress-Normal Stress (Pressure Ratio Decides Forming Callus in Patients with Diabetic Neuropathy

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    Ayumi Amemiya

    2016-01-01

    Full Text Available Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure ratio (SPR was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure, concretely, peak values (SPR-p and time integral values (SPR-i. The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i.

  11. System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy

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    Mukkamala, R.; Mathias, J. M.; Mullen, T. J.; Cohen, R. J.; Freeman, R.

    1999-01-01

    We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.

  12. Shear Stress-Normal Stress (Pressure) Ratio Decides Forming Callus in Patients with Diabetic Neuropathy

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    Noguchi, Hiroshi; Takehara, Kimie; Ohashi, Yumiko; Suzuki, Ryo; Yamauchi, Toshimasa; Kadowaki, Takashi; Sanada, Hiromi

    2016-01-01

    Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure) and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure) ratio (SPR) was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH) as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure), concretely, peak values (SPR-p) and time integral values (SPR-i). The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i. PMID:28050567

  13. Male accessory gland inflammation prevalence in type 2 diabetic patients with symptoms possibly reflecting autonomic neuropathy

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    Rosita A Condorelli

    2014-10-01

    Full Text Available Male accessory gland inflammation or infection (MAGI is a potentially underdiagnosed complication of type 2 diabetes (DM2; specifically, we reported in a recent study that the frequency of MAGI was 43% among DM2 patients. In previous studies, we have demonstrated that diabetic autonomic neuropathy (DAN is associated with a peculiar ultrasound characterization of the seminal vesicles (SVs in DM2 patients. The aim of the present study was to evaluate the frequency of MAGI in two different categories of DM2 patients (i.e. patients with and without symptoms that possibly reflect DAN and the respective ultrasound characterizations. Sixty DM2 patients with a mean (± s.e.m. age of 42.0 ± 6.0 years (range: 34-47 years were classified according to the presence or the absence of symptoms that could possibly reflect DAN (group A: DM2 with symptoms possibly reflecting DAN, n = 28 patients and group B: DM2 without symptoms possibly reflecting DAN, n = 32 patients. The patients in Group A exhibited a significantly higher frequency of MAGI compared with those in group B patients (P < 0.05; moreover, the Group A patients exhibited a significantly higher frequency of ultrasound signs suggestive of vesiculitis (P < 0.05. Finally, the concentrations of lymphocytes but not the concentrations of the leukocytes in the semen were significantly higher (P < 0.05 in group A compared with group B.

  14. Identifying diabetic patients with cardiac autonomic neuropathy by heart rate complexity analysis

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    Palaniswami Marimuthu

    2009-01-01

    Full Text Available Abstract Background Cardiac autonomic neuropathy (CAN in diabetes has been called a "silent killer", because so few patients realize that they suffer from it, and yet its effect can be lethal. Early sub clinical detection of CAN and intervention are of prime importance for risk stratification in preventing sudden death due to silent myocardial infarction. This study presents the usefulness of heart rate variability (HRV and complexity analyses from short term ECG recordings as a screening tool for CAN. Methods A total of 17 sets of ECG recordings during supine rest were acquired from diabetic subjects with CAN (CAN+ and without CAN (CAN- and analyzed. Poincaré plot indexes as well as traditional time and frequency, and the sample entropy (SampEn measure were used for analyzing variability (short and long term and complexity of HRV respectively. Results Reduced (p > 0.05_Poincaré plot patterns and lower (p Conclusion Our results demonstrate the potential utility of SampEn (a complexity based estimator of HRV in identifying asymptomatic CAN.

  15. Assessment of diabetic neuropathy with emission tomography and magnetic resonance spectroscopy.

    Science.gov (United States)

    Rao, Harshvardhan; Gaur, Neeraj; Tipre, Dnyanesh

    2017-04-01

    Diabetic neuropathies (DNs) are nerve-damaging disorders associated with diabetes. They are commonly attributed to peripheral nerves and primarily affect the limbs of the patient. They cause altered sensitivity to external stimuli along with loss in balance and reflexes of the affected patient. DNs are associated with a variety of clinical manifestations including autonomic failure and are caused by poor management of blood sugar levels. Imaging modalities provide vital information about early physiological changes in DNs. This review summarizes contributions by various teams of scientists in developing imaging methods to assess physiological changes in DNs and ongoing clinical trials where imaging modalities are applied to evaluate therapeutic intervention in DNs. Development of PET, single photon emission computed tomography, and magnetic resonance spectroscopy methods over the past 20 years are reviewed in the diagnostic assessment of DNs. Abnormal radiotracer pharmacokinetics and neurometabolite spectra in affected organs confirm physiological abnormalities in DN. With the use of the Siemens Biograph mMR and GE Signa - 60 cm (PET/MRI scanner), simultaneous acquisition of physiological and anatomical information could enhance understanding of DNs and accelerate drug development.

  16. Partial Replacement with Menhaden Oil Improves Peripheral Neuropathy in High-Fat-Fed Low-Dose Streptozotocin Type 2 Diabetic Rat

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    Coppey, Lawrence J.; Amey Holmes; Davidson, Eric P.; Yorek, Mark A.

    2012-01-01

    Aims. To determine the effect of partial replacement of a high-fat diet with menhaden oil on diabetic neuropathy in an animal model of type 2 diabetes. Materials and Methods. High-fat/low-dose streptozotocin diabetic rats were used to examine the influence of replacing 50% of the source of the high-fat diet (lard) with menhaden oil, a natural source of n-3 fatty acids, on diabetic neuropathy. Endpoints included analyses of glucose tolerance, fatty liver disease, serum and liver fatty acid com...

  17. Prevalence and risk factors for peripheral neuropathy among type 2 diabetes mellitus patients at a tertiary care hospital in coastal Karnataka

    Directory of Open Access Journals (Sweden)

    Sonalika Gogia

    2017-01-01

    Full Text Available Context and Objective: In view of the growing burden of type 2 diabetes mellitus (T2DM globally and associated microvascular and macrovascular complications, the study was done to assess the prevalence and risk factors for diabetic neuropathy among T2DM patients attending a tertiary care hospital. Subjects and Methods: T2DM patients' ≥30 years of both gender, presenting to the Medicine Department at a tertiary care hospital were included in the study. Diabetic Neuropathy Symptom (DNS questionnaire to assess symptoms and Diabetic Neuropathy Examination (DNE scoring to assess clinical signs were used. Results: A total of 273 patients were included. The mean age was 57.8 ± 11.5 years. The male to female distribution was 75% (202 and 25% (71, respectively. According to DNS instrument, 41.4% patients scored positive for the presence of neuropathy while only 24.5% had neuropathy according to DNE score. The proportion of males affected by neuropathy was more than females. 43.1% males had a positive DNS score while only 27.2% of them had a positive DNE score. Duration of the disease was positively correlated with neuropathy. Neuropathy was more prevalent among people who had higher systolic and diastolic blood pressure as per DNS and DNE instruments. Conclusions: The present study identified a higher proportion of males to be affected by neuropathy. Hence, more detailed evaluation must be accorded to elderly male diabetic patients with longer duration of the disease. Lifestyle modifications and watchful screening need to be incorporated as part of routine patient health education during follow-up clinic visits.

  18. North America and South America (NA-SA) neuropathy project.

    Science.gov (United States)

    Pasnoor, Mamatha; Nascimento, Osvaldo J M; Trivedi, Jaya; Wolfe, Gil I; Nations, Sharon; Herbelin, Laura; de Freitas, M G; Quintanilha, Giseli; Khan, Saud; Dimachkie, Mazen; Barohn, Richard

    2013-08-01

    Peripheral neuropathy is a common neurological disorder. There may be important differences and similarities in the diagnosis of peripheral neuropathy between North America (NA) and South America (SA). Neuromuscular databases were searched for neuropathy diagnosis at two North American sites, University of Kansas Medical Center and University of Texas Southwestern Medical Center, and one South American site, Federal Fluminense University in Brazil. All patients were included into one of the six major categories: immune-mediated, diabetic, hereditary, infectious/inflammatory, systemic/metabolic/toxic (not diabetic) and cryptogenic. A comparison of the number of patients in each category was made between North America and South America databases. Total number of cases in North America was 1090 and in South America was 1034 [immune-mediated: NA 215 (19.7%), SA 191 (18%); diabetic: NA 148 (13.5%), SA 236 (23%); hereditary: NA 292 (26.7%), SA 103 (10%); infectious/inflammatory: NA 53 (4.8%), SA 141 (14%); systemic/metabolic/toxic: NA 71 (6.5%), SA 124 (12%); cryptogenic: NA 311 (28.5%), SA 239 (23%)]. Some specific neuropathy comparisons were hereditary neuropathies [Charcot-Marie-Tooth (CMT) cases] in NA 246/292 (84.2%) and SA 60/103 (58%); familial amyloid neuropathy in SA 31/103 (30%) and none in NA. Among infectious neuropathies, cases of human T-lymphotropic virus type 1 (HTLV-1) neuropathy in SA were 36/141(25%), Chagas disease in SA were 13/141(9%) and none for either in NA; cases of neuropathy due to leprosy in NA were 26/53 (49%) and in SA were 39/141(28%). South American tertiary care centers are more likely to see patients with infectious, diabetic and hereditary disorders such as familial amyloid neuropathies. North American tertiary centers are more likely to see patients with CMT. Immune neuropathies and cryptogenic neuropathies were seen equally in North America and South America.

  19. Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration.

    Science.gov (United States)

    Landowski, Lila M; Dyck, P James B; Engelstad, JaNean; Taylor, Bruce V

    2016-10-01

    Peripheral neuropathies (PNs) are injuries or diseases of the nerves which arise from varied aetiology, including metabolic disease, trauma and drug toxicity. The clinical presentation depends on the type of neuropathy, and may include the loss of motor, sensory and autonomic functions, or development of debilitating neuropathic pain distal to the injury site. It can be challenging to identify the aetiology of PNs, as the clinical syndromes are often indistinct. However, the mechanisms that underlie pathological changes in peripheral neuropathy are fundamentally different, depending on the trigger. This review focuses on the axonopathy observed in two frequently encountered forms of peripheral neuropathy, diabetic neuropathy and chemotherapy-induced neuropathy. A key manifestation of axonopathy in PN is the degeneration of terminal arbors of peripheral nerves, resulting in a loss of epidermal nerve fibres and inappropriate termination of nerve endings. Many symptoms of PN arise from aberrant termination of nerve endings, and the underlying axonopathy may be non-reversible, as nerve regeneration after injury and disease is often poor, absent, or aberrant. Directed guidance of terminal arbors back into the epidermis is therefore a suggested approach to treat peripheral neuropathy. This review will outline potential strategies to enhance and guide axonal regeneration and reinnervation in the skin. Using diabetic neuropathy and chemotherapy-induced neuropathy as specific examples, this review examines the setbacks encountered with the translation of growth factors into therapeutics for human neuropathy, and suggests a number of approaches for topical drug delivery.

  20. Peripheral diabetic neuropathy or restless legs syndrome in persons with type 2 diabetes mellitus: Differentiating diagnosis in practice.

    Science.gov (United States)

    Cuellar, Norma G; Dorn, James Mark

    2015-12-01

    Restless legs syndrome (RLS) affects 8% of the population and is identified in 21% of individuals with type 2 diabetes (T2DM). Symptoms of RLS manifest as discomfort in the legs (e.g., numbness, tingling, electrical stimulations), usually occurring at night or at rest (sitting or lying), resulting in the need to move the legs. Peripheral diabetic neuropathy (PDN), which has symptoms similar to RLS, is a common consequence of T2DM. The purpose of this article is to provide nurse practitioners (NPs) with (a) an overview of RLS, (b) the association of RLS with T2DM, (c) the defining characteristics that differentiate PDN from RLS, and (d) implications to improve health outcomes of persons with T2DM. The literature was reviewed for the most current data on RLS and the defining characteristics of PDN. PDN is a common consequence of T2DM and is described as numbness, tingling, or discomfort in the lower extremities, symptoms that are similar to RLS. Differentiating the symptoms of PDN and RLS may be confusing and result in misdiagnoses, lack of treatment, and poor outcomes. It is essential that NPs are knowledgeable about the diagnostic and defining features of RLS as well as the characteristics of other conditions, specifically PDN, which mimics RLS. ©2015 American Association of Nurse Practitioners.

  1. Study progression of painful diabetic neuropathy%糖尿病痛性神经病变的研究进展

    Institute of Scientific and Technical Information of China (English)

    金星

    2013-01-01

    糖尿病痛性神经病变(painful diabetic neuropathy,PDN)是一种感觉性周围神经病变.糖尿病神经病变的疼痛机制与初级感觉神经元和外周轴突通路的损伤产生过度兴奋和自发的异常放电相关.文中就PDN的病理机制、诊治进展进行综述.%Painful diabetic neuropathy (PDN) is a kind of sensory peripheral neuropathy. Hyperexcitability and aberrant spontaneous impulse generation by damaged first -order sensory neurons and their peripheral axons are well -established processes that strongly contribute to pain associated with diabetic neuropathy . This review describes the pathological mechanism , progression of diagnose and treatment of PDN.

  2. Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats.

    Science.gov (United States)

    Hernández-Pedro, Norma; Granados-Soto, Vinicio; Ordoñez, Graciela; Pineda, Benjamin; Rangel-López, Edgar; Salazar-Ramiro, Aleli; Arrieta, Oscar; Sotelo, Julio

    2014-09-01

    All-trans retinoic acid (ATRA) promotes the endogenous expression of both nerve growth factor (NGF) and retinoic acid receptor beta (RAR-β). We have previously shown that the administration of ATRA partly reverts the damage induced by diabetic neuropathy (DN). In this investigation, we evaluated the effects of vitamin A, a commercial, inexpensive compound of retinoic acid, on the therapy of DN. A total of 70 rats were randomized into 4 groups. Group A was the control, and groups B, C, and D received a total dose of 60 mg/kg streptozotocin intraperitoneally. When signs of DN developed, groups C and D were treated either with vitamin A (20,000 IU) or with ATRA 25 mg/kg for 60 days. Plasma glucose, contents of NGF, thermal and nociceptive tests, and RAR-β expression were evaluated. All diabetic rats developed neuropathy. The treatment with vitamin A and ATRA reverted similarly the sensorial disturbances, which was associated with increased contents of NGF and RAR-β expression. Our results indicate that the administration of vitamin A has the same therapeutic effect as ATRA on peripheral neuropathy and suggest its potential therapeutic use in patients with diabetes.

  3. Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Negi, Geeta; Kumar, Ashutosh [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India); Sharma, Shyam S., E-mail: sssharma@niper.ac.in [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India)

    2010-01-01

    Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

  4. Altered neurotrophism in diabetic neuropathy: spelunking the caves of peripheral nerve.

    Science.gov (United States)

    Dobrowsky, Rick T; Rouen, Shefali; Yu, Cuijuan

    2005-05-01

    Diabetic peripheral neuropathy (DPN) is a frequent and potentially traumatic complication in diabetic individuals. The chronic nature of diabetes and its associated hyperglycemic episodes initiate a complex and inter-related series of metabolic and vascular insults that contribute to the polygenic etiology of DPN. One contributing factor in DPN is an altered neurotrophism that results from changes in the synthesis and expression of neurotrophins, insulin-like growth factor, and various cytokine-like growth factors that can directly act upon distinct subpopulations of sensory and motor neurons. Although considerable effort has focused upon examining growth factor signaling in hyperglycemically stressed neurons, myelin-forming Schwann cells also undergo substantial degenerative changes in DPN. However, scant attention has been devoted to understanding the effect of hyperglycemia on the response of Schwann cells to growth factors critical to their function. Neuregulins are gliotrophic growth factors that signal through members of the Erb B receptor-tyrosine kinase family. The neuregulin/Erb B ligand-receptor cassette can differentially influence the response of Schwann cells throughout their development by regulating cell survival, mitogenesis, and differentiation. The activity of Erb B receptors may also be affected by their interaction with caveolin-1, a protein marker of caveolae ("little caves"). However, whether neuregulin signaling may be directly or indirectly altered under conditions of hyperglycemic stress and contribute to the physiological progression of DPN is unknown. This brief review will provide a perspective on a putative role of changes in the caveolar proteome of Schwann cells in contributing to an "altered neuregulinism" in DPN.

  5. Clinical Observation of Diabetic Peripheral Neuropathy Treated by Moxibustion plus Mecobalamin

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-feng; XIAO Yuan-chun

    2008-01-01

    Objective: To evaluate the clinical efficacy of moxibustion plus Mecobalamin in treating diabetic peripheral neuropathy. Methods: Eighty subjects were equally allocated into combination and control groups. On the basis of the same basic treatment, the combination group was treated by moxibustion plus Mecobalamin and the control group simply by Mecobalamin. Treatment lasted 3 months. Nerve conduction velocity and symptom severity were compared between pre-treatment and post-treatment. Results: Nerve conduction velocity was improved in both combination and control groups and more obviously in the combination group. The marked effective rate, effective rate and ineffective rate were respectively 52.5%, 32.5% and 15.0% in the combination group and 35.0%, 27.5% and 37.5% in the control group. There were statistically significant differences between the two groups (P<0.01 or P<0.05). Conclusion: Based on a basic treatment, moxibustion plus Mecobalamin is superior to simple Mecobalamin in treating diabetic peripheral neuropathy.%目的:评价艾灸联合弥可保治疗糖尿病周围神经病变的疗效.方法:对糖尿病周围神经病变患者80例按1:1比例等分为联合组和对照组,两组基于等同的基础治疗之上,联合组用艾灸联合弥可保治疗,对照组单纯用弥可保治疗,疗程3个月,比较治疗前后的神经传导速度变化和症状改善情况.结果:联合组和对照组神经传导速度均改善,以联合组改善更明显;联合组和对照组显效、有效、无效分别是52.5%、32.5%、15.0%和35.0%、27.5%、37.5%,组间差异有统计学意义(P<0.01或P<0.05).结论:建立于基础治疗之上的艾灸联合弥可保治疗糖尿病周围神经病变优于单纯弥可保治疗.

  6. Association of patient-rated severity with other outcomes in patients with painful diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Taylor-Stokes G

    2011-12-01

    Full Text Available Gavin Taylor-Stokes1, James Pike1, Alesia Sadosky2, Arthi Chandran2, Thomas Toelle31Adelphi Real World, Adelphi Mill, Bollington, Macclesfield, Cheshire, UK; 2Pfizer Inc, New York, NY, USA; 3Department of Neurology, Technische Universität München, Munich, GermanyObjective: To evaluate the association of patient-reported severity of painful diabetic peripheral neuropathy (pDPN with other outcomes in a European population of patients using the Adelphi Disease Specific Programme for pDPN (DSP III, 2008.Methods: The severity of patients' pDPN (mild, moderate, or severe was rated independently by both patients and physicians. Relationships were evaluated between patient-reported pDPN severity and other patient-reported outcomes including pain, sleep, function, and work productivity. Physicians rated the severity of patients’ pDPN (1 = mild, 2 = moderate, 3 = severe and sleep interference.Results: Patient-reported data were available from 634 individuals (56.2% male, mean age 63 years from France, Germany, Italy, and the UK, of whom only 22.2% reported that they were currently employed. pDPN severity was rated as mild, moderate, and severe by 22.2%, 60.9%, and 16.9% of the patients, respectively. There was a significant association between patient-rated and physician-rated pDPN severity (P < 0.0001, although there were discrepancies in agreement (kappa = 0.37, 95% confidence interval [CI] 0.31, 0.43; weighted kappa = 0.43, 95% CI 0.37, 0.48 among physician and patient ratings in a substantial proportion of patients across severity categories. Higher pDPN severity was associated with greater interference of daily function including sleep (P < 0.0001 for all pairwise comparisons. Among employed patients, percent of pDPN-related impairment while at work (presenteeism and overall work impairment increased with greater pDPN severity, resulting in indirect costs that increased significantly with pDPN severity; $8266, $15,449, and $24,300 for mild

  7. Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy

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    Allen R

    2014-06-01

    Full Text Available Rob Allen,1 Uma Sharma,2 Suna Barlas31Formerly of Pfizer Inc, Collegeville, Pennsylvania, PA, USA; 2MMS Holdings Inc, Canton, MI, USA; 3Pfizer Inc, Collegeville, Pennsylvania, PA, USAPurpose: To assess the safety and efficacy of the serotonin–norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN.ClinicalTrials.gov identifiers: NCT00283842, NCT01050218.Patients and methods: This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study.Results: A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; P<0.001 and 400 mg groups (0.91 [95% CI: 0.23 to 1.59]; P=0.027; differences from placebo were not statistically significant for the 50 mg (0.58 [95% CI: –0.08 to 1.25] and 100 mg (0.59 [95% CI: –0.03 to 1.21] groups. Nausea and dizziness were the most common treatment-emergent adverse events reported in the short-term study, and the most common adverse events leading to discontinuation in the short-term study and the extension. Adverse events rates were dose-dependent in the short-term studies.Conclusion: Desvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at

  8. Advances in the pathogenesis of diabetic peripheral neuropathy%糖尿病周围神经病变发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    董琪; 李全民

    2015-01-01

    糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)为糖尿病最常见慢性并发症之一,发病率为10%~90%,通常累及患者感觉、运动以及自主神经,严重影响患者日常生活。研究糖尿病周围神经病变的相关机制,可为治疗方向探索提供思路。本文就糖尿病周围神经病变发病机制搜集近年相关文献,相关进展综述如下。%As one of the most common chronic complications of diabetes, diabetic peripheral neuropathy (DPN)usually involves patients with their sensory, motor and autonomic.The incidence rate of the disease is 10% to 90%.Diabetic peripheral neuropathy seriously affect the patient’s daily life.Therefore, it is particularly important to study the mechanisms of diabetic peripheral neuropathy, in order to provide more direction and ideas for treatment. This paper collected the literature on the pathogenesis of diabetic peripheral neuropathy in recent years, related developments are summarized below.

  9. Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy:a meta-analysis of 16 randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    Bing Pang; Tian-yu Zhao; Lin-hua Zhao; Fang Wan; Ru Ye; Qiang Zhou; Feng Tian; Xiao-lin Tong

    2016-01-01

    OBJECTIVE:This meta-analysis was performed to systematically assess the efifcacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction (HGWWD) for treating diabetic peripheral neuropathy. DATA SOURCES:Six electronic databases, including the Cochrane Library, MEDLINE database, Chinese Biomedical Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journals Database, and the Wanfang Database, were search ed on the internet for randomized controlled trials published up until 1 December 2015. The search terms included“Chinese herbal medi-cine”,“diabetic peripheral neuropathy”and“randomized controlled trials”in Chinese and in English. DATA SELECTION:We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group, without restriction for the control group. We assessed literature quality in accordance with the Cochrane Review Handbook. A random or a ifxed effects model was used to analyze outcomes using RevMan 5.2 software. OUTCOME MEASURES:The primary outcomes were changes in symptoms and nerve conduction velocities. The secondary outcomes were fasting blood glucose and hemorheological indexes. RESULTS:Sixteen randomized controlled trials, with a total of 1,173 patients, were included. Meta-analysis revealed that the efifcacy of HGWWD for diabetic peripheral neuropathy was signiifcantly superior compared with the control treatment (i.e., control group) (risk ratio=0.36, 95%conifdence interval (CI):0.29–0.46, Z=8.33, P CONCLUSION:HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities. Our study suggests that HGWWD may have signiifcant therapeutic efifcacy for the treatment of diabetic peripheral neuropathy. However, the meth-odological quality of the randomized controlled trials was generally low. Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

  10. Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Michela M Taiana

    Full Text Available The pathogenetic role of vascular endothelial growth factor (VEGF in long-term retinal and kidney complications of diabetes has been demonstrated. Conversely, little is known in diabetic neuropathy. We examined the modulation of VEGF pathway at mRNA and protein level on dorsal root ganglion (DRG neurons and Schwann cells (SC induced by hyperglycaemia. Moreover, we studied the effects of VEGF neutralization on hyperglycemic DRG neurons and streptozotocin-induced diabetic neuropathy. Our findings demonstrated that DRG neurons were not affected by the direct exposition to hyperglycaemia, whereas showed an impairment of neurite outgrowth ability when exposed to the medium of SC cultured in hyperglycaemia. This was mediated by an altered regulation of VEGF and FLT-1 receptors. Hyperglycaemia increased VEGF and FLT-1 mRNA without changing their intracellular protein levels in DRG neurons, decreased intracellular and secreted protein levels without changing mRNA level in SC, while reduced the expression of the soluble receptor sFLT-1 both in DRG neurons and SC. Bevacizumab, a molecule that inhibits VEGF activity preventing the interaction with its receptors, restored neurite outgrowth and normalized FLT-1 mRNA and protein levels in co-cultures. In diabetic rats, it both prevented and restored nerve conduction velocity and nociceptive thresholds. We demonstrated that hyperglycaemia early affected neurite outgrowth through the impairment of SC-derived VEGF/FLT-1 signaling and that the neutralization of SC-secreted VEGF was protective both in vitro and in vivo models of diabetic neuropathy.

  11. Quantification of Acupuncture Effects on Peripheral Neuropathy of Unknown and Diabetic Cause by Nerve Conduction Studies

    Institute of Scientific and Technical Information of China (English)

    Sven Schroeder; Andrew Remppis; Tobias Greten; Frank Brazkiewicz; Michael Morcos; Henry Johannes Greten

    2008-01-01

    目的:通过神经传导改变的测量评估针灸对于周围神经病变的疗效.方法:评估192例周围神经病变患者一年以上.17例为糖尿病神经病变,其中3例根据海德堡中医规范定义接受传统中医的针灸治疗,所有神经传导检测均得到改善.14例非特异性治疗的患者,3例(21.4%)患者神经传导检测显示改善,其余11例(78.6%)患者神经传导检测显示恶化.全部47例患者符合周围神经病变不明确病因学的标准,21例患者接受针灸治疗,26例患者接受非特异性治疗.所有组别均在治疗前和4月后进行神经传导检测.结果:1)糖尿病神经病变,对照组中3例患者得到改善,11例显示恶化,组间比较有显著差异.2)周围神经病变, 针灸组中16例患者(76.2%)得到改善,而在对照组中只有4例(15.4%)得到改善.针灸组中3例患者(14.3%)显示无变化,2例(9.5%)显示恶化.但是对照组中7例(26.9%)无变化,并有15例(57.7%)显示恶化.具有显著差异.结论:根据神经传导检测,针灸治疗周围神经病变具有积极的疗效.%Objective: To evaluate the effect of acupuncture on peripheral neuropathy (PN) as measured by changes in nerve conduction studies (NCS). Methods: 192 patients with PN were evaluated over a period of 1 year. In 17 patients diabetic neuropathy was found. 3 of these patients received acupuncture therapy according to classical Chinese medicine as defined by the Heidelberg model of TCM and all improved in NCS. Of the 14 non-specifically treated patients, 3 (21.4%) presented with improved NCS and 11 (78.6%) aggravated in NCS (P<0.03). An overall of 47 patients met the criteria for PN of undefined aetioiogy, 21 patients received acupuncture therapy, while 26 patients received no specific treatment. All groups were examined by NCS before treatment and 4 months later. Results: 1) Diabetic neuropathy, in the control-group 3 patients improved and 11 showed an aggravation. Comparison of groups was

  12. Rufinamide Improves Functional and Behavioral Deficits via Blockade of Tetrodotoxin-Resistant Sodium Channels in Diabetic Neuropathy.

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    Kharatmal, Shivsharan B; Singh, Jitendra N; Sharma, Shyam S

    2015-01-01

    Rufinamide is a structurally novel, antiepileptic drug approved for the treatment of Lennox-Gastaut syndrome. Its mechanism of action involves inhibition of voltage-gated Na+ channels (VGSCs) with possible membrane-stabilizing effects. VGSCs play a significant role in the pathogenesis of neuropathic pain. Therefore, we investigated the effects of rufinamide on tetrodotoxin-resistant sodium current (TTX-R I(Na)) in acutely dissociated rat dorsal root ganglion (DRG) neurons isolated from streptozotocin-induced diabetic rats by using whole-cell voltage-clamp configuration. In addition, the functional and behavioural nociceptive parameters were evaluated to assess its potential in diabetic neuropathy. Diabetic rats demonstrated the mechanical allodynia and thermal hyperalgesia with reduced nerve perfusion and conduction velocity as compared to control. Rufinamide treatments (3 and 10 mg/kg) significantly improved these functional and nociceptive deficits. Diabetic rat DRG neurons exhibited increased TTX-R I(Na) density as compared to control. The voltage-dependent activation and steady-state inactivation curves for TTX-R I(Na) in DRG neurons from diabetic rats were shifted negatively as compared to control. Rufinamide treatments significantly blocked the TTX-R Na+ channel activity as evident from significant reduction in I(Na) density and hyperpolarizing shift in activation and inactivation curves as compared to diabetic control. This suggests that rufinamide acts on TTX-R Na+ channels, reduces channel activity and attenuates nerve functional and behavioral parameters in diabetic rats. Altogether, these results indicate therapeutic potential of rufinamide in the treatment of diabetic neuropathy.

  13. Diabetic peripheral neuropathy in ambulatory patients with type 2 diabetes in a general hospital in a middle income country: a cross-sectional study.

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    María de Los Angeles Lazo

    Full Text Available AIM: We aimed to estimate the morbidity rate and associated factors for diabetic peripheral neuropathy (DPN in a low-middle income country setting. METHODS: Cross-sectional study, data was gathered at Peru's Ministry of Health national specialized hospital for endocrinological conditions through standardized interviews, anthropometric measurements and blood tests for glycated haemoglobin (HbA1c. DPN was evaluated using two techniques: the Semmes-Weinstein monofilament test and the diabetic neuropathy symptom score. Overall prevalence and 95% confidence intervals (95% CI were calculated. Potential factors related to DPN explored included body mass index, years with disease (<10 vs. ≥10 years, glycaemic control (HbA1c <7% vs. ≥7%, microalbuminuria, retinopathy, and current pharmacological treatment. Multivariable analysis was performed using Poisson analysis to calculate prevalence ratios. RESULTS: DPN was observed in 73/129 (56.6% patients. In multivariable analysis adjusted by age and sex, the prevalence ratio of neuropathy was 1.4 times higher (95% CI 1.07-1.88 in patients who took insulin plus metformin compared to patients who used one treatment alone, and 1.4 higher (95% CI 1.02-1.93 in patients with ≥10 years of disease compared to those with a shorter duration of disease. Also we found some characteristics in foot evaluation associated to neuropathy such as deformities (p<0.001, onychomycosis (p = 0.012, abnormal Achilles reflex (p<0.001, pain perception (p<0.001 and vibration perception (p<0.001. CONCLUSION: DPN is highly frequent among patients with diabetes in a national specialized facility from Peru. Associated factors to DPN included being a diabetic patient for over ten years, and receiving insulin plus metformin.

  14. Prevalence in the Italian regions of pain in patients with diabetic peripheral neuropathy (NDP and the current costs of drug treatment for principals with specific indication

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    Luca Guidi

    2010-03-01

    Full Text Available The present analysis estimates the prevalence of pain in patients affected by peripheral diabetic neuropathy referring to Italian and English data published recently and the cost of pharmacological treatments related to specifically indicated drugs. 16% of diabetic patients in Italy is affected by pain symptoms during PDN (peripheral diabetic neuropathy. The corresponding prevalence is 425,168 cases annually. A little number of these patients is actually treated with specifically indicated drugs (duloxetine, pregabalin and gabapentin, anyway the increase of share of duloxetine treatments would take to significant savings due to its lower costs among the specifically indicated pharmacological options.

  15. Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis.

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    Mu, Ze-Peng; Wang, Yan-Gang; Li, Cheng-Qian; Lv, Wen-Shan; Wang, Bin; Jing, Zhao-Hai; Song, Xue-Jia; Lun, Yu; Qiu, Ming-Yue; Ma, Xiao-Long

    2017-03-01

    Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD] = 1.203, 95 % CI 0.795-1.611, P diabetic patients with DPN when compared with healthy controls (SMD = 2.364, 95 % CI 1.333-3.394, P diabetes (odds ratio [OR] = 2.594, 95 % CI 1.182-5.500, P = 0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR = 2.486, 95 % CI 0.672-9.193, P = 0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.

  16. Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy

    Science.gov (United States)

    Allen, Rob; Sharma, Uma; Barlas, Suna

    2014-01-01

    Purpose To assess the safety and efficacy of the serotonin–norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN). ClinicalTrials.gov identifiers NCT00283842, NCT01050218. Patients and methods This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS) score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study. Results A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; PDesvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at all doses assessed. Desvenlafaxine was generally well-tolerated in the short-term and long-term studies. PMID:25018648

  17. Multi-joint foot kinetics during walking in people with Diabetes Mellitus and peripheral neuropathy.

    Science.gov (United States)

    DiLiberto, Frank E; Tome, Josh; Baumhauer, Judith F; Quinn, Jill R; Houck, Jeff; Nawoczenski, Deborah A

    2015-10-15

    Neuropathic tissue changes can alter muscle function and are a primary reason for foot pathologies in people with Diabetes Mellitus and peripheral neuropathy (DMPN). Understanding of foot kinetics in people with DMPN is derived from single-segment foot modeling approaches. This approach, however, does not provide insight into midfoot power and work. Gaining an understanding of midfoot kinetics in people with DMPN prior to deformity or ulceration may help link foot biomechanics to anticipated pathologies in the midfoot and forefoot. The purpose of this study was to evaluate midfoot (MF) and rearfoot (RF) power and work in people with DMPN and a healthy matched control group. Thirty people participated (15 DMPN and 15 Controls). An electro-magnetic tracking system and force plate were used to record multi-segment foot kinematics and ground reaction forces during walking. MF and RF power, work, and negative work ratios were calculated and compared between groups. Findings demonstrated that the DMPN group had greater negative peak power and reduced positive peak power at the MF and RF (all p≤0.05). DMPN group negative work ratios were also greater at the MF and RF [Mean difference MF: 9.9%; p=0.24 and RF: 18.8%; pstudy is recommended to determine how both MF and RF kinetics influence the development of deformity and ulceration in people with DMPN.

  18. Individual metatarsal and forefoot kinematics during walking in people with diabetes mellitus and peripheral neuropathy.

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    DiLiberto, Frank E; Tome, Josh; Baumhauer, Judith F; Houck, Jeff; Nawoczenski, Deborah A

    2015-10-01

    The purpose of this study was to compare in-vivo kinematic angular excursions of individual metatarsal segments and a unified forefoot segment in people with Diabetes Mellitus and peripheral neuropathy (DMPN) without deformity or ulceration to a healthy matched control group. Thirty subjects were recruited. A five- segment foot model (1st, 3rd, and 5th metatarsals, calcaneus, tibia) was used to examine relative 3D angular excursions during the terminal stance phase of walking. Student t-tests were used to assess group differences in kinematics. Pearson correlations and cross-correlations were used to assess relationships between the motion of the individual metatarsals and the unified forefoot. Significant reductions of DMPN group sagittal plane angular excursions were detected in all individual metatarsals and the unified forefoot (p study illustrates that multiple individual metatarsals have reduced motion in people with DMPN. Differences in the magnitude and coupling between individual metatarsal motion and unified forefoot motion supports the use of a two segment forefoot modeling approach in future kinematic analyses. Further study is recommended to determine if the observed kinematic profile is related to the development and location of deformity and tissue breakdown in people with DMPN.

  19. Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

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    Jung Chan-Hee

    2012-03-01

    Full Text Available Abstract Background Cardiac autonomic neuropathy (CAN is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM. However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha, adiponectin in subjects with T2DM is limited. Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients. Methods A total of 142 T2DM patients (94 males, 48 females were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay. Results Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036. Serum leptin levels demonstrated a negative correlation with low frequency (LF in the upright position (p = 0.037. Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019. Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47] and higher homeostatic model of assessment-insulin resistance (HOMA-IR (5.47, [1.8-16.5]. The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles

  20. Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFα soluble receptor alleviates pain in rats with diabetic neuropathy.

    Science.gov (United States)

    Ortmann, Kathryn L Maier; Chattopadhyay, Munmun

    2014-10-01

    The mechanisms of diabetic painful neuropathy are complicated and comprise of peripheral and central pathophysiological phenomena. A number of proinflammatory cytokines are involved in this process. Tumor necrosis factor α (TNF-α) is considered to be one of the major contributors of neuropathic pain. In order to explore the potential role of inflammation in the peripheral nervous system of Type 1 diabetic animals with painful neuropathy, we investigated whether TNF-α is a key inflammatory mediator to the diabetic neuropathic pain and whether continuous delivery of TNFα soluble receptor from damaged axons achieved by HSV vector mediated transduction of DRG would block or alter the pain perception in animals with diabetic neuropathy. Diabetic animals exhibited changes in threshold of mechanical and thermal pain perception compared to control rats and also demonstrated increases in TNFα in the DRG, spinal cord dorsal horn, sciatic nerve and in the foot skin, 6 weeks after the onset of diabetes. Therapeutic approaches by HSV mediated expression of p55 TNF soluble receptor significantly attenuated the diabetes-induced hyperalgesia and decreased the expression of TNFα with reduction in the phosphorylation of p38MAPK in the spinal cord dorsal horn and DRG. The overall outcome of this study suggests that neuroinflammatory activation in the peripheral nervous system may be involved in the pathogenesis of painful neuropathy in Type 1 diabetes which can be alleviated by local expression of HSV vector expressing p55 TNF soluble receptor.

  1. Later stages of diabetic neuropathy affect the complexity of the neuromuscular system at the knee during low-level isometric contractions

    DEFF Research Database (Denmark)

    Suda, Eneida Y.; Sacco, Isabel C. N.; Hirata, Rogerio P.

    2017-01-01

    INTRODUCTION: The aim of this study was to evaluate the complexity of force and surface electromyography (sEMG) during knee extension and flexion at low-level isometric contractions in individuals with different degrees of diabetic peripheral neuropathy (DPN). METHODS: Ten control and 38 diabetic...

  2. Male accessory gland inlfammation prevalence in type2 diabetic patients with symptoms possibly relfecting autonomic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Rosita A Condorelli; Enzo Vicari; Aldo E Calogero; Sandro La Vignera

    2014-01-01

    Male accessory gland inlfammation or infection(MAGI) is a potentially underdiagnosed complication of type2 diabetes(DM2);speciifcally, we reported in a recent study that the frequency of MAGI was 43% among DM2patients. In previous studies, we have demonstrated that diabetic autonomic neuropathy(DAN) is associated with a peculiar ultrasound characterization of the seminal vesicles(SVs) in DM2patients. The aim of the present study was to evaluate the frequency of MAGI in two different categories of DM2patients(i.e.patients with and without symptoms that possibly relfect DAN) and the respective ultrasound characterizations. Sixty DM2patients with a mean(± s.e.m.) age of 42.0±6.0years(range: 34–47years) were classiifed according to the presence or the absence of symptoms that could possibly relfect DAN(groupA: DM2 with symptoms possibly relfecting DAN,n=28patients and groupB: DM2 without symptoms possibly relfecting DAN,n=32patients). The patients in GroupA exhibited a signiifcantly higher frequency of MAGI compared with those in groupB patients(P<0.05); moreover, the GroupA patients exhibited a signiifcantly higher frequency of ultrasound signs suggestive of vesiculitis(P<0.05). Finally, the concentrations of lymphocytes but not the concentrations of the leukocytes in the semen were signiifcantly higher(P<0.05) in groupA compared with groupB.

  3. Risk factors and pain status due to diabetic neuropathy in chronic long-term diabetic patients in a Chinese urban population

    Institute of Scientific and Technical Information of China (English)

    JI Na; ZHANG Nan; REN Zhan-jie; JIA Ke-bao; WANG Li; NI Jia-xiang; MA Jun

    2012-01-01

    Background With economic growth and urbanization there have been significant changes in the life style and diet of urban residents in large cities of China,which is experiencing a rapid increase in the prevalence of diabetes.While high prevalence of diabetes has been reported,little is known of the long-term effects of diabetes in such a large population.The aim of this study was to estimate the morbidity rate of diabetic peripheral neuropathy (DPN) in a Chinese urban diabetic population with more than 10 years' disease duration,and evaluate the relevant risk factors.The clinical manifestation of DPN and pain status was also assessed.Methods Five hundred and sixty-five diabetes patients were recruited into the study.Symptoms and examination helped diagnose neuropathy.The clinical manifestation of DPN was assessed with a visual analog pain score (VAS).Diabetic complication status was determined from medical records.Serum lipids and lipoproteins,glycosylated hemoglobin (HbA1c),and the urinary albumin excretion rate were measured.Results The morbidity rate of DPN was 46.6%.HbA1c,hyperlipidemia,and retinopathy were significantly associated with neuropathy,and these risk factors were correlated with other diabetic micro and/or macrovascular complications.The average VAS pain score of the DPN patients was 4.12±2.07.Severe and moderate pain was experienced by 11.4% and 40.5% respectively of DPN patients.About 3.7% of diabetic subjects had lower limb ulcer or amputation.Conclusions The morbidity rate of DPN for diabetic patients with >10 years duration is very high compared to the range reported for other populations in the world.The risk factors for DPN include HbA1c,hyperlipidemia,and retinopathy.In long-standing diabetic patients,DPN was not associated with diabetic duration,and half of the DPN patients experienced considerable daily suffering.

  4. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats

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    Amir Farshid

    2015-08-01

    Full Text Available Objectives: Crocin and safranal, the major constituents of saffron, exert neuroprotective effects. In the present study, we investigated the effects of crocin and safranal  (alone or in combination with insulin on peripheral neuropathy in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p. injection of 60 mg/kg of streptozotocin (STZ and confirmed by blood glucose level higher than 250 mg/dl. After confirmation of diabetes, crocin (30 mg/kg, i.p., safranal (1 mg/kg, i.p. (alone or in combination with insulin and insulin (5 IU/kg, s.c. were administered for eight weeks. Neuropathic pain was evaluated using acetone drop test. Histopathological changes of sciatic nerve were evaluated using light microscope. Blood glucose levels and sciatic nerve malondialdehyde (MDA contents were also measured. Results: STZ caused cold allodynia, edema and degenerative changes of sciatic nerve, hyperglycemia and an elevation of sciatic nerve MDA levels. Crocin, safranal and insulin improved STZ-induced behavioral, histopathological and biochemical changes. Combined treatments produced more documented improving effects. Conclusion: The results of the present study showed neuroprotective effects of crocin, safranal and insulin in a rat model of diabetic neuropathy. In addition, crocin and safranal enhanced the neuroprotective effect of insulin. The neuroprotective effects of theses chemical compounds could be associated with their anti-hyperglycemic and antioxidant properties.

  5. Heat shock protein 70 is necessary to improve mitochondrial bioenergetics and reverse diabetic sensory neuropathy following KU-32 therapy.

    Science.gov (United States)

    Ma, Jiacheng; Farmer, Kevin L; Pan, Pan; Urban, Michael J; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2014-02-01

    Impaired neuronal mitochondrial bioenergetics contributes to the pathophysiologic progression of diabetic peripheral neuropathy (DPN) and may be a focal point for disease management. We have demonstrated that modulating heat shock protein (Hsp) 90 and Hsp70 with the small-molecule drug KU-32 ameliorates psychosensory, electrophysiologic, morphologic, and bioenergetic deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of type 1 and type 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. The onset of DPN showed a tight temporal correlation with a decrease in mitochondrial bioenergetics in a genetic model of type 2 diabetes. In contrast, sensory hypoalgesia developed 10 weeks before the occurrence of significant declines in sensory neuron mitochondrial bioenergetics in the type 1 model. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70, since the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes, but not type 1 diabetes, and that modulating Hsp70 offers an effective approach toward correcting sensory neuron bioenergetic deficits and DPN in both type 1 and type 2 diabetes.

  6. Electrical stimulation and electromagnetic field use in patients with diabetic neuropathy: systematic review and meta-analysis

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    Cinara Stein

    2013-04-01

    Full Text Available BACKGROUND: Painful diabetic neuropathy (PDN is a common complication of diabetes mellitus, and pharmacological therapies are ineffective in many patients. Therefore, other treatment modalities should be considered, including electrical stimulation and electromagnetic fields. OBJECTIVES: The research objective was to evaluate the effect of treatment with electrical stimulation and electromagnetic fields on pain and sensitivity in patients with painful diabetic neuropathy compared with placebo or another intervention. METHOD: We searched the following electronic databases (from inception to April 2012: MEDLINE (accessed by PubMed, LILACS, Physiotherapy Evidence Database (PEDro, EMBASE and Cochrane CENTRAL. We included randomized trials that compared electrical stimulation or electromagnetic fields with control groups in which the objective was to assess pain and sensitivity in patients with PDN. Two reviewers independently extracted the data. A random-effects model was used for the main analysis. RESULTS: The search retrieved 1336 articles, of which 12 studies were included. Reductions in the mean pain score were significantly greater in the TENS (transcutaneous electrical nerve stimulation group than in the placebo group [-0.44 (95% CI: -0.79 to -0.09; I2: 0%]. There was no improvement in pain relief when electromagnetic fields were compared with the control group [-0.69 (95% CI: -1.86 to 0.48; I2: 63%]. CONCLUSIONS: We found that TENS improved pain relief in patients with diabetic neuropathy, while no such improvement was observed with the use of electromagnetic field treatment. Due to the methodological differences between the studies, a meta-analysis for the outcome of sensitivity could not be performed.

  7. Identification, prevalence, and treatment of painful diabetic neuropathy in patients from a rural area in South Carolina

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    Pruitt III J

    2017-04-01

    Full Text Available Jimmy Pruitt III,1 Carolina Moracho-Vilrriales,1,2 Tiffaney Threatt,3 Sarah Wagner,3 Jun Wu,1 E Alfonso Romero-Sandoval1 1Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Biochemistry and Biotechnology, University of Alcalá de Henares, Madrid, Spain; 3Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Diabetic peripheral neuropathy (DPN represents significant burdens to many patients and the public health-care system. Patients with diabetes in rural areas have higher risk of developing complications and having less access to proper treatment. We studied a rural population of patients with diabetes who attended a pharmacist-led free clinic for a diabetic education program. Our objectives were to 1 determine the prevalence of DPN and painful diabetic neuropathy (p-DN in patients with type 2 diabetes; 2 assess the proportion of patients with DPN and p-DN left undocumented upon physician referral to a pharmacist-led free clinic; and 3 determine the appropriateness of pain medication regimen. We performed a retrospective analysis of clinical records of patients from the Presbyterian College School of Pharmacy (PCSP Wellness Center located in Clinton, SC. Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical records and compared with results from foot examinations performed in the free clinic and clinical features. Medication regimens were also obtained and compared using American Academy of Neurology (AAN treatment guidelines. Within our study population (n=111, the prevalence of DPN was 62.2% (national average of 28%–45% and that of p-DN was 23.4% (national average of 11%–24%. In p-DN patients (n=26, 53.8% (n=14 had a documented diagnosis of p-DN by the referring physician, and 46.2% (n=12 were identified by the pharmacists. A total of 95% (19 of 20 of the patients treated for p

  8. Self care ability of women with diabetes who suffered from peripheral neuropathy and its related needs based on Orem’s self-care model

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    khosravan SH

    2015-11-01

    Full Text Available Background and Objective: Diabetes is associated with many complications that one of these complications is neuropathy. This disease is more common in women. In cases of self-care deficit and not meeting its related needs, the disease can lead to complications and even death. This study was done to determine the self care ability of diabetes women with peripheral neuropathy and its related need based on Orem self care model. Materials and Method: This cross - sectional study was conducted on women with diabetic peripheral neuropathy who referred to diabetes clinic in one of the hospitals in Gonabad in 2014. 120 patients were selected by convenience sampling. Patients’ neuropathy was determined by Michigan Neuropathy Screening Instrument and Toronto Clinical Neuropathy Score. Then, data were gathered through using self care needs assessment questionnaire and self care ability questionnaire based on Orem self care model. Data analysis was done through using descriptive statistical test and chi-square test with in SPSS 17. Results: The self care ability of 71.7 percent of patients was weak (33.72 ± 8.48 and according to needs assessment and in domains of knowledge, attitude and performance, 10.8, 0.8 and 52.5 percent of subjects were weak respectively. Conclusion: According to the findings, the self care ability of diabetic women with peripheral neuropathy was weak. The domain of performance was weaker than attitude and knowledge domains concerning the self care ability. Therefore, it is recommended to design and implement of necessary measures for improving the patients’ self care ability based on their needs.

  9. Evaluation of atrophy of foot muscles in diabetic neuropathy -- a comparative study of nerve conduction studies and ultrasonography

    DEFF Research Database (Denmark)

    Severinsen, Kaare; Andersen, Henning

    2007-01-01

    OBJECTIVE: To evaluate the relation between the findings at nerve conduction studies and the size of small foot muscles determined by ultrasonography. METHODS: In 26 diabetic patients the size of the extensor digitorum brevis muscle (EDB) and of the muscles between the first and second metatarsal...... related to the size of the small foot muscles as determined by ultrasonography. SIGNIFICANCE: In diabetic patients motor nerve conduction studies can reliably determine the size of small foot muscles. Udgivelsesdato: 2007-Oct....... RESULTS: Seventeen patients fulfilled the criteria for diabetic neuropathy. The cross-sectional area of the EDB muscle and the thickness of the MIL muscle were 116 +/- 65 mm2 and 29.6 +/- 8.2 mm, respectively. Close relations were established between muscle size and the amplitude of the CMAP...

  10. Decreased Endomorphin-2 and μ-Opioid Receptor in the Spinal Cord Are Associated with Painful Diabetic Neuropathy

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    Kou, Zhen-Zhen; Wan, Fa-Ping; Bai, Yang; Li, Chun-Yu; Hu, Jia-Chen; Zhang, Guo-Tao; Zhang, Ting; Chen, Tao; Wang, Ya-Yun; Li, Hui; Li, Yun-Qing

    2016-01-01

    Painful diabetic neuropathy (PDN) is one of the most common complications in the early stage of diabetes mellitus (DM). Endomorphin-2 (EM2) selectively activates the μ-opioid receptor (MOR) and subsequently induces antinociceptive effects in the spinal dorsal horn. However, the effects of EM2-MOR in PDN have not yet been clarified in the spinal dorsal horn. Therefore, we aimed to explore the role of EM2-MOR in the pathogenesis of PDN. The main findings were the following: (1) streptozotocin (STZ)-induced diabetic rats exhibited hyperglycemia, body weight loss and mechanical allodynia; (2) in the spinal dorsal horn, the expression levels of EM2 and MOR decreased in diabetic rats; (3) EM2 protein concentrations decreased in the brain, lumbar spinal cord and cerebrospinal fluid (CSF) in diabetic rats but were unchanged in the plasma; (4) the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) was significantly higher in diabetic rats than in control rats; and (5) intrathecal injection of EM2 for 14 days in the early stage of PDN partially alleviated mechanical allodynia and reduced MOR expression in diabetic rats. Our results demonstrate that the EM2-MOR signal may be involved in the early stage of PDN. PMID:27656127

  11. Decreased endomorphin-2 and opioidreceptor in the spinal cord are associated with painful diabetic neuropathy

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    Zhen-Zhen Kou

    2016-09-01

    Full Text Available Painful diabetic neuropathy (PDN is one of the most common complications in the early stage of diabetes mellitus (DM. Endomorphin-2 (EM2 selectively activates the opioid receptor (MOR and subsequently induces antinociceptive effects in the spinal dorsal horn. However, the effects of EM2-MOR in PDN have not yet been clarified in the spinal dorsal horn. Therefore, we aimed to explore the role of EM2-MOR in the pathogenesis of PDN. The main findings were the following: (1 streptozotocin (STZ-induced diabetic rats exhibited hyperglycemia, body weight loss and mechanical allodynia; (2 in the spinal dorsal horn, the expression levels of EM2 and MOR decreased in diabetic rats; (3 EM2 protein concentrations decreased in the brain, lumbar spinal cord and CSF in diabetic rats but were unchanged in the plasma; (4 the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs was significantly higher in diabetic rats than in control rats; and (5 intrathecal injection of EM2 for 14 days in the early stage of PDN partially alleviated mechanical allodynia and reduced MOR expression in diabetic rats. Our results demonstrate that the EM2-MOR signal may be involved in the early stage of PDN.

  12. Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy.

    Science.gov (United States)

    Pagkalos, M; Koutlianos, N; Kouidi, E; Pagkalos, E; Mandroukas, K; Deligiannis, A

    2008-01-01

    Cardiac autonomic neuropathy (CAN) as a result of diabetic autonomic neuropathy is positively related to a poor prognosis in diabetic patients. The measurement of heart rate variability (HRV) is a remarkable index of cardiac autonomic dysfunction. The aim of this study was to examine the effects of long-term exercise training on HRV in type 2 diabetic patients with definite CAN. Seventeen type 2 diabetic patients with definite CAN (group A: 56.2 years (SD 5.8)) and 15 without CAN (group B: 55.8 years (SD 5.6)) participated in the study. All patients followed an aerobic exercise training programme three times a week for 6 months; the intensity of the session was 70% to 85% of heart rate reserve. At the beginning and end of the study all subjects underwent graded maximal exercise testing with spiroergometry for the evaluation of their aerobic capacity (VO(2)peak). Moreover, time and frequency domain indices of HRV were obtained from 24 h ambulatory continuous ECG Holter recordings. At baseline, all measurements of HRV indices were significantly reduced in group A compared with group B (pexercise training programme, the SD of all normal-to-normal RR intervals in the entire recording (SDNN) was increased by 18.8% (pexercise training programme, SDNN, rMSSd and low frequency power (LF) were significantly lower (24.3% (pexercise training programme had significant effects on blood lipid and glucose levels and glycosylated haemoglobin (HbA(1c)) in both groups. The results indicate that 6-month aerobic exercise training improves the cardiac autonomic nervous system function in type 2 diabetic patients. However, more favourable effects are found in type 2 diabetic patients with definite CAN.

  13. Incidence of repeat amputation after partial first ray amputation associated with diabetes mellitus and peripheral neuropathy: an 11-year review.

    Science.gov (United States)

    Borkosky, Sara L; Roukis, Thomas S

    2013-01-01

    The reliability and durability of partial first ray amputation in patients with diabetes and peripheral neuropathy has recently been questioned. In an effort to determine the repeat amputation rate after a partial first ray amputation associated with diabetes mellitus and peripheral neuropathy at our institution, we performed an 11-year retrospective review. A total of 59 patients (40 males and 19 females), with a mean age of 63 (range 39 to 97) years, were included. The mean follow-up was 33.8 (range 1 to 123) months, with initial incision healing occurring in all 59 patients. Despite the initial healing, 69% developed a mean of 3.1 subsequent foot ulcerations at a mean of 10.5 months, 36% required ancillary surgical procedures, and more than 90% of patients were prescribed multiple courses of antibiotics at a mean of 26.6 clinic visits during the follow-up period. A total of 25 patients (42.4%) underwent more proximal repeat amputation at a mean of 25 (range 1 to 97) months after the initial partial first ray amputation. The results of our retrospective review revealed that nearly 1 of every 2 patients with diabetes and peripheral neuropathy who undergo a partial first ray amputation will progress to a more proximal repeat amputation, despite initial healing. These data question the reliability and durability of this level of amputation as a primary procedure in this patient population. A more proximal level amputation, such as a balanced transmetatarsal, might provide a better functional and reliable residual weightbearing foot and should be considered at the initial presentation. This is especially true given that nearly one half of the patients died during the follow-up period. However, this remains a matter for conjecture because of the limited data available; therefore, additional prospective investigations are warranted.

  14. Protein Mediated Oxidative Stress in Patients with Diabetes and its Associated Neuropathy: Correlation with Protein Carbonylation and Disease Activity Markers

    Science.gov (United States)

    Almogbel, Ebtehal

    2017-01-01

    Introduction Free radicals have been implicated as Diabetes Mellitus (DM) contributors in type 2 DM and its associated Diabetes Mellitus Neuropathy (DMN). However, the potential for protein mediated oxidative stress to contribute disease pathogenesis remains largely unexplored. Aim To investigate the status and contribution of protein mediated oxidative stress in patients with DM or DMN and to explore whether oxidative protein modification has a role in DM progression to DM associated neuropathy. Materials and Methods Sera from 42 DM and 37 DMN patients with varying levels of disease activities biomarkers (HbA1C, patients’ age or disease duration) and 21 age- and sex-matched healthy controls were evaluated for serum levels of protein mediated oxidative stress. Results Serum analysis showed significantly higher levels of protein carbonyl contents in both DM and DMN patients compared with healthy controls. Importantly, not only was there an increased number of subjects positive for protein carbonylation, but also the levels of protein carbonyl contents were significantly higher among DM and DMN patients, whose HbA1C were ≥8.8 as compared with patients with lower HbA1C (HbA1Cdiabetes to diabetes neuropathy. Conclusion These findings support an association between protein oxidation and DM or DMN progression. The stronger response observed in patients with higher HbA1C or patients’ ages or disease durations suggests, that protein mediated oxidative stress may be useful in evaluating the progression of DM and its associated DMN and in elucidating the mechanisms of these disorders pathogenesis.

  15. Effect of mouse nerve growth factor combined with mecobalamine on treatment of diabetic peripheral neuropathy

    Institute of Scientific and Technical Information of China (English)

    De-Rong Hu

    2016-01-01

    Objective:To observe the clinical effect of mouse nerve growth fact (NGF) combined with mecobalamine on treatment of diabetic peripheral n-europathy (DPN).Methods:A total of 84 cases of patients with DPN treated in ourhospital between April 2012 and June 2015 were selected, and divided into study group and control group randomly (n=42); Control group was only given mecobalamine treatment, while study group was given mouse nerve growth factor combined with mecobalamine treatment for 4 weeks. TThe motor nerve conduction velocity median nerve (MNCV), sensory nerve conduction velocity (SNCV), serum high sensitivity c-reactive protein (hs-CRP) and Toronto clinical scoring system (TCSS) changes of median nerve and nervus peroneus communis before and after treatment were compared. Results:There were no significant differences in MNCV, SNCV of mediannerve and nervus peroneus communis before treatment. MNCV and SNCV of both groups after treatment were significantly increased. MNCV, SNCV of mediannerve and nervus peroneus communis in study group was significantly higher than that in control group. hs-CRP and TCSS scoring of both groups before treatment showed no statistic significant difference. hs-CRP scoring of both groups after treatment showed no significant difference. TCSS scoring was significantly lower than that in control group. Adverse reaction total occurrence rate after given drug in study group was 16.67% (7/42), compared with 7.14% (3/42) in control group, difference was significant.Conclusions:Mouse NGF combined with mecobalamine could achieve good curative effect. It is of higher safety in the treatment of patients with DPN, and deserves popularization and application.

  16. Manual acupuncture for treatment of diabetic peripheral neuropathy: a systematic review of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available OBJECTIVE: Manual acupuncture has commonly been used in China, either alone or in combination with conventional medicine, to treat diabetic peripheral neuropathy (DPN. The objective of this study was to perform a systematic review to evaluate the potential benefits and harms of manual acupuncture for DPN to justify its clinical use. METHODS: We searched for published and unpublished randomized controlled trials of manual acupuncture for DPN till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR and mean difference (MD with a 95% confidence interval (CI. RESULTS: A total of 25 trials involving 1649 participants were included. The methodological quality of included trials was generally poor. Meta-analysis showed that manual acupuncture had better effect on global symptom improvement compared with mecobalamin (RR 1.31, 95%CI 1.21 to 1.42, vitamin B1 and B12 (RR 1.55, 95%CI 1.33 to 1.80, and no treatment (RR 1.56, 95%CI 1.31 to 1.85, and that the combination of manual acupuncture and mecobalamin had better effect compared with mecobalamin alone on global symptom improvement (RR 1.56, 95%CI 1.28 to 1.90. Adverse events were not reported in any trials. The asymmetric funnel plot suggested publication bias. CONCLUSIONS: Despite the number of trials of manual acupuncture for DPN and their uniformly positive results, no clinically relevant conclusions can be drawn from this review due to the trials' high risks of bias and the possibility of publication bias. Clearly defined and internationally acknowledged outcome measures are required for future study. There remains an urgent need for training Chinese researchers in conducting unbiased trials as well as prospectively registering all initiated Chinese trials to avoid publication bias.

  17. Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus

    DEFF Research Database (Denmark)

    Lindberger, M; Schröder, H D; Schultzberg, M

    1989-01-01

    Standardised skin biopsies followed by immunohistochemical examination for the presence of terminal nerve fibres reacting for neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated. Healthy subjects regularly displayed free nerve endings of both fibre types...... in the dermis layers. Five type I diabetes patients without clinical or neurophysiological evidence of polyneuropathy also had reduced density of both fibre types, being significant for CGRP fibres when compared with controls. Skin biopsy with immunohistochemical staining for neuropeptides may represent...... a sensitive tool in evaluation of patients with peripheral neuropathies....

  18. Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicenter, double-blind, placebo-controlled trial in patients with diabetes mellitus.

    Science.gov (United States)

    Backonja, M M

    1999-01-01

    Pain is the most disturbing symptom of diabetic neuropathy. Traditionally this type of pain was treated with tricyclic antidepressants which frequently have many side effects. In the study reported here, gabapentin was administered in escalating doses up to 3600 mg per day to eligible patients with moderate to severe diabetic neuropathy pain in a double blind placebo controlled fashion. Gabapentin provided superior and significant pain relief over placebo. In addition, patients taking gabapentin had improvement of sleep scores and a number of items on mood and quality of life questionnaires. Gabapentin was tolerated well with mild and tolerable side effects.

  19. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes.

    Science.gov (United States)

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S

    2011-11-01

    High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.

  20. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Anders A.F. Sima

    2014-01-01

    Full Text Available Objective — we evaluated frozen databases from two 52‑week randomized placebocontrolled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (alc: 500 and 1,000 mg / day t. i. d.Research design and methods — intention-to-treat patients amounted to 1,257 or 93 % of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.Results — data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg alc.Conclusions — these studies demonstrate that alc treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.

  1. Effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    Ya-Li Hao

    2016-01-01

    Objective:To analyze the effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy.Methods: A total of 55 patients (82 eyes) with diabetic optic neuropathy treated in our hospital between December 2013 and December 2015 were selected, and according to different therapeutic methods, they were divided into observation group (n=38) (49 eyes) who received Maixuekang therapy and control group (n=17) (33 eyes) who received compound vitamin therapy. Differences in optic nerve function, blood coagulation function and cytokine content were compared between two groups after 3 months of treatment.Results:After 3 months of treatment, optic nerve function indexes MS, RNFL thickness and AP100 levels of observation group were higher than those of control group while MD and LP100 levels were lower than those of control group; blood coagulation indexes WBV, PV and FBG levels were lower than those of control group while TT, PT and APTT levels were higher than those of control group; thrombelastogram parameters R value and K value levels were higher than those of control group while α angle, MA and CI levels were lower than those of control group; oxidative stress indexes ROS, MDA and CAT content in serum were lower than those of control group while SOD content was higher than that of control group.Conclusions:Maixuekang capsule can significantly optimize the optic nerve function in patients with DON, which is specifically directly related to its anticoagulation and anti-oxidative stress effect.

  2. The Comparison between Effects of 12 weeks Combined Training and Vitamin D Supplement on Improvement of Sensory-motor Neuropathy in type 2 Diabetic Women

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    Maryam Nadi

    2017-01-01

    Full Text Available Background: Peripheral neuropathy is a common complaint of diabetes. This study aimed to determine the effects of 12 weeks combined training with Vitamin D supplement on improvement of sensory-motor neuropathy in women with diabetic neuropathy. Materials and Methods: This clinical trial study conducted on 90 patients were selected and randomly divided into two groups. Finally, 81 adult females with diabetes type II (20–55 years old were interred in this study. The control group had no training, but received Vitamin D. The experimental group received Vitamin D and 12 weeks training program (3 days a week, 60 min/session including aerobic exercises, strength, and flexibility. Aerobic exercise intensity was set at 60–70% maximum heart rate and resistance training intensity was determined by 10 R.M. Michigan neuropathy questionnaire, reflex hammer and tuning fork 128 Hz used to screening tense of neuropathy (Michigan Neuropathy Screening Instrument that were used for pretest and posttest. Results: Following 3 months combined training and supplementation with Vitamin D, had observed a significant reduction in numbness (P = 0.001, pain (0.002, tingling (P = 0.001, and weakness (P = 0.002 in the lower limb and also increases in sense of touch intervention (P = 0.005, detects the position of the fingers (P = 0.001 and vibration perception (P = 0.001 in tissues. Knee reflexes (P = 0.77 and ankles reflexes (P = 0.47 did not significantly change after interventions. Conclusion: It seems that taking part in combined training and supplementation with Vitamin D can improve the symptoms of sensory-motor neuropathy.

  3. Effects of poly (ADP-ribose) polymerase inhibitor on early peripheral neuropathy in streptozotocin-diabetic rat

    Institute of Scientific and Technical Information of China (English)

    Wei Guo; Chenghong Zheng; Jie Xu

    2007-01-01

    Objective: To explore the effects and mechanisms of poly (ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide on nerve lesions in streptozotocin-diabetic rats. Methods: Experimental rats were divided into normal control group(NC group), diabetic control group (DC group)and diabetic group treated with 3-aminobenzamide (DT group ) .Nerve conduction velocity (NCV),serum superoxide dismutase (SOD) activity and serum malondialdehyde (MDA) concentration,phosphocreatine (Pcr),creatine (Cr) concentration in sciatic nerves were evaluated after 4 weeks. Results: SOD, Pcr activity, and NCV were higher (P < 0.05)and MDA concentration were significantly lower in DT group, compared with DC group (P < 0.01). Meanwhile, ATP and Cr in sciatic nerves were similar in DT group, compare d with DC group (P > 0.05). Conclusion: 3-aminobenzamide could alleviate the established functional and metabolic abnormalities of early DPN in the streptozotocin-induced diabetic rat models,which provided a novel approach for prevention and treatment of diabetic neuropathy.

  4. Partial Replacement with Menhaden Oil Improves Peripheral Neuropathy in High-Fat-Fed Low-Dose Streptozotocin Type 2 Diabetic Rat

    Directory of Open Access Journals (Sweden)

    Lawrence J. Coppey

    2012-01-01

    Full Text Available Aims. To determine the effect of partial replacement of a high-fat diet with menhaden oil on diabetic neuropathy in an animal model of type 2 diabetes. Materials and Methods. High-fat/low-dose streptozotocin diabetic rats were used to examine the influence of replacing 50% of the source of the high-fat diet (lard with menhaden oil, a natural source of n-3 fatty acids, on diabetic neuropathy. Endpoints included analyses of glucose tolerance, fatty liver disease, serum and liver fatty acid composition, serum lipid and adiponectin levels, motor and sensory nerve conduction velocity, thermal sensitivity and innervation of the hindpaw. Results. Diabetic rats were insulin resistant and menhaden oil did not improve whole animal glucose utilization. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels but serum levels of adiponectin were significantly increased and hepatic steatosis was significantly improved. Diabetic rats were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities and intraepidermal nerve fiber profiles were decreased in the hindpaw and these endpoints were significantly improved with menhaden oil. Conclusions. We found that enrichment of a high-fat diet with menhaden oil improved a number of endpoints associated with diabetic neuropathy.

  5. Peripheral neuropathies.

    Science.gov (United States)

    Hanewinckel, R; Ikram, M A; Van Doorn, P A

    2016-01-01

    Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies. © 2016 Elsevier B.V. All rights reserved.

  6. 神经生长因子与糖尿病神经病变的研究进展%Research Progress in NGF and Diabetic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    贾彩霞; 王元松

    2012-01-01

    Diabetic neuropathy is one of the common complications in diabetes. Nerve growth factor ( NGF )is important in the occuruence and development of diabetic neuropathy. NGF is a signal molecule the activity is regulated by tyrosine kinase receptor and p75 neurotrophin receptor. NGF can regulate central and periheral nerve growth and survival; and nerve growth factor can selectively nuture small nerve fibres sensory neurons and sympathetic neurons. In the anmial experiments and clinical studies, lots of evidence shows that NGF is closely related with diabetic neuropathy. It is useful to research the relationship between NGF and diabetic neuropathy for new perspectives for prevention and treatment of diabetic neuropathy.%糖尿病神经病变是糖尿病常见并发症之一.神经生长因子(NGF)在糖尿病神经病变的发生和发展中发挥重要作用.NGF是一种信号分子,其生物活性受酪氨酸激酶受体A和p75神经营养因子受体的调节.NGF能调节中枢神经和外周神经的生存和生长,并且NGF能选择性地营养小神经纤维感觉神经元和交感神经元.在动物模型和临床研究中,均有证据表明NGF与糖尿病神经病变关系密切.研究NGF与糖尿病神经病变的关系将有助于为糖尿病神经病变的防治提供新的研究思路.

  7. A review on treating diabetic peripheral neuropathy in TCM%糖尿病周围神经病变的中医药治疗概况

    Institute of Scientific and Technical Information of China (English)

    高言歌; 唐爱华

    2014-01-01

    Diabetic peripheral neuropathy (diabetic peripheral neuropathy, DPN) is one of the chronic complications of diabetes, TCM treatment showed a unique advantage in the clinical treatment of the disease; based on the recent paper, TCM disease-related literature review and their treatment methods commonly used in medicine were summarized.%糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)是糖尿病慢性并发症之一,中医药以其多样化的治疗方法、辨证施治的治疗理念在该病的临床治疗中发挥独特优势,本文就近年来中医药治疗该病相关文献整理,对其常用中医药治疗方法进行综述。

  8. Treating Diabetic Peripheral Neuropathy from Dryness Pathogen%从燥论治糖尿病周围神经病变

    Institute of Scientific and Technical Information of China (English)

    姜南; 王强

    2014-01-01

    糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)是糖尿病的慢性并发症之一,属于中医的“痹证”、“痛证”、“痿证”等范围.分析“燥”在DPN发病中的作用.

  9. Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2001-01-01

    , Redmond, WA), and UAER was determined through three overnight urine samples. The subjects with parental type 2 diabetes had significantly lower heart rate variation in all three bedside tests (P ...The aim of this study was to examine the impact of parental type 2 diabetes on the autonomic nervous system and to determine whether autonomic neuropathy is present and associated with changes in 24-h ambulatory blood pressure (AMBP) and urinary albumin excretion rate (UAER) in nondiabetic subjects...

  10. An evaluation of the protective role of Ficus racemosa Linn. in streptozotocin-induced diabetic neuropathy with neurodegeneration

    Directory of Open Access Journals (Sweden)

    Nilay D Solanki

    2015-01-01

    Full Text Available Objective: Ficus racemosa (FR is one of the herbs mentioned in the scriptures of the Ayurveda as Udumbara with high medicinal value. The objective of this study was to estimate the protective effect of FR against streptozotocin (STZ induced diabetic neuropathy with neurodegeneration (DNN. Materials and Methods: Diabetes was induced in Wistar rats with STZ and were divided into six groups namely diabetic vehicle control, FR (four and glibenclamide (one treated rats; while one group was of normal control rats. After the 4th week of diabetes, induction treatment was started for further 28 days (5th to 8th week with FR aqueous extract (250 mg/kg and 500 mg/kg and ethanolic extract (200 mg/kg and 400 mg/kg. Investigation of DNN was carried out through biochemical and behavioral parameter assessment in rats. Results: Study showed a significant fall in glycosylated hemoglobin (HbA1c and blood glucose level by the treatment of FR in diabetic rats. Antioxidant potential of FR showed a great rise in superoxide dismutase, catalase content and reduction observed in serum nitrite level; while significant fall in lipid peroxidation level and of C-reactive protein was observed in FR treated diabetic rats. Further FR treated diabetic rats also showed marked improvement in tail flick latency, pain threshold, the rise in locomotion and fall latency period. Conclusion: Treatment with FR shows protection in the multiple pathways of DNN by improving blood glucose, HbA1c, biochemical, and behavioral parameters, which suggest the protective role of FR in the reversal of DNN.

  11. Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy.

    Science.gov (United States)

    Bierhaus, Angelika; Fleming, Thomas; Stoyanov, Stoyan; Leffler, Andreas; Babes, Alexandru; Neacsu, Cristian; Sauer, Susanne K; Eberhardt, Mirjam; Schnölzer, Martina; Lasitschka, Felix; Lasischka, Felix; Neuhuber, Winfried L; Kichko, Tatjana I; Konrade, Ilze; Elvert, Ralf; Mier, Walter; Pirags, Valdis; Lukic, Ivan K; Morcos, Michael; Dehmer, Thomas; Rabbani, Naila; Thornalley, Paul J; Edelstein, Diane; Nau, Carla; Forbes, Josephine; Humpert, Per M; Schwaninger, Markus; Ziegler, Dan; Stern, David M; Cooper, Mark E; Haberkorn, Uwe; Brownlee, Michael; Reeh, Peter W; Nawroth, Peter P

    2012-06-01

    This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na(v)1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy.

  12. TIME AND FREQUENCY DOMAIN ANALYSIS OF HEART RATE VARIABILITY SIGNAL IN PROGNOSIS OF TYPE 2 DIABETIC AUTONOMIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    SARIKA TALE,

    2011-04-01

    Full Text Available Heart disease occurs eventually in majority of patients with diabetes mellitus and to be the outstanding factor in over all diabetes morbidity and mortality rates. Thus the timely detection of diabetic autonomic neuropathy and the use of effective means to improve autonomic nervous system function become of almost significance. In this work Electrocardiogram (ECG data of 20 Diabetes Mellitus (DM and 20 normal control volunteers were recorded and autonomic nervous system activities are quantified by means of frequency and time domainanalysis. Time domain measure ,Standard deviation of successive NN intervals (SDNN,NN intervals differing more than 50 msec.( NN50 count,Percentage value of NN50 count( pNN50 count, HRV triangular index, show a lower variation in the DM patient group compared to normal subjects and p value <0.01. The frequency domain measures indicate significant differences in very low frequency (VLF, low frequency (LF power and high frequency (HF power. Value generated from the ratio of low frequency to high frequency, (LF/HF ispretty high, with not much significance between both groups.

  13. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Linlin Yang

    2016-09-01

    Full Text Available Diabetes mellitus (DM is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN is complex and incompletely understood. Voltage-gated sodium channels (VGSCs link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.

  14. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

    Science.gov (United States)

    Yang, Linlin; Li, Quanmin; Liu, Xinming; Liu, Shiguang

    2016-01-01

    Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy. PMID:27608006

  15. Study of Vitamin B 12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus

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    Rudra Prasad Roy

    2016-01-01

    Full Text Available Background: Long-term therapy with metformin was shown to decrease the Vitamin B 12 level and manifested as peripheral neuropathy. Aim: The aim of this study is to define the prevalence of Vitamin B 12 deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years and the relationship among metformin exposure and levels of cobalamin (Cbl, folic acid, and homocysteine (Hcy with severity of peripheral neuropathy. Methodology: This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34 between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A (n = 35 with those without metformin (Group B (n = 35 and patients taking metformin with other oral hypoglycemic agent (Group C (n = 20. Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid, and with electrophysiological measures (nerve conduction studies of all four limbs. Comorbidities contributing to neuropathy were excluded from the study. Results: Group A patients (54.28% were prone to develop peripheral neuropathy comparing Group B (28.57% and Group C (35%. There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml than in Group B (mean 627.543 pg/ml and Group C (mean 419.920 pg/ml. There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml than in Group B (16.81 ng/ml and Group C (22.50 ng/ml. There was significantly high level of Hcy in Group A (mean 17.35 µmol/L and Group C (mean 16.99 µmol/L than in Group B (mean 13.22 µmol/L. Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups (F [2, 87] = 28.1, P = 0.000, (F [2, 87] = 7.43, P = 0.001, (F [2, 87] = 9.76, P

  16. The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

    Science.gov (United States)

    Babizhayev, Mark A; Strokov, Igor A; Nosikov, Valery V; Savel'yeva, Ekaterina L; Sitnikov, Vladimir F; Yegorov, Yegor E; Lankin, Vadim Z

    2015-04-01

    Diabetic neuropathy (DN) represents the main cause of morbidity and mortality among diabetic patients. Clinical data support the conclusion that the severity of DN is related to the frequency and duration of hyperglycemic periods. The presented experimental and clinical evidences propose that changes in cellular function resulting in oxidative stress act as a leading factor in the development and progression of DN. Hyperglycemia- and dyslipidemia-driven oxidative stress is a major contributor, enhanced by advanced glycation end product (AGE) formation and polyol pathway activation. There are several polymorphous pathways that lead to oxidative stress in the peripheral nervous system in chronic hyperglycemia. This article demonstrates the origin of oxidative stress derived from glycation reactions and genetic variations within the antioxidant genes which could be implicated in the pathogenesis of DN. In the diabetic state, unchecked superoxide accumulation and resultant increases in polyol pathway activity, AGEs accumulation, protein kinase C activity, and hexosamine flux trigger a feed-forward system of progressive cellular dysfunction. In nerve, this confluence of metabolic and vascular disturbances leads to impaired neural function and loss of neurotrophic support, and over the long term, can mediate apoptosis of neurons and Schwann cells, the glial cells of the peripheral nervous system. In this article, we consider AGE-mediated reactive oxygen species (ROS) generation as a pathogenesis factor in the development of DN. It is likely that oxidative modification of proteins and other biomolecules might be the consequence of local generation of superoxide on the interaction of the residues of L-lysine (and probably other amino acids) with α-ketoaldehydes. This phenomenon of non-enzymatic superoxide generation might be an element of autocatalytic intensification of pathophysiological action of carbonyl stress. Glyoxal and methylglyoxal formed during metabolic

  17. Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes

    Science.gov (United States)

    Thipkaew, Chonlathip

    2017-01-01

    In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion. PMID:28251151

  18. Studies on the Pathogenesis of Diabetic Peripheral Neuropathy%糖尿病周围神经病变发病机制研究进展

    Institute of Scientific and Technical Information of China (English)

    赵珩; 余江毅

    2013-01-01

    糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)是糖尿病最常见的慢性并发症之一.目前已发现糖代谢异常、脂代谢异常、微血管病变等可以导致DPN的发生.同时,Schwann细胞学说、免疫因素、神经生长因子及维生素缺乏等也被认为是DPN的发病机制.%Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes.Several pathological factors have been found to be associated with hyperglycemia,dyslipidemia and dysfunction of vascular especially microvascularr.Schwann cell theory,lacking of vitamin,immune factors and nerve growth factors(NGF) may also considered to be the pathological factors.

  19. TCM and western medicine research progress of diabetic peripheral neuropathy%糖尿病周围神经病变的中西医研究进展

    Institute of Scientific and Technical Information of China (English)

    李鸣镝; 倪青; 林兰

    2010-01-01

    糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)是糖尿病常见的慢性并发症之一.本文综述了糖尿病周围神经病变的病因病机、中医药辨证论治以及现代医学方面的研究进展.%Diabetic peripheral neuropathy (DPN) is a common complication of diabetic mellitus. The treatment is so difficult that doctors have not found reliable methods to cure this disease. The research progress both in TCM and western medicine of this disease were reviewed in terms of aspects of etiology, pathogenesis and differential treatments.

  20. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  1. The role of autonomic neuropathy as a risk factor of Helicobacter pylori infection in dyspeptic patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Gentile, S; Turco, S; Oliviero, B; Torella, R

    1998-10-01

    A high prevalence of upper gastrointestinal symptoms is described in diabetic patients and, at least in part, this has been attributed to abnormal emptying of the stomach. In an unselected small series of dyspeptic patients with Type 2 diabetes mellitus (DM2), we previously described a higher prevalence of Helicobacter pylori (Hp) infection associated with autonomic neuropathy (AN) than in non-diabetic subjects. To evaluate the prevalence of Hp and its relationship with AN, we studied 164 DM2 patients, matched for sex, age ( +/- 5 years) and body weight ( +/- kg) to 164 non-diabetic subjects, all affected with dyspepsia of unknown origin. Results document that the prevalence of peptic ulcer is similar in both groups of patients (20.1 vs 29.3% P = n.s.); chronic gastritis was 50% in the control group and 35.4% in the DN2 group (P diabetics (44.5 vs 20.7%, P diabetic subjects. In addition, in diabetic patients the frequency of non-ulcer, non-gastritis dyspepsia is two times higher than in non-diabetics and is strictly associated with autonomic neuropathy, acting as a favoring factor for occurrence and recurrence of gastrointestinal disease.

  2. Sixty-one Patients with Diabetic Peripheral Neuropathy Treated by Tongluo Yangyin Recipe(通络养阴方)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To observe the therapeutic effect of Tongluo Yangyin Recipe (通络养阴方, TLYYR) in patients with diabetic peripheral neuropathy (DPN). Methods: Ninety-nine patients with diabetes mellitus type 2 were assigned, according to the order of their visit, to two groups: 61 in the treated group and 38 in the control group. They were given the same information about diabetes mellitus and treated with the same therapy: strict diet control and Western drugs for hypoglycemia. In addition, the treated group received one dose (200 mL) of TLYYR in water decoction every day in two portions, while the control group had vitamin B1 100 mg and vitamin B12 250 μg administered daily via intramuscular injection. The course for all patients was 28 days. Results: The treated group experienced a therapeutic effect superior to that of the control group, with the difference between the total effective rates and the markedly effective rates (P<0.05, P<0.01). The blood levels of total cholesterol (TC) and triglyceride (TG) fell, the hemorrheological manner improved, the transmission velocity of the median nerve and common peroneal nerve significantly increased in the treated group after treatment (P<0.05),although the treatment showed no significant influence on blood glucose level (P>0.05). Conclusion:TLYYR could promote blood microcirculation, improve nutritional metabolism of peripheral nerve, and thus accelerating DPN repair.

  3. A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Slangen, Rachel; Faber, Catharina G; Schaper, Nicolaas C; Joosten, Elbert A; van Dongen, Robert T; Kessels, Alfons G; van Kleef, Maarten; Dirksen, Carmen D

    2017-04-01

    The objective was to perform an economic evaluation comparing spinal cord stimulation (SCS) in combination with best medical treatment (BMT) with BMT in painful diabetic peripheral neuropathy patients. Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. Incremental cost-effectiveness ratios were based on: 1) societal costs and quality-adjusted life years (QALYs), and 2) direct health care costs and the number of successfully treated patients, respectively, both with a time horizon of 12 months. Bootstrap and secondary analyses were performed to address uncertainty. Total societal cost amounted to €26,539.18 versus €5,313.45 per patient in the SCS and BMT group, respectively. QALYs were .58 versus .36 and the number of successfully treated patients was 55% versus 7% for the SCS and BMT group, respectively. This resulted in incremental cost-effectiveness ratios of €94,159.56 per QALY and €34,518.85 per successfully treated patient, respectively. Bootstrap analyses showed that the probability of SCS being cost-effective ranges from 0 to 46% with willingness to pay threshold values ranging between €20,000 and €80,000 for a QALY. Secondary analyses showed that cost-effectiveness of SCS became more favorable after correcting for baseline cost imbalance between the 2 groups, extending the depreciation period of SCS material to 4 years, and extrapolation of the data up to 4 years. Although SCS was considerably more effective compared with BMT, the substantial initial investment that is required resulted in SCS not being cost-effective in the short term. Cost-effectiveness results were sensitive to baseline cost imbalances between the groups and the depreciation period of the SCS material.

  4. Peripheral Neuropathy

    Science.gov (United States)

    ... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. × Definition Peripheral neuropathy ... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. View Full Definition ...

  5. Metabolic neuropathies

    Science.gov (United States)

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  6. Mitochondrial dynamics in peripheral neuropathies.

    Science.gov (United States)

    Sajic, Marija

    2014-08-01

    Mitochondrial dynamics describes the continuous change in the position, size, and shape of mitochondria within cells. The morphological and functional complexity of neurons, the remarkable length of their processes, and the rapid changes in metabolic requirements arising from their intrinsic excitability render these cells particularly dependent on effective mitochondrial function and positioning. The rules that govern these changes and their functional significance are not fully understood, yet the dysfunction of mitochondrial dynamics has been implicated as a pathogenetic factor in a number of diseases, including disorders of the central and peripheral nervous systems. In recent years, a number of mutations of genes encoding proteins that play important roles in mitochondrial dynamics and function have been discovered in patients with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. These findings have directly linked mitochondrial pathology to the pathology of peripheral nerve and have identified certain aspects of mitochondrial dynamics as potential early events in the pathogenesis of CMT. In addition, mitochondrial dysfunction has now been implicated in the pathogenesis of noninherited neuropathies, including diabetic and inflammatory neuropathies. The role of mitochondria in peripheral nerve diseases has been mostly examined in vitro, and less so in animal models. This review examines available evidence for the role of mitochondrial dynamics in the pathogenesis of peripheral neuropathies, their relevance in human diseases, and future challenges for research in this field.

  7. Predictors of barefoot plantar pressure during walking in patients with diabetes, peripheral neuropathy and a history of ulceration.

    Directory of Open Access Journals (Sweden)

    Ruth Barn

    Full Text Available Elevated dynamic plantar foot pressures significantly increase the risk of foot ulceration in diabetes mellitus. The aim was to determine which factors predict plantar pressures in a population of diabetic patients who are at high-risk of foot ulceration.Patients with diabetes, peripheral neuropathy and a history of ulceration were eligible for inclusion in this cross sectional study. Demographic data, foot structure and function, and disease-related factors were recorded and used as potential predictor variables in the analyses. Barefoot peak pressures during walking were calculated for the heel, midfoot, forefoot, lesser toes, and hallux regions. Potential predictors were investigated using multivariate linear regression analyses. 167 participants with mean age of 63 years contributed 329 feet to the analyses.The regression models were able to predict between 6% (heel and 41% (midfoot of the variation in peak plantar pressures. The largest contributing factor in the heel model was glycosylated haemoglobin concentration, in the midfoot Charcot deformity, in the forefoot prominent metatarsal heads, in the lesser toes hammer toe deformity and in the hallux previous ulceration. Variables with local effects (e.g. foot deformity were stronger predictors of plantar pressure than global features (e.g. body mass, age, gender, or diabetes duration.The presence of local deformity was the largest contributing factor to barefoot dynamic plantar pressure in high-risk diabetic patients and should therefore be adequately managed to reduce plantar pressure and ulcer risk. However, a significant amount of variance is unexplained by the models, which advocates the quantitative measurement of plantar pressures in the clinical risk assessment of the patient.

  8. {sup 123}I-MIBG lung uptake in patients with diabetes mellitus. Correlation with cardiac autonomic neuropathy

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    Nagamachi, Shigeki; Jinnouchi, Seishi; Flores, L.G. II; Ohnishi, Takashi; Tamura, Shozo; Watanabe, Katsushi; Kurose, Takeshi; Matsukura, Sigeru [Miyazaki Medical Coll., Kiyotake (Japan)

    1997-10-01

    The purpose of this study is to investigate the relationship between {sup 123}I-MIBG lung uptake and autonomic neuropathy (AN) in patients with diabetes mellitus. For the quantitative analysis, lung to upper mediastinum uptake ratio (L/M) and heart to upper mediastinum uptake ratio (H/M) were obtained from chest planar image. In addition, both lung washout ratio (%WR-L) and heart washout ratio (%WR-H) were calculated from early and delayed images. Similarly, exercised myocardial scintigraphy using {sup 201}Tl-chloride was done to rule out ischemia and lung to upper mediastinum uptake ratio (L/M-Tl) and heart to upper mediastinum uptake ratio (H/M-Tl) were obtained from chest planar image. Each indexes were compared in both diabetic group and control group. Both mean value of H/M and %WR-H in AN (+) group were significantly higher than those of control group. Mean value of L/M in each diabetic group was significantly higher than that of control group. Particularly, L/M of AN (+) group is higher than that of AN (-) group on early study. Mean value of %WR-L in AN (+) group was also significantly higher than that of control group. Regarding the {sup 201}Tl-uptake index, there was no statistical significance among in each group. The current study showed that abnormal pulmonary {sup 123}I-MIBG uptake in the lu