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Sample records for experimental 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)

    ... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Diabetic neuropathy is a peripheral nerve disorder caused by diabetes or poor blood sugar control. The most common ...

  3. Changes of sodium channel expression in experimental painful diabetic neuropathy.

    Science.gov (United States)

    Craner, Matthew J; Klein, Joshua P; Renganathan, Muthukrishnan; Black, Joel A; Waxman, Stephen G

    2002-12-01

    Although pain is experienced by many patients with diabetic neuropathy, the pathophysiology of painful diabetic neuropathy is not understood. Substantial evidence indicates that dysregulated sodium channel gene transcription contributes to hyperexcitability of dorsal root ganglion neurons, which may produce neuropathic pain after axonal transection. In this study, we examined sodium channel mRNA and protein expression in dorsal root ganglion neurons in rats with streptozotocin-induced diabetes and tactile allodynia, using in situ hybridization and immunocytochemistry for sodium channels Na(v)1.1, Na(v)1.3, Na(v)1.6, Na(v)1.7, Na(v)1.8, and Na(v)1.9. Our results show that, in rats with experimental diabetes, there is a significant upregulation of mRNA for the Na(v)1.3, Na(v)1.6, and Na(v)1.9 sodium channels and a downregulation of Na(v)1.8 mRNA 1 and 8 weeks after onset of allodynia. Channel protein levels display parallel changes. Our results demonstrate dysregulated expression of the genes for sodium channels Na(v)1.3, Na(v)1.6, Na(v)1.8, and Na(v)1.9 in dorsal root ganglion neurons in experimental diabetes and suggest that misexpression of sodium channels contributes to neuropathic pain associated with diabetic neuropathy.

  4. Diabetic Neuropathies

    Science.gov (United States)

    Russell, James W.; Zilliox, Lindsay A.

    2014-01-01

    Purpose of Review: This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. Recent Findings: New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. Summary: Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain. PMID:25299279

  5. Ghrelin reverses experimental diabetic neuropathy in mice

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    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.

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

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    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

    2017-05-01

    Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A 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 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. © 2017 by the American Diabetes Association.

  7. Protection of Trigonelline on Experimental Diabetic Peripheral Neuropathy

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    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.

  8. Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy.

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    Toth, Cory; Rong, Ling Ling; Yang, Christina; Martinez, Jose; Song, Fei; Ramji, Noor; Brussee, Valentine; Liu, Wei; Durand, Jeff; Nguyen, Minh Dang; Schmidt, Ann Marie; Zochodne, Douglas W

    2008-04-01

    Heightened expression of the receptor for advanced glycation end products (RAGE) contributes to development of systemic diabetic complications, but its contribution to diabetic neuropathy is uncertain. We studied experimental diabetic neuropathy and its relationship with RAGE expression using streptozotocin-induced diabetic mice including a RAGE(-/-) cohort exposed to long-term diabetes compared with littermates without diabetes. Structural indexes of neuropathy were addressed with serial (1, 3, 5, and 9 months of experimental diabetes) electrophysiological and quantitative morphometric analysis of dorsal root ganglia (DRG), peripheral nerve, and epidermal innervation. RAGE protein and mRNA levels in DRG, peripheral nerve, and epidermal terminals were assessed in WT and RAGE(-/-) mice, with and without diabetes. The correlation of RAGE activation with nuclear factor (NF)-kappaB and protein kinase C beta II (PKC beta II) protein and mRNA expression was also determined. Diabetic peripheral epidermal axons, sural axons, Schwann cells, and sensory neurons within ganglia developed dramatic and cumulative rises in RAGE mRNA and protein along with progressive electrophysiological and structural abnormalities. RAGE(-/-) mice had attenuated structural features of neuropathy after 5 months of diabetes. RAGE-mediated signaling pathway activation for NF-kappaB and PKC beta II pathways was most evident among Schwann cells in the DRG and peripheral nerve. In a long-term model of experimental diabetes resembling human diabetic peripheral neuropathy, RAGE expression in the peripheral nervous system rises cumulatively and relates to progressive pathological changes. Mice lacking RAGE have attenuated features of neuropathy and limited activation of potentially detrimental signaling pathways.

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

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    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.

  10. 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

    2012-09-01

    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.

  11. NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy.

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    Van Acker, Nathalie; Ragé, Michael; Vermeirsch, Hilde; Schrijvers, Dorien; Nuydens, Rony; Byttebier, Geert; Timmers, Maarten; De Schepper, Stefanie; Streffer, Johannes; Andries, Luc; Plaghki, Léon; Cras, Patrick; Meert, Theo

    2016-01-01

    The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes.

  12. Diabetic neuropathy: Part 2

    National Research Council Canada - National Science Library

    Gupta, Anu; Gupta, Yashdeep

    2014-01-01

    To conclude, effective management of hyperglycaemia, symptom control, and prevention of foot ulcers and infection through screening and surveillance remain mainstays of diabetic neuropathy management...

  13. [Diabetic neuropathy: do not only consider distal symmetrical neuropathy].

    Science.gov (United States)

    Doppler, K; Reiners, K

    2015-02-01

    Diabetic neuropathy is a common complication of diabetes mellitus. The length-dependent symmetrical sensorimotor type of neuropathy is the most prevalent form of diabetic neuropathy but other forms of diabetic neuropathy also need to be kept in mind. Their differential diagnosis is often more challenging but implicates specific forms of treatment other than improvement of metabolic control. This article gives an overview of the less frequent forms of diabetic neuropathy and discusses their impact, diagnostic and therapeutic implications. Autonomic diabetic neuropathy, diabetic small fiber neuropathy and less frequent forms of diabetic neuropathy, such as diabetic radiculoplexopathy, diabetic neuropathy of cranial nerves, therapy-induced neuropathy and alternative causes of peripheral neuropathy in patients with diabetes are described. Diagnosis of less frequent subtypes of diabetic neuropathy and differentiation towards alternative causes of peripheral neuropathy are often difficult in daily medical routine. Diagnostic clues are helpful in identifying rarer forms of diabetic neuropathy, thus enabling more specific treatment.

  14. PGC-1α Regulation of Mitochondrial Degeneration in Experimental Diabetic Neuropathy

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

    2014-01-01

    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. PMID:24423644

  15. 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......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

  16. Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy

    OpenAIRE

    Sekhar, Pagadala Nataraj; Kishor, P. B. Kavi; P. K. Zubaidha; Hashmi, A. M; Kadam, T. A.; Anandareddy, Lakkireddy; De Maeyer, Marc; Kumar, K. Praveen; Bhaskar, B. Vijaya; Munichandrababu, T; Jayasree, G; Narayana, P. V. B. S; Gyananath, G

    2011-01-01

    The enzyme aldoreductase which plays an important role in pathogenesis of diabetic retinopathy, neuropathy, and nephropathy was purified from bovine lens, and its inhibitory activity was studied with the synthesized flavone derivatives 1-(2-hydroxyphenyl)ethanone as the starting material. Experimental study revealed that 2-chloroflavone shows less inhibitory activity of 60-70% than other flavones used in the study. To validate experimental results computationally, docking studies of new flavo...

  17. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

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    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  18. Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy.

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    Patel, Sita Sharan; Udayabanu, M

    2013-09-27

    Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Experimental Anterior Ischemic Optic Neuropathy in Diabetic Mice Exhibited Severe Retinal Swelling Associated With VEGF Elevation.

    Science.gov (United States)

    Sun, Ming-Hui; Shariati, Mohammad Ali; Liao, Yaping Joyce

    2017-04-01

    Diabetes mellitus (DM) is one of the most important risk factors for nonarteritic anterior ischemic optic neuropathy (AION). In this study, we investigated for the first time the impact of experimental AION in a DM model. We induced a photochemical thrombosis model of AION after streptozotocin-induced DM and performed serial optical coherence tomography (OCT), morphometric analyses, and VEGF levels in the retina and sera. Compared with non-DM animals, experimental AION in DM mice led to significantly greater retinal swelling on day 1 and worse thinning at week 3 on OCT measurements. Greater retinal swelling on OCT in DM-AION eyes was associated with significantly increased loss of brain-specific homeobox/POU domain protein 3A (Brn3A+) retinal ganglion cells at week 3. In acute AION, there was greater inflammation as seen by an increase in ionized calcium-binding adapter molecule 1 (Iba1+)-activated microglia. On day 1, there was increase in vascular endothelial growth factor (VEGF) level in nondiabetic AION retinae and sera, but the VEGF level was the highest in the diabetic AION group, which decreased to nondiabetic levels after insulin treatment. The decrease in retinal and serum VEGF levels after insulin treatment correlated with a reduction in retinal swelling. In the setting of hyperglycemia, AION led to greater acute, postischemic microglial activation and elevation of VEGF levels, which likely contributed to greater retinal swelling acutely and worse retinal thinning and loss of retinal ganglion cells chronically. Treatment of hyperglycemia with insulin reduced VEGF levels and retinal swelling, consistent with the idea that VEGF is an important factor in postischemic swelling and that good glycemic control following AION may lead to better visual outcome.

  20. [Atypical neuropathies associated with diabetes].

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    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.

  1. Postural characteristics of diabetic neuropathy.

    Science.gov (United States)

    Oppenheim, U; Kohen-Raz, R; Alex, D; Kohen-Raz, A; Azarya, M

    1999-02-01

    To explore the posturographic correlates of diabetic neuropathy by comparing the performances of three groups of diabetic patients (severe, moderate, and absent neuropathy) with those of normal subjects and four clinical control groups. Using the Interactive Balance System (Tetrax, Ramat Gan, Israel), based on the assessment of the interaction of vertical pressure fluctuations on four independent platforms, one for each heel and toe part, respectively, posturographic examinations were given to 28 diabetic patients (8 with severe, 12 with moderate, and 8 with no peripheral neuropathy), 30 normal control subjects, and a clinical control group of 52 patients (14 with stage II Parkinson's disease, 13 with brain damage, 7 with whiplash, and 19 with peripheral vestibular pathology). The following posturographic parameters were evaluated; 1) general stability; 2) Fourier analysis showing patterns of sway intensity within eight frequency bands between 0.1 and 3 Hz; 3) weight distribution; 4) synchronization of sway; and 5) performance patterns for eight positions, requiring closure of eyes and standing on an elastic surface, as well as left, right, back, and downward head turns. For positions with closed eyes, diabetic patients with severe and moderate neuropathy were significantly less stable than normal subjects and diabetic patients without neuropathy, but diabetic patients with severe and moderate neuropathy turned out to be as equally unstable as clinical control subjects. However, for sway intensity within the band of 0.5 to 1.00 Hz on positions with lateral head turn with occluded vision, neuropathic diabetic patients performed significantly worse than did both normal and clinical control subjects. The same posturographic parameter also differed significantly between normal subjects and diabetic patients without neuropathy. As reported in previous studies, general instability in diabetic neuropathy is not a sufficiently characteristic correlate of the syndrome. On

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

    Directory of Open Access Journals (Sweden)

    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.

  3. ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

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    Giriraja Vrushabaiah Kanakapura

    2017-09-01

    Full Text Available BACKGROUND Diabetic neuropathy, retinopathy and nephropathy are the chronic complications of diabetes mellitus. Neuropathy, retinopathy and nephropathy are microvascular complication of diabetes mellitus. Antioxidant status is reduced in DM-induced retinopathy and nephropathy. Present study is undertaken to evaluate the degree of oxidative stress in diabetic neuropathy patients. The aim of the study is to study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde and antienzyme status in type II DM patients with neuropathy and compared them with a controlled nondiabetic group. MATERIALS AND METHODS The study included 100 subjects from Sapthagiri Medical College, Bangalore, from January 1, 2015, to December 31, 2015, of age group 50 to 70 yrs. out of which 50 patients were non-insulin-dependent DM with neuropathy and rest 50 age and sex matched apparently healthy individuals (control group. Antioxidant status was assessed by measuring superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, Catalase and Reduced Glutathione (GSH. RESULTS It showed a significant increase p<0.001 in FBS, PPBS, TC, TG, LDL, VLDL, CAT, MDA, while HDL, GSH, GPX, GR and SOD were found to be decreased significantly (p 0.001. CONCLUSION MDA was significantly elevated in diabetic group, whereas antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly decreased, which might be helpful in risk assessment of various complications of DM. The data suggests that alteration in antioxidant status and MDA may help to predict the risk of diabetic neuropathy.

  4. 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...... in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests....... diagnosis of CAN clinical forms, 2. detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, OH, nondipping, QT interval prolongation), 3. risk stratification for diabetic complications and cardiovascular morbidity and mortality, and 4. modulation of targets of diabetes therapy...

  5. Evaluation and Prevention of Diabetic Neuropathy

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    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.

  6. Pharmacological characterization of different fractions of Calotropis procera (Asclepiadaceae) in streptozotocin induced experimental model of diabetic neuropathy.

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    Yadav, Sandeep Kumar; Nagori, Badri Prakash; Desai, Prashant Kumar

    2014-03-14

    Calotropis procera (Ait.) R.Br. is one of an ancient traditional shrub, which has been used for the treatment of diabetes, pain and inflammation for thousands of years in India. The root extract of Calotropis procera has been widely used by the tribal׳s of district Udaipur, Rajasthan (India) for treatment of diabetes mellitus and its associated complications like diabetic neuropathy. The present study was performed to explore the protective effect of root, stem and leaf extracts of Calotropis procera in diabetes and diabetic neuropathy against tactile allodynia, mechanical hyperalgesia and thermal hyperalgesia in streptozotocin induced diabetic rats. Diabetes and peripheral neuropathy were induced in Wistar rats by injection of streptozotocin (45 mg/kg/intraperitoneally). The roots, stem and leaves of Calotropis procera were sequentially extracted with petroleum ether, chloroform, ethyl acetate and methanol. All the extracts were assessed by oral administration at 100 and 250 mg/kg in streptozotocin diabetic rats. The following compounds were used as positive controls: insulin NPH (1 IU/kg/day), metformin (500 mg/kg/day), glibenclamide (2.5 mg/kg/day) and a combination of acarbose (20 mg/kg/day) with methylcobalamine (500 µg/kg/day). In contrast, the streptozotocin induced untreated diabetic rats termed as negative control. Thermal hyperalgesia, mechanical hyperalgesia and tactile allodynia were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy by Eddy׳s hot plate, tail immersion, Randall-Selitto and Von Frey hair tests. The basal nociceptive thresholds were assessed in week 4 of post streptozotocin injection. All groups received their treatment on a regular basis from 28 to 42 days following a confirmation of diabetic neuropathy. The nociceptive thresholds were assessed in all groups in week 5 and 6. The histopathology of pancreas and biochemical estimations of plasma insulin and glycosylated haemoglobin (HbA1C%) levels

  7. 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.

    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

  8. Management of Diabetic Neuropathy: Focus on Patient

    Directory of Open Access Journals (Sweden)

    V.I. Pankiv

    2013-03-01

    Full Text Available The article highlights the questions of pathogenesis and treatment of diabetic neuropathy — one of the most frequent complications of diabetes mellitus. The effects of alpha-lipoic acid — first-line drug in the treatment of diabetic neuropathy — are considered in detail.

  9. 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).

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

    African Journals Online (AJOL)

    access article is distributed under. Creative Commons licence CC-BY-NC 4.0. CASE REPORT. Diabetic cachectic neuropathy: An uncommon neurological complication of diabetes. A Iyagba, MBBS, FWACP, FMCP; A Onwuchekwa, MBBS, FMCP.

  11. 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.

  12. 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......-neuropathic patients and in 16 individually matched control subjects. In the neuropathic patients the muscle strength of the ankle dorsal and plantar flexors was reduced by 41 % as compared to the non-neuropathic patients (p ... 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...

  13. Diabetic neuropathy: Clinical manifestations and current treatments

    Science.gov (United States)

    Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy is a prevalent, disabling condition. The most common manifestation is a distal symmetric polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control dramatically decreases the development of neuropathy in those with type 1 diabetes, the effect is likely much smaller in those with type 2 diabetes. High levels of evidence support the use of certain anticonvulsants and antidepressants for pain management in diabetic peripheral neuropathy. However, the lack of disease modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Intriguingly, growing evidence supports an association between metabolic syndrome components, including pre-diabetes, and neuropathy. Future studies are needed to further explore this relationship with implications for new treatments for this common disease. PMID:22608666

  14. Treatment of painful diabetic neuropathy

    Science.gov (United States)

    Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  15. Mouse Models of Diabetic Neuropathy

    Science.gov (United States)

    O'Brien, Phillipe D.; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. The mechanisms underlying DPN pathogenesis are uncertain, and other than tight glycemic control in type 1 patients, there is no effective treatment. Mouse models of type 1 (T1DM) and type 2 diabetes (T2DM) are critical to improving our understanding of DPN pathophysiology and developing novel treatment strategies. In this review, we discuss the most widely used T1DM and T2DM mouse models for DPN research, with emphasis on the main neurologic phenotype of each model. We also discuss important considerations for selecting appropriate models for T1DM and T2DM DPN studies and describe the promise of novel emerging diabetic mouse models for DPN research. The development, characterization, and comprehensive neurologic phenotyping of clinically relevant mouse models for T1DM and T2DM will provide valuable resources for future studies examining DPN pathogenesis and novel therapeutic strategies. PMID:24615439

  16. 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.

  17. Efficacy of α-lipoic acid in diabetic neuropathy.

    Science.gov (United States)

    Papanas, Nikolaos; Ziegler, Dan

    2014-12-01

    Neuropathy is a serious complication of diabetes. Its management focuses on glycaemic control, multifactorial cardiovascular risk intervention, pathogenesis-oriented therapy, and analgesics where needed. The objective of this review is assessment of efficacy and safety of α lipoic acid (ALA, also thioctic acid) in pathogenesis-oriented treatment of diabetic neuropathy. The mechanisms of action of ALA in experimental diabetic neuropathy include reduction of oxidative stress along with improvement in nerve blood flow, nerve conduction velocity, and several other measures of nerve function. There is ample evidence from randomised, double-blind, placebo-controlled clinical trials and meta-analyses, suggesting that ALA is efficacious and safe for the diabetic neuropathy, accomplishing clinically meaningful improvements. ALA is a valuable therapeutic option for diabetic neuropathy. When compared with currently licensed analgesic drugs, it is better tolerated, has a more rapid onset of action, and improves paraesthesiae, numbness, sensory deficits, and muscle strength in addition to neuropathic pain. In clinical practice, ALA may be chosen in patients with early neuropathic deficits and symptoms, in whom clinical improvement is more likely. ALA should also be considered when comorbidities render other analgesics less appropriate or in the presence of cardiovascular autonomic neuropathy.

  18. Association between MTHFR variant and diabetic neuropathy.

    Science.gov (United States)

    Kakavand Hamidi, Armita; Radfar, Mania; Amoli, Mahsa M

    2017-04-26

    Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an important role in the pathophysiology of diabetes and its complications due to its influence on plasma homocysteine levels and also its effect on scavenging peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to investigate the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A ⁄C polymorphisms. Patients with type 2 diabetes N=248 were enrolled in the study, consisting of patients with neuropathy (N=141) and patients without neuropathy (N=107). MTHFR C677T polymorphism was analyzed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) of genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using ARMS-PCR. There was a significant difference in MTHFR polymorphism between the groups with and without neuropathy. Our results suggest that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients with type 2 diabetes. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Treatment of painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Rosenberg, Casandra J; Watson, James C

    2015-02-01

    Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

  20. APOE gene polymorphisms and diabetic peripheral neuropathy

    Science.gov (United States)

    Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-01-01

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes. PMID:23056065

  1. Autologous Bone Marrow-Derived Stem Cells for Treating Diabetic Neuropathy in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2017-01-01

    Full Text Available Diabetic neuropathy is one of the most common and serious complications of diabetes mellitus and metabolic syndrome. The current therapy strategies, including glucose control and pain management, are not effective for most patients. Growing evidence suggests that infiltration of inflammation factors and deficiency of local neurotrophic and angiogenic factors contribute significantly to the pathologies of diabetic neuropathy. Experimental and clinical studies have shown that bone marrow-derived stem cells (BMCs therapy represents a novel and promising strategy for tissue repair through paracrine secretion of multiple cytokines, which has a potential to inhibit inflammation and promote angiogenesis and neurotrophy in diabetic neuropathy. In this review, we discuss the clinical practice in diabetic neuropathy and the therapeutic effect of BMC. We subsequently illustrate the functional impairment of autologous BMCs due to the interrupted bone marrow niche in diabetic neuropathy. We anticipate that the functional restoration of BMCs could improve their therapeutic effect and enable their wide applications in diabetic neuropathy.

  2. Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions.

    Science.gov (United States)

    Visnagri, Asjad; Kandhare, Amit D; Chakravarty, Shalendra; Ghosh, Pinaki; Bodhankar, Subhash L

    2014-07-01

    Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats. DN was induced in Sprague-Dawley rats (150-200 g) by intraperitoneal administration of streptozotocin (STZ) (55 mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100 mg/kg, p.o.), insulin (10 IU/kg, s.c.), and combination of hesperidin (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na-K-ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1β) along with hemodynamic changes were determined. Rats treated with hesperidin (50 and 100 mg/kg, p.o., 4 weeks) significantly reduced (p hesperidin (50 and 100 mg/kg, p.o.) treatment. It significantly attenuated (p hesperidin (50 and 100 mg/kg, p.o.) In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.

  3. [Pathogenesis and treatment of diabetic neuropathy].

    Science.gov (United States)

    Grzelec, H

    1991-01-01

    The pathogenesis of neuropathy and other late, degenerative complications of diabetes remains largely unresolved. Metabolic derangements thought to be responsible for their development are induced by chronic hyperglycaemia. The present studies concern as follows: sorbitol accumulation due to increased polyol pathway activity, altered myoinositol metabolism in diabetic nerve, followed by diminished sodium-potassium ATPase activity, nonenzymatic glycosylation of structural proteins and rheologic changes in microcirculation. These processes impair nerve metabolism, function and structure directly or indirectly, due to primary vascular alternations and endoneural hypoxia. Partial elucidation of the mechanism involved in pathogenesis of diabetic neuropathy has provoked emergence of new therapeutic approaches. So far their results are equivocal and require further studies. At present, improved glycaemia control is undoubtedly the most important factor in prevention and treatment of neuropathy and other late complications of diabetes.

  4. 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...... 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...

  5. Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Sangeetha Srinivasan

    2017-10-01

    Conclusions: The GCC FLV can differentiate individuals with diabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be required to identify patients with minimal neuropathy.

  6. Cardiac Autonomic Neuropathy and QTc Interval in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jayaprasad Narayana Pillai

    2015-01-01

    Full Text Available Context: An association between cardiac autonomic neuropathy and QT interval prolongation was demonstrated in many studies and it may predispose to sudden death in diabetes mellitus. Aims: To find out the prevalence of cardiac autonomic neuropathy and its relation to QTc interval and QTc dispersion in type 2 diabetes. Settings and Design: Observational study. Materials and Methods: Fifty patients with type 2 diabetes mellitus of more than 5-years duration and 30 age- and sex-matched controls without any history of diabetes were selected. A battery of five autonomic function tests was done in all cases. Heart rate, QTc values, and QTc dispersion were measured and compared among patients with and without autonomic neuropathy and controls. Statistical analysis used: Students t test/Chi-square test. Results: Among the 50 patients in the study population, 21 (42% had severe autonomic neuropathy and 12 (24% had early autonomic neuropathy. Mean heart rate was significantly more in patients with autonomic neuropathy than those without neuropathy. Diabetics with autonomic neuropathy had significantly higher QTc mean and QTc max values compared to diabetics without autonomic neuropathy and controls. QTc dispersion was significantly more among patients with autonomic neuropathy compared to those without autonomic neuropathy and controls. Conclusions: Diabetic autonomic neuropathy is associated with increase in resting heart rate and prolongation of QTc intervals. QTc max was correlating with severity of autonomic neuropathy. QTc dispersion is significantly high in diabetes mellitus with autonomic neuropathy.

  7. Beneficial effect of an ACTH4-9 analogue on experimentally induced diabetic autonomic neuropathy in the eye of the rat under general anaesthesia

    NARCIS (Netherlands)

    Vandertop, W. P.; de Vries, W. B.; Notermans, N. C.; Tulleken, C. A.; Gispen, W. H.

    1995-01-01

    While peripheral polyneuropathy is a well-known complication in diabetes mellitus, and the subject of a great deal of study, the clinical importance of autonomic diabetic neuropathy is increasingly recognised. Using an animal model, where the pupil diameter of the eye serves as a parameter of

  8. DIABETIC NEUROPATHY PART 1: OVERVIEW AND SYMMETRIC PHENOTYPES

    Science.gov (United States)

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

    2014-01-01

    Diabetes is the most common cause of neuropathy in US and neuropathies are the most common complication of diabetes mellitus affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Various types of neuropathies can be associated with diabetes mellitus.1 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. Pathologically 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. Many medications are available for the treatment of neuropathic pain. PMID:23642717

  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. Diabetic peripheral neuropathy, is it an autoimmune disease?

    Science.gov (United States)

    Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

    2015-11-01

    Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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

  12. Blood pressure regulation in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1985-01-01

    Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... 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....

  13. 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.

  14. Diabetic Driving Studies-Part 1: Brake Response Time in Diabetic Drivers With Lower Extremity Neuropathy.

    Science.gov (United States)

    Meyr, Andrew J; Spiess, Kerianne E

    Although the effect of lower extremity pathology and surgical intervention on automobile driving function has been a topic of contemporary interest, we are unaware of any analysis of the effect of lower extremity diabetic sensorimotor neuropathy on driving performance. The objective of the present case-control investigation was to assess the mean brake response time in diabetic drivers with lower extremity neuropathy compared with that of a control group and a brake response safety threshold. The driving performances of participants were evaluated using a computerized driving simulator with specific measurement of the mean brake response time and frequency of abnormally delayed brake responses. We analyzed a control group of 25 active drivers with neither diabetes nor lower extremity neuropathy and an experimental group of 25 active drivers with type 2 diabetes and lower extremity neuropathy. The experimental group demonstrated a 37.89% slower mean brake response time (0.757 ± 0.180 versus 0.549 ± 0.076 second; p diabetic patients with lower extremity neuropathy and might raise the potential for impaired driving function in this population. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Does Endurance Training Compensate for Neurotrophin Deficiency Following Diabetic Neuropathy?

    Science.gov (United States)

    Eslami, Rasoul; Gharakhanlou, Reza; Kazemi, Abdolreza; Dakhili, Amir Bahador; Sorkhkamanzadeh, Ghazaleh; Sheikhy, Ayob

    2016-10-01

    A lack of neurotrophic support is believed to contribute to the development of diabetic neuropathy. On the other hand, neurotrophins have consistently been shown to increase in the central and peripheral nervous system following exercise, but the effects of exercise intervention on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in diabetic neuropathy are not understood. This experimental study was designed and carried out at the Tarbiat Modares university (TMU) in Tehran, Iran, to investigate the hypothesis that increased activity as endurance training can help to increase the endogenous expression of neurotrophins in diabetic rats. This was an experimental study with 2 × 2 factorial plans performed at TMU in Iran. Sampling was accidental and 28 adult male Wistar rats in the body mass range of 326.3 ± 8.4 g comprised the sample, with each rat randomly assigned to four groups: diabetic control (DC), diabetic training (DT), healthy control (HC), and healthy training (HT). To induce diabetic neuropathy, after 12 hours of food deprivation, an intraperitoneal injection of streptozotocin (STZ) solution (45 mg/Kg) method was used. Two weeks after STZ injection, the endurance training protocol was performed for 6 weeks; 24 hours after the last training session, the rats were sacrificed. Real-time PCR was used for BDNF and NGF expression. The data indicate that diabetes decreases BDNF and NGF expression in sensory (92%, P = 0.01; 90%, P = 0.038, respectively) and motor (93%, P = 0.05; 60%, P = 0.029, respectively) roots. However, NGF mRNA levels in the DT group were significantly higher than in the HC group ((7.1-fold), P = 0.01; (2.2-fold), P = 0.001, respectively, for sensory and motor roots), but this was not shown for BDNF. In addition, endurance training can increase NGF expression in healthy rats ((7.4-fold), P = 0.01; (3.8-fold), P = 0.001, respectively, for sensory and motor roots). This study shows that BDNF and NGF expression decreases in

  16. Treatment of diabetic neuropathy in the lower limb

    African Journals Online (AJOL)

    The classic signs of motor neuropathy are a high medial arch, claw toes and metatarsal head prominence with fatty pad thinning. Symptoms of autonomic neuropathy in the diabetic foot usually include dry, cracked skin, nail changes, transient mottling and discoloration of the skin and cold feet. Confirmed clinical neuropathy ...

  17. Diabetic neuropathy and painful diabetic neuropathy: Cinderella complications in South East Asia.

    Science.gov (United States)

    Almuhannadi, Hamad; Ponirakis, Georgios; Khan, Adnan; Malik, Rayaz Ahmed

    2018-01-01

    The most common and debilitating microvascular complication of diabetes is diabetic peripheral neuropathy (DPN), affecting 50-90% of people with diabetes. The major manifestations of DPN are painful (pDPN) and painless diabetic peripheral neuropathy. Painful symptoms, occur in the feet and are worse at night and whilst they alert both the patient and physician, are often misdiagnosed and mismanaged. The devastating presentation of painless neuropathy with loss of sensation is foot ulceration and Charcot foot. The explosion of diabetes, especially in the South East Asian (SEA) region will result in an increasing prevalence of both painful and painless diabetic peripheral neuropathy. PubMed, EMBASE, Medline and Google Scholar databases were searched between 1990 and 2017. This highlights the widely varying prevalence of DPN and pDPN in the World Health Organization (WHO) defined SEA countries and the dearth of published studies, especially in pDPN. We believe this will provide new direction for future research on DPN in the SEA region.

  18. 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...

  19. Focal loss volume of ganglion cell complex in diabetic neuropathy.

    Science.gov (United States)

    Srinivasan, Sangeetha; Pritchard, Nicola; Sampson, Geoff P; Edwards, Katie; Vagenas, Dimitrios; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2016-11-01

    The aim was to investigate the relationship between diabetic peripheral neuropathy (DPN) and abnormalities in ganglion cell complex (GCC); specifically, focal loss volume (FLV) and global loss volume (GLV). The ganglion cell complex was evaluated using optical coherence tomography on 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes and 42 without diabetes). In those with diabetes, 88 had diabetes but no diabetic retinopathy (no DR group) and 63 had diabetes with diabetic retinopathy (DR group). Seventeen individuals in the no DR group and 27 in the DR group had diabetic peripheral neuropathy according to the neuropathy disability score (NDS). The probability of FLV and GLV being abnormal was determined. Forty four individuals had diabetic peripheral neuropathy (NDS of three or greater). Binary logistic regression analysis was performed, adjusting for the presence of diabetic retinopathy, age, sex, type of diabetes, duration of diabetes and HbA1c levels. Twenty-five per cent of individuals with diabetic peripheral neuropathy had abnormal FLV compared to 11 per cent of those with diabetes but no diabetic peripheral neuropathy and five per cent in the control group (p = 0.011). Fourteen per cent of individuals with diabetic peripheral neuropathy, 10 per cent without diabetic peripheral neuropathy and two per cent in the control group had abnormal GLV (p = 0.185). For every unit increase in the neuropathy disability score, the odds of having an abnormal FLV increased by a factor of 1.25 (p = 0.007), after adjusting for potentially confounding factors. Abnormal GCC FLV is an independent predictor of diabetic neuropathy, (odds ratio = 2.94, 95 per cent CI [1.16, 7.40], p = 0.023). Diabetic peripheral neuropathy is associated with abnormal GCC FLV at the macula, which is independent of diabetic retinopathy, age, sex, type of diabetes, duration of diabetes and HbA1c levels. An abnormality in GCC FLV is an independent predictor of diabetic peripheral

  20. 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.

  1. Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy

    NARCIS (Netherlands)

    ten Hoope, Werner; Hollmann, Markus W.; de Bruin, Kora; Verberne, Hein J.; Verkerk, Arie O.; Tan, Hanno L.; Verhamme, Camiel; Horn, Janneke; Rigaud, Marcel; Picardi, Susanne; Lirk, Philipp

    2017-01-01

    Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim

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

    National Research Council Canada - National Science Library

    Kambiz, Shoista; Neck, Han; Cosgun, Saniye G; Velzen, M. H N; Janssen, Joseph; Avazverdi, N; Hovius, Steven; Walbeehm, Erik

    2015-01-01

    ... diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats' hind paws...

  3. Antioxidant Strategies in the Management of Diabetic Neuropathy

    Science.gov (United States)

    Oyenihi, Ayodeji Babatunde; Ayeleso, Ademola Olabode; Masola, Bubuya

    2015-01-01

    Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. PMID:25821809

  4. Diabetic Neuropathy | Enesi | Journal of the Obafemi Awolowo ...

    African Journals Online (AJOL)

    Diabetes is a chronic metabolic disorder characterized by persistent hyperglycaemia. The prevalence of diabetes is increasing in epidemic proportions worldwide. Diabetic neuropathy is a common clinical complication of Diabetes mellitus, as almost all of diabetic patients will have some form of nerve damage. Majority are ...

  5. 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.

  6. Clinical manifestations and current treatment options for diabetic neuropathies.

    Science.gov (United States)

    Casellini, Carolina M; Vinik, Aaron I

    2007-09-01

    To review the clinical manifestations and current treatment options for diabetic neuropathies, one of the most common complications of diabetes mellitus. We performed a MEDLINE search of the English-language literature using a combination of words (diabetic neuropathy, diabetic autonomic neuropathy, diagnosis and treatment) to identify original studies, consensus statements, and reviews on diabetic neuropathies published in the past 25 years. Emphasis was placed on clinical manifestations of distal polyneuropathy and its treatment, especially new therapies. Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve fiber neuropathy often presents with pain and loss of intraepidermal nerve fibers, but without objective signs or electrophysiologic evidence of nerve damage. This type of neuropathy is a component of impaired glucose tolerance and the metabolic syndrome. The greatest risk from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve fiber neuropathy produces numbness, ataxia, and incoordination, thus impairing activities of daily living and causing falls and fractures. Successfully treating diabetic neuropathy requires addressing the underlying pathogenic mechanisms, treating symptoms to improve quality of life, and preventing progression and complications of diabetes mellitus. Two new drugs, duloxetine hydrochloride and pregabalin, have recently been approved for treatment of neuropathic pain associated with diabetes mellitus. Symptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for clinically significant reduction of morbidity and mortality. Preventive strategies and patient and physician education still remain key factors in reducing complication rates and mortality.

  7. 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 (Pdiabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  8. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 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. © 2016 Elsevier Inc. All rights reserved.

  10. Corneal Sensitivity as a Potential Marker of Diabetic Neuropathy.

    Science.gov (United States)

    Sitompul, Ratna

    2017-04-01

    Diabetes mellitus (DM) is a complex and chronic metabolic disorder leading to many complications. One of the most common complications of DM is diabetic neuropathy. There are many studies exploring corneal sensitivity as a potential marker of diabetic neuropathy. This review aims to explore association between corneal sensitivity and diabetic neuropathy. In diabetic neuropathy, corneal sensitivity is impaired due to low level of corneal nerve trophic factors, impaired sensory nerve fibers, and lost communication of dendtritic cell. In diabetic patients, this condition can be assessed by several techniques, such as Cochet Bonnet aesthesiometry, non-contact corneal aesthesiometry, and confocal microscopy. Few promising therapeutic targets for impaired corneal sensitivity include stem cell and growth factor therapy that can be used to prevent complication in patient with diabetic neurotrophic keratopathy. Impaired corneal sensitivity serve as a potential marker of diabetic neuropathy. Doctors, opthalmologists and internists, should anticipate the possibility of observing the following changes in diabetic patients with neuropathy by using corneal sensitivity assessment test.

  11. 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.

  12. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes

    National Research Council Canada - National Science Library

    Gibbons, Christopher H; Freeman, Roy

    2015-01-01

    Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia...

  13. 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...

  14. Decreased myocardial perfusion reserve in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

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

    2002-01-01

    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......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......(i)) was similar in the three groups (AN+ 88.6 +/- 8.7 ml. 100 g(-1). min(-1), AN- 82.6 +/- 7.2, control subjects 93.7 +/- 9.0) (means +/- SE). K(i) during Dipyridamole vasodilatation was significantly lower in the patients with autonomic neuropathy (P

  15. Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy.

    Science.gov (United States)

    Srinivasan, Sangeetha; Pritchard, Nicola; Sampson, Geoff P; Edwards, Katie; Vagenas, Dimitrios; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    To examine the diagnostic capability of the full retinal and inner retinal thickness measures in differentiating individuals with diabetic peripheral neuropathy (DPN) from those without neuropathy and non-diabetic controls. Individuals with (n=44) and without (n=107) diabetic neuropathy and non-diabetic control (n=42) participants underwent spectral domain optical coherence tomography (SDOCT). Retinal thickness in the central 1mm zone (including the fovea), parafovea and perifovea was assessed in addition to ganglion cell complex (GCC) global loss volume (GCC GLV) and focal loss volume (GCC FLV), and retinal nerve fiber layer (RNFL) thickness. Diabetic neuropathy was defined using a modified neuropathy disability score (NDS) recorded on a 0-10 scale, wherein, NDS ≥3 indicated neuropathy and NDS indicated neuropathy. Diagnostic performance was assessed by areas under the receiver operating characteristic curves (AUCs), 95 per cent confidence intervals (CI), sensitivities at fixed specificities, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the cut-off points for the best AUCs obtained. The AUC for GCC FLV was 0.732 (95% CI: 0.624-0.840, pneuropathy from those without neuropathy, the AUCs of retinal parameters ranged from 0.508 for the central zone to 0.690 for the inferior RNFL thickness. For distinguishing those with moderate or advanced neuropathy from those with mild or no neuropathy, the inferior RNFL thickness demonstrated the highest AUC of 0.820, (95% CI: 0.731-0.909, pdiabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be

  16. Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.

    Science.gov (United States)

    Miranda, H F; Sierralta, F; Jorquera, V; Poblete, P; Prieto, J C; Noriega, V

    2017-02-01

    Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ). The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice. STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test. The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.

  17. Neurotrophin-3 is increased in skin in human diabetic neuropathy

    Science.gov (United States)

    Kennedy, A; Wellmer, A; Facer, P; Saldanha, G; Kopelman, P; Lindsay, R; Anand, P

    1998-01-01

    Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models.The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32(1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30(0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.

 PMID:9728960

  18. Mobile phone generated vibrations used to detect diabetic peripheral neuropathy.

    Science.gov (United States)

    May, Jonathan David; Morris, Matthew William John

    2017-12-01

    In the current United Kingdom population the incidence of diabetic peripheral neuropathy is increasing. The presence of diabetic neuropathy affects decision making and treatment options. This study seeks to evaluate if the vibrations generated from a mobile phone can be used to screen patients for diabetic peripheral neuropathy. This study comprised of 61 patients; a control group of 21 patients; a lower limb injury group of 19 patients; a diabetic peripheral neuropathy group of 21 patients. The control and injury group were recruited randomly from fracture clinics. The diabetic peripheral neuropathy group were randomly recruited from the diabetic foot clinic. The 61 patients were examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a vibrating mobile phone. The points tested were, index finger, patella, lateral malleoli, medial malleoli, heel, first and fifth metatarsal heads. The most accurate location of all the clinical tests was the head of the 1st metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The neuropathic group felt 216 of 441 tests (48%). There is a significant difference in the number of tests felt between the control and both the injury and neuropathic groups. pdiabetic peripheral neuropathy. The most accurate location to test for diabetic peripheral neuropathy is the head of the 1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger and patella were inaccurate. An injury to the lower limb affects the patient's vibration sensation, we would therefore recommend screening the contralateral limb to the injury. This study represents level II evidence of a new diagnostic investigation. Copyright © 2016 European Foot and Ankle Society. All rights reserved.

  19. Monofilament assessment of neuropathy in a community diabetes ...

    African Journals Online (AJOL)

    Objective. To compare the detection of diabetic neuropathy using monofilament, cotton wool, pinprick, vibration sense and symptom evaluation. Setting. The diabetes clinic of a community hospital. Methods. Two examiners evaluated 89 women with diabetes mellitus (DM) using a 10 g monofilament, cotton wool, pinprick ...

  20. Treatment of diabetic neuropathy in the lower limb: Signs and ...

    African Journals Online (AJOL)

    Diabetic peripheral neuropathy (DPN) is defined as 'the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes: the diagnosis cannot be made without a clinical examination'. In fact, many of these symptoms and signs may precede the onset of diabetes.

  1. 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

  2. Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy.

    Science.gov (United States)

    Ten Hoope, Werner; Hollmann, Markus W; de Bruin, Kora; Verberne, Hein J; Verkerk, Arie O; Tan, Hanno L; Verhamme, Camiel; Horn, Janneke; Rigaud, Marcel; Picardi, Susanne; Lirk, Philipp

    2017-12-15

    Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes. We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity. First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons. We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.

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

    Science.gov (United States)

    Kumar, Anil; Mittal, Ruchika

    2017-08-01

    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.

  4. Fifteen-day acupuncture treatment relieves diabetic peripheral neuropathy.

    Science.gov (United States)

    Tong, Yanqing; Guo, Hongyang; Han, Bing

    2010-06-01

    Our study aimed to investigate the effects of acupuncture on diabetic peripheral neuropathy. We compared 42 cases treated with acupuncture with 21 cases exposed to sham acupuncture and observed the effects on nerve conduction velocity and a variety of subjective symptoms associated with diabetic peripheral neuropathy. Three of the six measures of motor nerves, and two measures of sensory function, demonstrated significant improvement (p day treatment period in the acupuncture group, while no motor or sensory function significantly improved in the sham acupuncture group. There were also significant differences in vibration perception threshold between the groups (p neuropathy. Copyright 2010 Korean Pharmacopuncture Institute. Published by .. All rights reserved.

  5. 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

  6. Gender differences in the onset of diabetic neuropathy.

    Science.gov (United States)

    Aaberg, Melanie L; Burch, Draion M; Hud, Zarinah R; Zacharias, Michael P

    2008-01-01

    Diabetic neuropathy is one of the more common complications plaguing individuals with type 2 diabetes. The development and progression of such complications are responsible for much of the morbidity and mortality related to this disease. Few studies have evaluated age at onset of diabetic neuropathy between genders. A difference in the progression of diabetic neuropathy between men and women may exist. This investigation evaluated gender differences in the age at onset of neuropathy among patients with type 2 diabetes. The study, a retrospective chart analysis, reviewed 376 inpatient and outpatient medical records between January 2004 and January 2006 from a Cleveland, Ohio, hospital. Onset of neuropathy was determined by the date the neuropathy International Classification of Diseases, Ninth Revision code was first included in the medical chart; for this study, onset was equated with the date of first identification. Data were analyzed via a tailed independent t test. Of the 376 inpatient and outpatient charts reviewed, 156 were for male patients and 220 were for female patients (41% and 59%, respectively). All patients had type 2 diabetes; however, 23% (n=86) required insulin therapy at the time of the study. Males developed neuropathic complications at 63 years, approximately 4 years earlier than did females (at 67 years). The t test revealed a statistically significant difference in age at onset of diabetic neuropathy between the male and female subjects. This study demonstrates that the males in the study population developed neuropathy earlier than did the females. It may then be hypothesized that earlier interventions in the male population may improve disease outcomes.

  7. The quest for more research on painful diabetic neuropathy.

    Science.gov (United States)

    Nawroth, P P; Bendszus, M; Pham, M; Jende, J; Heiland, S; Ries, S; Schumann, C; Schmelz, M; Schuh-Hofer, S; Treede, R D; Kuner, R; Oikonomou, D; Groener, J B; Kopf, S

    2017-09-20

    A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Distinct Effector Mechanisms in the Development of Autoimmune Neuropathy versus Diabetes in Nonobese Diabetic Mice

    National Research Council Canada - National Science Library

    Bour-Jordan, Helene; Thompson, Heather L; Bluestone, Jeffrey A

    2005-01-01

    ...) are protected from autoimmune diabetes but develop a spontaneous autoimmune peripheral neuropathy that resembles human diseases Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy...

  9. Single-fiber electromyography of facial and limb muscles in diabetic patients with or without neuropathy.

    Science.gov (United States)

    Al-Hashel, Jasem Y; Rousseff, Rossen T; Khuraibet, Adnan J; Tzvetanov, Plamen

    2014-10-01

    In diabetic patients, single-fiber electromyography (SFEMG) is often abnormal in the limb muscles and is considered unreliable in diagnosis of synaptic disorders. We aimed to compare SFEMG abnormalities of frontalis muscle (FM) and extensor digitorum communis muscle in diabetic patients with neuropathy and without neuropathy. Stimulation SFEMG of FM and extensor digitorum communis muscle was performed in matched groups of 30 diabetic patients with neuropathy and 20 diabetic patients without neuropathy. Single-fiber electromyography in the FM was abnormal in four diabetic patients with neuropathy and in one diabetic patient without neuropathy. Changes were rather mild. Extensor digitorum communis abnormalities were significantly more frequent-in 20 diabetic patients with neuropathy and in 7 diabetic patients without neuropathy (P diabetes, FM exhibits rare and quite mild SFEMG changes. This muscle may be suitable for SFEMG in diabetic patients with clinical suspicion for synaptic disorder.

  10. A novel curcumin derivative for the treatment of diabetic neuropathy.

    Science.gov (United States)

    Daugherty, Daniel J; Marquez, Alexandra; Calcutt, Nigel A; Schubert, David

    2018-02-01

    Neuropathy is a common complication of long-term diabetes. Proposed mechanisms of neuronal damage caused by diabetes that are downstream of hyperglycemia and/or loss of insulin signaling include ischemic hypoxia, inflammation and loss of neurotrophic support. The curcumin derivative J147 is a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy. Here, we demonstrate efficacy of J147 in ameliorating multiple indices of neuropathy in the streptozotocin-induced mouse model of type 1 diabetes. Diabetes was determined by blood glucose, HbA1c, and insulin levels and efficacy of J147 by behavioral, physiologic, biochemical, proteomic, and transcriptomic assays. Biological efficacy of systemic J147 treatment was confirmed by its capacity to decrease TNFα pathway activation and several other markers of neuroinflammation in the CNS. Chronic oral treatment with J147 protected the sciatic nerve from progressive diabetes-induced slowing of large myelinated fiber conduction velocity while single doses of J147 rapidly and transiently reversed established touch-evoked allodynia. Conduction slowing and allodynia are clinically relevant markers of early diabetic neuropathy and neuropathic pain, respectively. RNA expression profiling suggests that one of the pathways by which J147 imparts its protection against diabetic induced neuropathy may be through activation of the AMP kinase pathway. The diverse biological and therapeutic effects of J147 suggest it as an alternative to the polypharmaceutical approaches required to treat the multiple pathogenic mechanisms that contribute to diabetic neuropathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

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

    Science.gov (United States)

    Islam, Md. Shahidul

    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 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. PMID:23984428

  13. Nephropathy and Neuropathy in Diabetic Patients with Chronic ...

    African Journals Online (AJOL)

    Introduction: Several reports described an association between type 2 diabetes mellitus (DM) and chronic hepatitis C virus (HCV) infection. Chronic HCV infection is prevalent in Egypt. The present work aimed to evaluate the prevalence of proteinuria and neuropathy among diabetic patients with and without chronic HCV ...

  14. Diagnostic accuracy of laser-evoked potentials in diabetic neuropathy.

    Science.gov (United States)

    Di Stefano, Giulia; La Cesa, Silvia; Leone, Caterina; Pepe, Alessia; Galosi, Eleonora; Fiorelli, Marco; Valeriani, Massimiliano; Lacerenza, Marco; Pergolini, Mario; Biasiotta, Antonella; Cruccu, Giorgio; Truini, Andrea

    2017-06-01

    Although the most widely agreed neurophysiological tool for investigating small fiber 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 fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber 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-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber 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 fiber 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 fiber neuropathy.

  15. 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...

  16. 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. © 2016 Wiley Periodicals, Inc.

  17. Does Peripheral Neuropathy Associate with Cranial Nerves Neuropathy in Type 2 diabetes Patients?

    Directory of Open Access Journals (Sweden)

    Walaa Fadhil Jalal

    2017-02-01

    Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.

  18. 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. © 2014 Peripheral Nerve Society.

  19. Cold immersion recovery responses in the diabetic foot with neuropathy.

    Science.gov (United States)

    Bharara, Manish; Viswanathan, Vijay; Cobb, Jonathan E

    2008-10-01

    The aim of this article was to investigate the effectiveness of testing cold immersion recovery responses in the diabetic foot with neuropathy using a contact thermography system based on thermochromic liquid crystals. A total of 81 subjects with no history of diabetic foot ulceration were assigned to neuropathy, non neuropathy and healthy groups. Each group received prior verbal and written description of the test objectives and subsequently underwent a comprehensive foot care examination. The room temperature and humidity were consistently maintained at 24 degrees C and less than 50%, respectively, with air conditioning. The right foot for each subject was located on the measurement platform after cold immersion in water at 18-20 degrees C. Whole-field thermal images of the plantar foot were recorded for 10 minutes. Patients with diabetes with neuropathy show the highest 'delta temperature', that is difference between the temperature after 10-minute recovery period and baseline temperature measured independently at all the three sites tested, that is first metatarsal head (MTH), second MTH and heel. This clinical study showed for the first time the evidence of poor recovery times for the diabetic foot with neuropathy when assessing the foot under load. A temperature deficit (because of poor recovery to baseline temperature) suggests degeneration of thermoreceptors, leading to diminished hypothalamus-mediated activity in the diabetic neuropathic group.

  20. [Toronto clinical scoring system in diabetic peripheral neuropathy].

    Science.gov (United States)

    Liu, Feng; Mao, Ji-Ping; Yan, Xiang

    2008-12-01

    To evaluate the application value of Toronto clinical scoring system (TCSS) and its grading of neuropathy for diabetic peripheral neuropathy (DPN), and to explore the relationship between TCSS grading of neuropathy and the grading of diabetic nephropathy and diabetic retinopathy. A total of 209 patients of Type 2 diabtes (T2DM) underwent TCSS. Taking electrophysiological examination as a gold standard for diagnosing DPN, We compared the results of TCSS score > or = 6 with electrophysiological examination, and tried to select the optimal cut-off points of TCSS. The corresponding accuracy, sensitivity, and specificity of TCSS score > or = 6 were 76.6%, 77.2%, and 75.6%, respectively.The Youden index and Kappa were 0.53 and 0.52, which implied TCSS score > or = 6 had a moderate consistency with electrophysiological examination. There was a linear positive correlation between TCSS grading of neuropathy and the grading of diabetic nephropathy and diabetic retinopathy (P<0.05). The optimal cut-off point was 5 or 6 among these patients. TCSS is reliable in diagnosing DPN and its grading of neuropathy has clinical value.

  1. Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes

    National Research Council Canada - National Science Library

    Tahrani, Abd A; Ali, Asad; Raymond, Neil T; Begum, Safia; Dubb, Kiran; Mughal, Shanaz; Jose, Biju; Piya, Milan K; Barnett, Anthony H; Stevens, Martin J

    2012-01-01

    ...) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes...

  2. 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....

  3. Is Fish Oil a Potential Treatment for Diabetic Peripheral Neuropathy?

    Science.gov (United States)

    Yorek, Mark Anthony

    2017-05-22

    Peripheral neuropathy affects about 50% of the diabetic population. The manifestations range from pain, numbness, paresthesia and ulceration in the extremities and it is the major cause of non-traumatic amputations. Currently there is no effective treatment for peripheral neuropathy. With the prevalence of obesity and type 2 diabetes and associated complications reaching epidemic levels there is a critical need for finding a treatment to preserve nerve function. This article will review the potential for fish oil as a treatment for diabetic peripheral neuropathy. A through search of the PubMed database was performed and relevant articles on the topic were included in this review. Many studies support a role for fish oil in cardiovascular health. However, less information is available regarding the effect of fish oil on diabetes complications including neuropathy. Pre-clinical studies from my laboratory using diabetic rodent models have demonstrated that fish oil can slow progression and reverse diabetic neuropathy as determined by examining multiple endpoints. Mechanistically fish oil has been shown to have anti-inflammatory properties. Lowering the omega-6/omega-3 fatty acid ratio has been shown to be anti-thrombotic. Moreover, metabolites of eicosapentaenoic and docosahexaenoic acids, the main polyunsaturated fatty acids found in fish oil, commonly referred to as resolvins and neuroprotectin have been shown to be neuroprotective and can stimulate neuron outgrowth in vitro. Additional studies are required but existing data suggests that dietary enrichment with omega-3 fatty acids contained in fish oil may be beneficial treatment for diabetic neuropathy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. 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...

  5. Tactile direction discrimination and vibration detection in diabetic neuropathy.

    Science.gov (United States)

    Löken, Linda S; Lundblad, L C; Elam, M; Olausson, H W

    2010-05-01

    To evaluate the clinical usefulness of quantitative testing of tactile direction discrimination (TDD) in patients with diabetic neuropathy. TDD and vibration detection were examined on the dorsum of the feet in 43 patients with type 1 diabetes mellitus and clinical signs and symptoms indicating mild neuropathy, and abnormal results for neurography, temperature detection, or heart rate variability. Test-retest examination of TDD was performed in nine of the patients. Twenty-six of the patients had abnormal TDD (sensitivity 0.60) and 20 had abnormal vibration detection (sensitivity 0.46). Ten of the patients had abnormal TDD and normal vibration detection. Four of the patients had abnormal vibration detection and normal TDD. Test-retest examination of TDD showed a high degree of reproducibility (r = 0.87). TDD seems more useful than vibration detection in examination of diabetic neuropathy.

  6. 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.

  7. Amitriptyline and Sertraline in Diabetic Neuropathy: A Comparative ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of amitriptyline (Ami) and sertraline (Sert) in diabetes neuropathy. Methods: Diabetes was induced in 3 groups of rats (n=6) with streptozotocin (STZ, 55mg/kg, i.p.). Two of the groups of diabetic rats received amitriptyline (15 mg/kg, p.o) and sertraline (30 mg/kg, p.o.) while another 2 groups ...

  8. 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

    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....

  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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy.

    Science.gov (United States)

    Kaur, Navpreet; Kishore, Lalit; Singh, Randhir

    2017-07-12

    According to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy. The aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes. Diabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species. significantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats. Thus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

    Science.gov (United States)

    Javed, Saad; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. PMID:26676662

  12. 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

    2017-05-01

    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 (pneuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. 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.

  14. The identification of gene expression profiles associated with progression of human diabetic neuropathy

    Science.gov (United States)

    Hur, Junguk; Sullivan, Kelli A.; Pande, Manjusha; Hong, Yu; Sima, Anders A. F.; Jagadish, Hosagrahar V.; Kretzler, Matthias

    2011-01-01

    Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies. PMID:21926103

  15. 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....

  16. Is calprotectin a novel biomarker of neuroinflammation in diabetic periferal neuropathy?

    Science.gov (United States)

    Tabur, Suzan; Korkmaz, Hakan; Ozkaya, Mesut; Aksoy, Sefika Nur; Akarsu, Ersin

    2015-01-01

    In the present study, we aimed to investigate serum calprotectin levels in patients with diabetic peripheral neuropathy, and possible role of this molecule in the disease pathogenesis. Twenty nine patients with diabetic peripheral neuropathy, 30 type 2 diabetic patients without neuropathy, and 40 healthy controls were enrolled in the study. Fasting plasma glucose (FPG), high-density lipoprotein- cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), total cholesterol, triglyceride, HbA1c, calprotectin and hsCRP levels were measured in diabetic and healthy control groups. Serum calprotectin and hsCRP levels were significantly higher in patients with and without neuropathy than healthy controls (p diabetics with neuropathy than the ones without (p = 0.021 and p neuropathy development and hsCRP and serum calprotectin levels in diabetic individuals. Seum calprotectin levels were increased in diabetic peripheral neuropathy. It may have a role in the pathogenesis of the disease.

  17. Electrophysiological changes in sensorimotor nerves in diabetes mellitus & usefulness of nerve conduction studies for early diagnosis of diabetic neuropathy

    OpenAIRE

    Pandya, Dr. Neha Harjivanbhai; Desai, Dr. Kinnar Somabhai; Goswami, Dr. Toral; Patel, Dr. Vaishali; Mevada, Dr. Amita; Suthar, Dr. Mitesh

    2013-01-01

    Background: Diabetes Mellitus(DM) a metabolic disorder is the most common cause of peripheral neuropathy. As a result of long term hyperglycemia there is damage to nerves that develops diabetic neuropathy. Nerve conduction studies(NCS) are commonly employed to detect the neuropathy. The present study was undertaken to find out the utility of NCS as an early indicator of neuropathy in diabetic patients.Materials & methods: Study was carried out in 50 diagnosed DM patients attending outpati...

  18. 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

  19. 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...

  20. 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 respons...

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

    Directory of Open Access Journals (Sweden)

    Jia-Ying Sung

    Full Text Available 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.

  2. Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

    Science.gov (United States)

    Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

    2015-01-01

    Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

  3. Hip joint torques in type II diabetes with and without neuropathy

    Directory of Open Access Journals (Sweden)

    Laleh Abadi, MS (PT

    2017-12-01

    Full Text Available Background: Patients with diabetes and peripheral neuropathy demonstrate significantly reduced peak torques at the peripheral joints. Objectives: The aim of this study was to assess isometric and concentric peak torques of the hip joint in people with type II diabetes with and without peripheral neuropathy in comparison with healthy participants. Methods: 27 patients with type II diabetes including 15 patients without peripheral neuropathy, 12 patients with diabetes and peripheral neuropathy and 15 healthy people participated. Isometric and concentric peak torques of hip flexion, extension, adduction and abduction of the non-dominant leg were measured by motorized dynamometer. Results: Peak and average peak concentric torques of the hip extension and abduction in patients with diabetes and peripheral neuropathy were lower than those patients with diabetes and control group. Angle of extension peak torque was significantly greater in patients with diabetes and peripheral neuropathy compared with other groups. Angle of flexion peak torque was lower in the patients with diabetes and peripheral neuropathy. Conclusions: Torque related parameters in patients with type II diabetes with or without peripheral neuropathy, are different from healthy subjects. As a result, patients with diabetes especially with peripheral neuropathy are more susceptible of injury and disability in lower limbs. Keywords: type II diabetes, hip, joint, torques, peripheral neuropathy

  4. [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.

  5. Regional anesthesia in diabetic peripheral neuropathy

    NARCIS (Netherlands)

    ten Hoope, Werner; Looije, Marjolein; Lirk, Philipp

    2017-01-01

    The aim of this review is to summarize recent relevant literature regarding regional anesthesia in the diabetic neuropathic patient and formulate recommendations for clinical practice. Diabetic neuropathic nerves, but not nerves of diabetic patients per se, exhibit complex functional changes. As a

  6. Diabetic Driving Studies-Part 2: A Comparison of Brake Response Time Between Drivers With Diabetes With and Without Lower Extremity Sensorimotor Neuropathy.

    Science.gov (United States)

    Spiess, Kerianne E; Sansosti, Laura E; Meyr, Andrew J

    We have previously demonstrated an abnormally delayed mean brake response time and an increased frequency of abnormally delayed brake responses in a group of neuropathic drivers with diabetes compared with a control group of drivers with neither diabetes nor lower extremity neuropathy. The objective of the present case-control study was to compare the mean brake response time between 2 groups of drivers with diabetes with and without lower extremity sensorimotor neuropathy. The braking performances of the participants were evaluated using a computerized driving simulator with specific measurement of the mean brake response time and the frequency of the abnormally delayed brake responses. We compared a control group of 25 active drivers with type 2 diabetes without lower extremity neuropathy and an experimental group of 25 active drivers with type 2 diabetes and lower extremity neuropathy from an urban U.S. podiatric medical clinic. The experimental group demonstrated an 11.49% slower mean brake response time (0.757 ± 0.180 versus 0.679 ± 0.120 second; p diabetic drivers with neuropathy demonstrated a mean brake response time slower than a suggested safety threshold of 0.70 second, and diabetic drivers without neuropathy demonstrated a mean brake response time faster than this threshold. The results of the present investigation provide evidence that the specific onset of lower extremity sensorimotor neuropathy associated with diabetes appears to impart a negative effect on automobile brake responses. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Effect of Kaempferol isolated from seeds of Eruca sativa on changes of pain sensitivity in Streptozotocin-induced diabetic neuropathy.

    Science.gov (United States)

    Kishore, Lalit; Kaur, Navpreet; Singh, Randhir

    2017-11-20

    Generation of excessive reactive oxygen species (ROS) and advanced glycation end products (AGEs), and cellular apoptosis are implicated in the pathogenesis of diabetic neuropathy. Present study was aimed to explore the effect of Eruca sativa and Kaempferol (KP) on hyperalgesia (thermal and mechanical); tactile allodynia, motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin (STZ) induced experimental diabetes. Neuropathy developed in diabetic rats was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with excess formation of AGEs and ROS. Chronic treatment with E. sativa hydroalcoholic extract (EHA; 100, 200 and 400 mg/kg) and KP (5 and 10 mg/kg) for 30 days starting from the 60th day of STZ administration significantly ameliorated behavioral and biochemical changes linked to diabetic neuropathy. Present study suggested that EHA and KP corrected hyperglycemia and reversed the pain response partially in diabetic rats along via modulating oxidative and nitrosative stress along with reduction of AGEs formation in diabetic rats. Thus E. sativa might be beneficial in chronic diabetes, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

  8. 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...

  9. Rocker outsole shoe is not a threat to postural stability in patients with diabetic neuropathy.

    Science.gov (United States)

    Ghomian, Banafshe; Kamyab, Mojtaba; Jafari, Hassan; Khamseh, Mohammadebrahim; Healy, Aoife

    2016-04-01

    Rocker outsole shoes are commonly prescribed to patients with diabetic neuropathy to offload a particular area of the foot sole, thereby decreasing the risk of foot ulceration. Contrary to this, some evidence has reported a postural destabilising effect of these shoes in healthy adults. To explore the postural stability of patients with diabetic neuropathy who wear a rocker outsole shoe. Quasi-experimental. In total, 17 patients with diabetic neuropathy (aged 49.29 ± 7.48 years; 7 female, 10 males) participated in this study. A Motor Control Test measuring centre of force displacement, response strength scale and response latency in medium and large perturbations was conducted using the EquiTest system to evaluate postural stability while wearing a baseline shoe (without a rocker outsole) or a rocker outsole shoe (with a toe-only rocker sole). No significant difference was observed between the shoe conditions in centre of force displacement and response latency of the participants (p > 0.05). The results indicated a significant increase in the response strength scale of participants by the rocker outsole, for medium forward and backward and large forward perturbations (p = 0.014, p = 0.001 and p = 0.027, respectively). When the immediate effect is a concern, the rocker outsole shoe did not negatively affect postural stability in patients with diabetic neuropathy. This article will provide objective evidence about the effect of rocker outsole on postural balance in diabetic patients. In prescription of rocker outsole to prevent plantar ulceration of diabetic foot, immediate postural destabilising is not a concern. © The International Society for Prosthetics and Orthotics 2014.

  10. 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. 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...

  12. Association of Diabetic Neuropathy with Duration of Type 2 Diabetes and Glycemic Control.

    Science.gov (United States)

    Nisar, Muhammad Umer; Asad, Ambreen; Waqas, Ahmed; Ali, Nazia; Nisar, Anam; Qayyum, Mohsin A; Maryam, Hafsa; Javaid, Mohsin; Jamil, Mohsin

    2015-08-12

    Diabetes mellitus is associated with severe microvascular and macrovascular complications with major implications for public health. Diabetic neuropathy is a very problematic complication of diabetes mellitus. It is associated with severe morbidity, mortality, and a huge economic burden. The present study was designed with two aims: 1) to analyze the association of diabetic neuropathy with the glycemic index (levels of fasting blood glucose, random blood glucose, and Hb1Ac) in patients with Type 2 diabetes, and 2) to analyze the association of diabetic neuropathy with time passed since the diagnosis of diabetes. This case-control study was undertaken between June 2013 and February 2015 in the Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi, Pakistan. Type 2 diabetics with an age range of 30-60 years were recruited from outpatient departments of AFIRM, Rawalpindi. Data were collected and recorded on a form with four sections recording the following: 1) demographics of patients and number of years passed since diagnosis of diabetes; 2) clinical examination for touch, pressure, power, pain, vibration, and ankle reflex; 3) nerve conduction studies for motor components of the common peroneal nerve and tibial nerve and the sensory component of median nerve and sural nerve; 4) glycemic index, including fasting blood glucose levels (BSF), random blood glucose (BSR) levels, and HbA1c levels. Data were analyzed in SPSS v. 20. Chi-square and phi statistics and logistic regression analysis were run to analyze associations between diabetic neuropathy and time passed since diagnosis of diabetes and glycemic index. In total, 152 patients were recruited. One-half of those patients had neuropathy (76 patients) and the other half (76 patients) had normal nerve function. The mean (standard deviation [SD]) duration of diabetes was nine years (6.76), BSF levels 7.98 mmol/l (2.18), BSR 9.5 mmol/l (3.19), and HbA1c 6.5% (2.18). Logistic regression analysis

  13. Radiographic Abnormalities in the Feet of Diabetic Patients with Neuropathy and Foot Ulceration.

    Science.gov (United States)

    Viswanathan, Vijay; Kumpatla, Satyavani; Rao, V Narayan

    2014-11-01

    People with diabetic neuropathy are frequently prone to several bone and joint abnormalities. Simple radiographic findings have been proven to be quite useful in the detection of such abnormalities, which might be helpful not only for early diagnosis but also in following the course of diabetes through stages of reconstruction of the ulcerated foot.The present study was designed to identify the common foot abnormalities in south Indian diabetic subjects with and without neuropathy using radiographic imaging. About 150 (M:F 94:56) subjects with type 2 diabetes were categorised into three groups: Group I (50 diabetic patients), Group II (50 patients with neuropathy), and Group III (50 diabetic patients with both neuropathy and foot ulceration). Demographic details, duration of diabetes and HbA1c values were recorded. Vibration perception threshold was measured for assessment of neuropathy. Bone and joint abnormalities in the feet and legs of the study subjects were identified using standardised dorsi-plantar and lateral weight-bearing radiographs. Radiographic findings of the study subjects revealed that those with both neuropathy and foot ulceration and a longer duration of diabetes had more number of bone and joint abnormalities. Subjects with neuropathy alone also showed presence of several abnormalities, including periosteal reaction, osteopenia, and Charcot changes. The present findings highlight the impact of neuropathy and duration of diabetes on the development of foot abnormalities in subjects with diabetes. Using radiographic imaging can help in early identification of abnormalities and better management of the diabetic foot.

  14. Benfotiamine and Alpha-Lipoic Acid in the Treatment of Diabetic Cardiovascular Autonomic Neuropathy (Review of Literature and Own Researches

    Directory of Open Access Journals (Sweden)

    V.O. Sergiyenko

    2014-06-01

    Full Text Available The analysis of current views on the mechanisms of fat-soluble form of vitamin B1 (benfotiamine and α-lipoic acid action, in particular features of their impact on carbohydrate and lipid metabolism, endothelial function, hemodynamics, vessel stiffness in cardiovascular diseases, cardiovascular autonomic neuropathy in type 2 diabetes mellitus, was perfomed. The results of experimental, randomized and own studies confirmed the value of the combined administration of benfotiamine and α-lipoic acid for the prevention and treatment of cardiovascular diseases, in particular cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

  15. Quality of Life in Patients with Diabetes Mellitus Type 2 with Metabolic Neuropathy against Pathogenic Therapy

    Directory of Open Access Journals (Sweden)

    M.V. Vlasenko

    2013-01-01

    Full Text Available The article deals with one of the most important and urgent problems of endocrinology — diabetes mellitus and its most common and difficult-to-treat complication — diabetic neuropathy. Clinical picture and diagnostic issues of this disease are described in detail, major principles of the treatment of patients with diabetic neuropathy as recommended by the American Diabetes Association and the European Association for the Study of Diabetes (2012 are demonstrated.

  16. Retinal sensitivity changes associated with diabetic neuropathy in the absence of diabetic retinopathy.

    Science.gov (United States)

    Neriyanuri, Srividya; Pardhan, Shahina; Gella, Laxmi; Pal, Sakshyar Saumya; Ganesan, Suganeswari; Sharma, Tarun; Raman, Rajiv

    2017-09-01

    To explore any relationship between the markers of early retinal neuronal damage and peripheral diabetic neuropathy in subjects with no diabetic retinopathy (DR). A cross-sectional study in which type 2 diabetic subjects (n=743) without DR were studied. Visual functions including visual acuity, contrast sensitivity, colour vision, retinal sensitivity using microperimeter and retinal thicknesses by spectral domain optical coherence tomography were measured. Vibration perception thresholds of greater than or equal to 20 µV, measured by sensitometer using a biothesiometer probe, were defined as having peripheral diabetic neuropathy. Statistical analyses were performed using independent t-test, multivariate logistic regression and Pearson's correlation. Of 743 subjects who had no DR, 24.9% had diabetic neuropathy. Independent comparisons among subjects who had diabetic neuropathy compared with those who did not showed statistically significant retinal nerve fibre layer thinning (p=0.01), reduced contrast sensitivity (p=0.0001), reduced retinal sensitivity (p=0.03), impaired colour vision (p=0.04) and reduced visual acuity (p=0.0001). Multivariate analysis showed significant association between the mean retinal sensitivity (measured using a microperimeter) and diabetic neuropathy (adjusted OR (95% CI): 0.76 (0.60 to 0.95), p=0.01). Significant association of neuroretinal dysfunction with the presence of diabetic neuropathy was noted among subjects with no DR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. 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.

  18. 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....

  19. 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.

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

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    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.

  1. 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 di...

  2. Cardiovascular autonomic neuropathy in patients with diabetes mellitus.

    Science.gov (United States)

    Lozano, T; Ena, J

    Cardiovascular autonomic neuropathy associated with diabetes mellitus is caused by an impairment of the autonomic system. The prevalence of this condition ranges from 20% to 65%, depending on the duration of the diabetes mellitus. Clinically, the autonomic function disorder is associated with resting tachycardia, exercise intolerance, orthostatic hypotension, intraoperative cardiovascular instability, silent myocardial ischemia and increased mortality. For the diagnosis, the integrity of the parasympathetic and sympathetic nervous system is assessed. Parasympathetic activity is examined by measuring heart rate variability in response to deep breathing, standing and the Valsalva manoeuvre. Sympathetic integrity is examined by measuring blood pressure in response to standing and isometric exercise. The treatment includes the metabolic control of diabetes mellitus and of the cardiovascular risk factors. Treating symptoms such as orthostatic hypotension requires special attention. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  3. Cardiovascular autonomic neuropathy in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    May, O.; Arildsen, H.; Damsgaard, E.M.

    2000-01-01

    OBJECTIVES: The aim of the study was to estimate the prevalence of cardiovascular autonomic neuropathy (CAN) in Type 1 diabetes mellitus in the general population and to assess the relationship between CAN and risk of future coronary heart disease (CHD). METHODS: The Type 1 diabetes mellitus...... = 0.001). Exercise capacity, rise in systolic blood pressure and heart rate were positively correlated with the E/I ratio. A high VA Prognostic Score was correlated with a low E/I ratio (r = - 0.58, P ...%. The E/I ratio was significantly reduced in old age, long duration of diabetes, female gender, high fasting blood glucose, triglyceride, systolic blood pressure and urinary albumin excretion. A high risk of future CHD calculated using the Framingham model was associated with a low E/I ratio (r = -0.39, P...

  4. High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

    Science.gov (United States)

    Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

    2017-12-01

    High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm2) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score (p diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm2) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

  5. High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Kunwarpal Singh

    2017-12-01

    Full Text Available Aim of the study: High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. Material and methods: 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. Results: The mean cross sectional area (22.63 +/– 2.66 mm2 and maximum thickness of nerve fascicles (0.70 mm of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score (p < 0.001. The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/– 1.72 mm2 and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm than healthy non-diabetic subjects (12.42 +/– 1.01 mm2 and 0.30 mm respectively. Conclusion: The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

  6. Cough reflex sensitivity in adolescents with diabetic autonomic neuropathy

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    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.

  7. 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.

  8. Agreement between automated and manual quantification of corneal nerve fiber length: Implications for diabetic neuropathy research.

    Science.gov (United States)

    Scarr, Daniel; Lovblom, Leif E; Ostrovski, Ilia; Kelly, Dylan; Wu, Tong; Farooqi, Mohammed A; Halpern, Elise M; Ngo, Mylan; Ng, Eduardo; Orszag, Andrej; Bril, Vera; Perkins, Bruce A

    2017-06-01

    Quantification of corneal nerve fiber length (CNFL) by in vivo corneal confocal microscopy represents a promising diabetic neuropathy biomarker, but applicability is limited by resource-intensive image analysis. We aimed to evaluate, in cross-sectional analysis of non-diabetic controls and patients with type 1 and type 2 diabetes with and without neuropathy, the agreement between manual and automated analysis protocols. Sixty-eight controls, 139 type 1 diabetes, and 249 type 2 diabetes participants underwent CNFL measurement (N=456). Neuropathy status was determined by clinical and electrophysiological criteria. CNFL was determined by manual (CNFLManual, reference standard) and automated (CNFLAuto) protocols, and results were compared for correlation and agreement using Spearman coefficients and the method of Bland and Altman (CNFLManual subtracted from CNFLAuto). Participants demonstrated broad variability in clinical characteristics associated with neuropathy. The mean age, diabetes duration, and HbA1c were 53±18years, 15.9±12.6years, and 7.4±1.7%, respectively, and 218 (56%) individuals with diabetes had neuropathy. Mean CNFLManual was 15.1±4.9mm/mm2, and mean CNFLAuto was 10.5±3.7mm/mm2 (CNFLAuto underestimation bias, -4.6±2.6mm/mm2 corresponding to -29±17%). Percent bias was similar across non-diabetic controls (-33±12%), type 1 (-30±20%), and type 2 diabetes (-28±16%) subgroups (ANOVA, p=0.068), and similarly in diabetes participants with and without neuropathy. Levels of CNFLAuto and CNFLManual were both inversely associated with neuropathy status. Although CNFLAuto substantially underestimated CNFLManual, its bias was non-differential between diverse patient groups and its relationship with neuropathy status was preserved. Determination of diagnostic thresholds specific to CNFLAuto should be pursued in diagnostic studies of diabetic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Diabetic neuropathy examination - A hierarchical scoring system to diagnose distal polyneuropathy in diabetes

    NARCIS (Netherlands)

    Meijer, JWG; van Sonderen, E; Blaauwwiekel, EE; Smit, AJ; Groothoff, JW; Eisma, WH; Links, TP

    OBJECTIVE - Existing physical examination scoring systems for distal diabetic polyneuropathy (PNP) do not fulfill all of the following criteria: validity, manageability, predictive value, and hierarchy. The aim of this study was to adapt the Neuropathy Disability Score (NDS) to diagnose PNP in

  10. 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.

  11. Effect of Atibalamula and Bhumyamalaki on thirty-three patients of diabetic neuropathy

    OpenAIRE

    Patel, Kalapi; Patel, Manish; Gupta, S N

    2011-01-01

    Diabetic neuropathy is a relatively early and common complication affecting approximately 30% of diabetic patients. According to Ayurvedic principles there is involvement of Vata and Pitta Dosa in diabetic neuropathy. Bhumyamalaki (Phyllanthus niruri) is a plant which shows possibility to pacify these two Dosas. Another plant Atibala (Abutilon indicum) has also Vata pacifying qualities. Present study has been carried out to study the effects of Bhumyamalaki and Atibala on 33 patients of diabe...

  12. Hyperbaric oxygen therapy of olfactory dysfunction in diabetic neuropathy with type 2 diabetes mellitus and a new definition Diabetic Olfactopathy.

    Science.gov (United States)

    Veyseller, B; Dogan, R; Yenigun, A; Aksoy, F; Tugrul, S; Dogan, E E; Ozturan, O

    2016-05-12

    Hyperbaric Oxygen therapy is recommended as an adjuvant therapy for diabetic neuropathy. To investigate olfactory dysfunction and show the effectiveness of hyperbaric oxygen treatment in patients with type 2 diabetic neuropathy. Patients diagnosed with Type 2 DM and diabetic neuropathy were included in the group 1. Patients of Group 1 were administered with a hyperbaric oxygen therapy for 30 sessions and patients who returned for a check up following 30 sessions were incorporated into the Group 2. Healthy volunteers with no medical problems were included in the study as a control group (Group 3). Connecticut Chemosensory Clinical Research (CCCRC) test and the subjective visual analog scale (VAS; 0-100) were utilized to evaluate the olfactory function. There was a statistically significant difference both between the control group and the patient group as well as before and after the HBO therapy in terms of total CCCRC scoring averages and VAS Scoring averages. When compared to normal individuals, type 2 diabetic neuropathy can cause an olfactory dysfunction, and a statistically significant improvement in olfaction can be obtained with HBO therapy. This is the first study demonstrating that the HBO therapy can play a role in treating olfactory dysfunctions suffered by the patients with diabetic olfactory neuropathies.

  13. 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.

  14. Diurnal body temperature rise is reduced in diabetes with autonomic neuropathy.

    Science.gov (United States)

    Amiya, Eisuke; Watanabe, Masafumi; Takata, Munenori; Nakao, Tomoko; Hosoya, Yumiko; Watanabe, Shogo; Nagai, Ryozo; Komuro, Issei

    2014-04-01

    We conducted a retrospective study of 60 patients with ischemic heart disease (31 with diabetes and 29 without diabetes) to investigate the impact of diabetes on diurnal body temperature patterns. We found that the increase of axillary body temperature in the evening was reduced in the presence of diabetes, which was associated with autonomic neuropathy.

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

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    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.

  16. 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.

  17. Identification of genes and signaling pathways associated with diabetic neuropathy using a weighted correlation network analysis

    Science.gov (United States)

    Li, Ya; Ma, Weiguo; Xie, Chuanqing; Zhang, Min; Yin, Xiaohong; Wang, Fenfen; Xu, Jie; Shi, Bingyin

    2016-01-01

    Abstract Background: The molecular mechanisms behind diabetic neuropathy remains to be investigated. Methods: This is a secondary study on microarray dataset (GSE24290) downloaded from Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI), which included 18 nerve tissue samples of progressing diabetic neuropathy (fibers loss ≥500 fibers/mm2) and 17 nerve tissue samples of nonprogressing diabetic neuropathy (fibers loss ≤100 fibers/mm2). Differentially expressed genes (DEGs) were screened between progressing and nonprogressing diabetic neuropathy. With the DEGs obtained, a weighted gene coexpression network analysis was conducted to identify gene clusters associated with diabetic neuropathy. Diabetes-related microRNAs (miRNAs) and their target genes were predicted and mapped to the genes in the gene clusters identified. Consequently, a miRNA–gene network was constructed, for which gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Potential drugs for treatment of diabetic neuropathy were also predicted. Results: Total 370 upregulated and 379 downregulated DEGs were screened between nonprogressing and progressing diabetic neuropathy. Has-miR-377, has-miR-216a, and has-miR-217 were associated with diabetes. Inflammation was the most significant GO term. The peroxisome proliferator-activated receptor (PPAR) pathway and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway were significantly KEGG pathways significantly enriched with PPAR gamma (PPARG), stearoyl-CoA desaturase (SCD), cluster of differentiation 36 (CD36), and phosphoenolpyruvate carboxykinase 1 (PCK1). Conclusion: The study suggests that PPARG, SCD, CD36, PCK1, AMPK pathway, and PPAR pathway may be involved in progression of diabetic neuropathy. PMID:27893688

  18. mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy.

    Science.gov (United States)

    Chandrasekaran, Krish; Muragundla, Anjaneyulu; Demarest, Tyler G; Choi, Joungil; Sagi, Avinash R; Najimi, Neda; Kumar, Pranith; Singh, Anmol; Ho, Cheng-Ying; Fiskum, Gary; Koch, Lauren G; Britton, Steven L; Russell, James W

    2017-12-01

    There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function. Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268. Neuropathy end points included mechanical allodynia, nerve conduction velocities (NCV), and intraepidermal nerve fiber density (IENFD). Markers of oxidative stress, antioxidant response, glutamate recycling pathways, and mitochondrial oxidative phosphorylation (OXPHOS) associated proteins were measured in dorsal root ganglia (DRG). In diabetic rats, NCV and IENFD were decreased. Diabetic rats treated with an mGluR2/3 agonist did not develop neuropathy despite remaining diabetic. Diabetic DRG showed increased levels of oxidized proteins, decreased levels of glutathione, decreased levels of mitochondrial DNA (mtDNA) and OXPHOS proteins. In addition, there was a 20-fold increase in levels of glial fibrillary acidic protein (GFAP) and the levels of glutamine synthetase and glutamate transporter proteins were decreased. When treated with a specific mGluR2/3 agonist, levels of glutathione, GFAP and oxidized proteins were normalized and levels of superoxide dismutase 2 (SOD2), SIRT1, PGC-1α, TFAM, glutamate transporter proteins, and glutamine synthetase were increased in DRG neurons. Activation of glutamate recycling pathways protects diabetic DRG and this is associated with activation of the SIRT1-PGC-1α-TFAM axis and preservation of mitochondrial OXPHOS function.

  19. 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.)

  20. The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals.

    Science.gov (United States)

    Ferreira, Jean P; Sartor, Cristina D; Leal, Ângela M O; Sacco, Isabel C N; Sato, Tatiana O; Ribeiro, Ivana L; Soares, Alice S; Cunha, Jonathan E; Salvini, Tania F

    2017-03-01

    Skeletal muscle strength is poorly described and understood in diabetic participants with diabetic peripheral neuropathy. This study aimed to investigate the extensor and flexor torque of the knee and ankle during concentric, eccentric, and isometric contractions in men with diabetes mellitus type 2 with and without diabetic peripheral neuropathy. Three groups of adult men (n=92), similar in age, body mass index, and testosterone levels, were analyzed: 33 non-diabetic controls, 31 with type 2 diabetes mellitus, and 28 with diabetic peripheral neuropathy. The peak torques in the concentric, eccentric, and isometric contractions were evaluated using an isokinetic dynamometer during knee and ankle flexion and extension. Individuals with diabetes and diabetic peripheral neuropathy presented similar low concentric and isometric knee and ankle torques that were also lower than the controls. However, the eccentric torque was similar among the groups, the contractions, and the joints. Regardless of the presence of peripheral neuropathy, differences in skeletal muscle function were found. The muscle involvement does not follow the same pattern of sensorial losses, since there are no distal-to-proximal impairments. Both knee and ankle were affected, but the effect sizes of the concentric and isometric torques were found to be greater in the participants' knees than in their ankles. The eccentric function did not reveal differences between the healthy control group and the two diabetic groups, raising questions about the involvement of the passive muscle components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

    Science.gov (United States)

    Farmer, Kevin L.; Li, Chengyuan

    2012-01-01

    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. PMID:22885705

  2. Recognition and management of psychosocial issues in diabetic neuropathy.

    Science.gov (United States)

    Vileikyte, Loretta; Gonzalez, Jeffrey S

    2014-01-01

    Although psychosocial aspects of diabetic neuropathy (DN) have received far less attention than biological aspects, research conducted over the last decade has begun to illuminate several important pathways between DN and psychosocial outcomes, including depression, anxiety, and self-management of diabetic foot ulcer (DFU)-risk. Growing body of evidence indicates that DN is a risk factor for depression predicting both the severity and increments in depression over time. Whereas painful DN contributes to depression, postural instability is the DN symptom with the strongest, cumulative effect on depression. Furthermore, depression and foot self-care, while having no impact on the development of recurrent diabetic foot ulcers (DFU), play a substantial role in incident first DFU. Patient common sense misconceptions about DFU risks and associated emotional responses play an important role in shaping foot self-care. Depression, and especially DFU-specific emotions, may be linked to DFU chronicity through biological and behavioral pathways that are at present under investigation in several ongoing trials. Integrative approaches that target psychological factors such as anxiety and depression while concurrently optimizing treatment and self-management may therefore be most powerful. Cognitive behavioral therapy-based techniques that are informed by these findings deserve investigation.

  3. Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

    NARCIS (Netherlands)

    Lirk, P.; Verhamme, C.; Boeckh, R.; Stevens, M. F.; ten Hoope, W.; Gerner, P.; Blumenthal, S.; de Girolami, U.; van Schaik, I. N.; Hollmann, M. W.; Picardi, S.

    2015-01-01

    The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control

  4. In Zucker Diabetic Fatty Rats, Subclinical Diabetic Neuropathy Increases In Vivo Lidocaine Block Duration But Not In Vitro Neurotoxicity

    NARCIS (Netherlands)

    Lirk, Philipp; Flatz, Magdalena; Haller, Ingrid; Hausott, Barbara; Blumenthal, Stephan; Stevens, Markus F.; Suzuki, Suzuko; Klimaschewski, Lars; Gerner, Peter

    2012-01-01

    Background and Objectives: Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. In addition, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity

  5. Cardiovascular Autonomic Neuropathy and Early Atherosclerosis in Adolescent Type 1 Diabetic Patient

    Directory of Open Access Journals (Sweden)

    Soha M. Abd El Dayem

    2015-12-01

    CONCLUSION: Percentage of arrhythmia and early atherosclerosis is high in adolescent type 1 diabetic patients. CAN is associated with early atherosclerosis. Cardiac autonomic neuropathy is associated with older age, longer duration, and poor glycemic control and microalbuminuria.

  6. Safety of aerobic exercise in people with diabetic peripheral neuropathy: single-group clinical trial

    National Research Council Canada - National Science Library

    Kluding, Patricia M; Pasnoor, Mamatha; Singh, Rupali; D'Silva, Linda J; Yoo, Min; Billinger, Sandra A; LeMaster, Joseph W; Dimachkie, Mazen M; Herbelin, Laura; Wright, Douglas E

    2015-01-01

    .... This was a single-group preliminary study. The setting was an academic medical center. Participants were 18 people who were sedentary and had type 2 diabetes and peripheral neuropathy (mean age=58.1 years, SD=5...

  7. Standardizing corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy.

    Science.gov (United States)

    Edwards, K; Pritchard, N; Vagenas, D; Russell, A; Malik, R A; Efron, N

    2014-10-01

    Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm², P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. Standardizing corneal nerve fibre length for

  8. Morphofunctional characteristics of the foot in patients with diabetes mellitus and diabetic neuropathy.

    Science.gov (United States)

    García-Álvarez, Yolanda; Lázaro-Martínez, José Luis; García-Morales, Esther; Cecilia-Matilla, Almudena; Aragón-Sánchez, Javier; Carabantes-Alarcón, David

    2013-01-01

    To determine the structural and biomechanical characteristics associated with the conditions diabetes mellitus and diabetic neuropathy. Observational study of 788 patients conducted between February 2007 and February 2009, which included subjects with and without diabetes mellitus who had no active ulcer at enrollment. Demographic variables and the general and specific history of diabetes mellitus were recorded. The patient's foot type according to the Foot Posture Index, joint mobility and deformity were recorded. No associations were found between the different foot types (neutral, pronated and supinated) and the structural and demographic variables at a general level, except for the pronated foot that was associated with a higher body mass index, longer suffering from diabetes and the presence of neuropathy [pdiabetes and limited joint mobility in patients with diabetes mellitus and pronated foot may be a high-risk anthropometric pattern for developing associated complications such as Charcot foot. A prospective analysis of these patients is required to define the risk for developing Charcot neuroarthropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  9. Relationship of planter pressure and glycemic control in type 2 diabetic patients with and without neuropathy.

    Science.gov (United States)

    Halawa, Mohammed R; Eid, Yara M; El-Hilaly, Rana A; Abdelsalam, Mona M; Amer, Amr H

    2017-09-23

    Foot disease is a common complication of type 2 diabetes that can have tragic consequences. Abnormal plantar pressures are considered to play a major role in the pathologies of neuropathic ulcers in the diabetic foot. To examine Relationship of Planter Pressure and Glycemic Control in Type 2 Diabetic Patients with and without Neuropathy. The study was conducted on 50 type 2 diabetic patients and 30 healthy volunteers. BMI calculation, disease duration, Hemoglobin A1c and presence of neuropathy (by history, foot examination and DN4 questionnaire) were recorded. Plantar pressure was recorded for all patients using the Mat-scan (Tekscan, Inc.vers. 6.34 Boston USA) in static conditions (standing) and dynamic conditions (taking a step on the Mat-scan). Plantar pressures (kPa) were determined at the five metatarsal areas, mid foot area, medial and lateral heel areas and medial three toes. Static and dynamic plantar pressures in both right and left feet were significantly higher in diabetic with neuropathy group than in control group in measured areas (Pdiabetic with neuropathy group than in diabetic without neuropathy group in measured areas (Pdiabetic without neuropathy group there was a significant difference in plantar pressures especially in metatarsal areas (Pdiabetic neuropathy have elevated peak plantar pressure (PPP) compared to patients without neuropathy and control group. HbA1c% as a surrogate for glycemic control had no direct impact on peak planter pressure, yet it indirectly impacts neuropathy evolution through out disease duration eventually leading to the drastic planter pressure and gait biomechanics changes. Copyright © 2017. Published by Elsevier Ltd.

  10. 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....

  11. Relationships Between Type 2 Diabetes, Neuropathy, and Microvascular Dysfunction : Evidence From Patients With Cryptogenic Axonal Polyneuropathy

    NARCIS (Netherlands)

    Emanuel, Anna L; Nieuwenhoff, Mariska D; Klaassen, Erica S; Verma, Ajay; Kramer, Mark H H; Strijers, Rob; Vrancken, Alexander F J E; Eringa, Etto; Groeneveld, Geert Jan; Serné, Erik H

    OBJECTIVE: This study investigated whether the relationship between neuropathy and microvascular dysfunction in patients with type 2 diabetes is independent of diabetes-related factors. For this purpose, we compared skin microvascular function in patients with type 2 diabetes with that of patients

  12. Ambulatory screening of diabetic neuropathy and predictors of its severity in outpatient settings.

    Science.gov (United States)

    Qureshi, M S; Iqbal, M; Zahoor, S; Ali, J; Javed, M U

    2017-04-01

    Diabetic neuropathy is one of the most common causes of chronic neuropathic symptomatology and the most disabling and difficult-to-treat diabetic microangiopathic complication. The neuropathies associated with diabetes are typically classified into generalized, focal and multifocal varieties. There exists a scarcity of literature studying the correlation of different patient- and disease-related variables with severity of neuropathy. This study aims to delineate the prevalence of diabetic neuropathy in type 2 diabetes, describe its characteristics and find out predictors of its severity. Eight hundred consecutive diabetic patients presenting to outpatient department (OPD) of Khan Research Labs (KRL) General Hospital and Centre for Diabetes and Liver diseases, Islamabad, during March-June, 2015 were made to complete a self-administered questionnaire (Michigan Neuropathy Screening Instrument-MNSI) and underwent a thorough physical examination according to MNSI protocols. A score of >2 was considered to be diagnostic for DPN. Patient and disease variables were noted. MNSI score was used as an index of severity of diabetic peripheral neuropathy (DPN). Correlation of several patient- and disease-related variables with the severity of DPN was determined using multivariate regression. Out of a total 800 patients screened, 90 (11.25%) were found to have diabetic neuropathy. Of these 90, 45.5% were males, the median age was 54.47 ± 10.87 years and the median duration of diabetes was 11.12 ± 9.8 years. The most common symptom was found to be numbness (63.6%) followed by generalized body weakness (61.5%). The common findings on physical examination were dry skin/callus (38.7%) and deformities (14.7%). Duration of diabetes was found to be the strongest predictor for development and severity of diabetic neuropathy followed by glycemic controls (HbA1c values) and age. Duration of diabetes rather than diabetic controls predicts better the development and severity of

  13. Diabetic Neuropathy: Update on Pathophysiological Mechanism and the Possible Involvement of Glutamate Pathways.

    Science.gov (United States)

    Hussain, Nadia; Adrian, Thomas E

    2017-01-01

    Diabetic neuropathy is a common complication of diabetes. It adversely affects the lives of most diabetics. It is the leading cause of non-traumatic limb amputation. Diabetic autonomic neuropathy can target any system and increases morbidity and mortality. Treatment begins with adequate glycemic control but despite this, many patients go on to develop neuropathy which suggests there are additional and unidentified, as yet, pathological mechanisms in place. Although several theories exist, the exact mechanisms are not yet established. Disease modifying treatment requires a more complete understanding of the mechanisms of disease. Pathways Involved: This review discusses the potential pathological mechanisms of diabetic neuropathy, including the polyol pathway, hexosamine pathway, protein kinase C, advanced glycation end product formation, polyADP ribose polymerase, and the role of oxidative stress, inflammation, growth factors and lipid abnormalities. Finally it focuses on how possible changes in glutamate signaling pathways fit into the current theories. Insights into the mechanisms involving gene expression in diabetic neuropathy can help pinpoint genes with altered expression. This will help in the development of novel alternative therapeutic strategies to significantly slow the progression of neuropathy in susceptible individuals and perhaps even prevention. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. 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 (Pdiabetic 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 Pdiabetic 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.

  15. Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus.

    Science.gov (United States)

    Pai, Yen-Wei; Lin, Ching-Heng; Lee, I-Te; Chang, Ming-Hong

    2017-09-28

    To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese. A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire. In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (Pdiabetic peripheral neuropathy, whereas older age (Pdiabetic peripheral neuropathy with neuropathic pain. During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  16. [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).

  17. [Does autonomic diabetic neuropathy influence microcirculation reactivity in adolescents with diabetes type 1?].

    Science.gov (United States)

    Urban, Mirosława; Peczyńska, Jadwiga; Kowalewski, Marek; Głowińska-Olszewska, Barbara

    2007-01-01

    Microcirculation is known to be disturbed in many organs of diabetic patients. Retinopathy, nephropathy and neuropathy might be considered as the cause of the functional and morphological changes at the level of microcirculation. The aim of the study was to assess by means of dynamic capillaroscopy the influence of autonomic diabetic nephropathy (CAN) in adolescents with type 1 diabetes mellitus on capillary blood flow (CBV) in skin microcirculation. The study group consisted of 18 patients with type 1 diabetes mellitus (mean age 15+/-2 years). In 9 of them the diagnosis of CAN was made on the basis of Ewing tests. The control group consisted of 10 healthy persons aged 15+/-1.5 years. CBV was measured in capillars of the nailfold of the fourth finger during rest and after 2 minutes of arterial occlusion (the occlusion pressure - above 20 mmHg systolic blood pressure - was obtained by the occlusion of brachial artery using sphygnomanometer cuff). The resting CBV did not differ between patients with CAN, without CAN and healthy controls (0.39+/-0.06, 0.41+0.05 i 0.42+/-0.07). The values of the peak CBV significantly differ between the examined groups (CAN: 0.75+0.1; without CAN: 0.86+/-0.11; control group: 0.98+/-0.09, p<0.01). The obtained results indicate that the presence of the autonomic diabetic neuropathy significantly influences the regulatory function of microcirculation, which may predispose to occurrence of different late diabetic complications.

  18. Warm immersion recovery test in assessment of diabetic neuropathy--a proof of concept study.

    Science.gov (United States)

    Bharara, Manish; Viswanathan, Vijay; Cobb, Jonathan E

    2008-10-01

    The aim of this article was to present results of warm immersion recovery test in the diabetic foot with neuropathy using a liquid crystal-based contact thermography system. It is intended to provide a 'proof of concept' for promoting the role of supplementary thermal assessment techniques and evidence-based diagnosis of diabetic neuropathy. A total of 81 subjects from the outpatient department of MV Hospital for Diabetes, India, were assessed using a liquid crystal thermography system. Each subject was assigned to one of three study groups, that is diabetic neuropathy, diabetic non neuropathy and non diabetic healthy. The room temperature and humidity were consistently maintained at 24 degrees C and less than 50%, respectively, with air conditioning. The right foot for each subject was located on the measurement platform after warm immersion in water at 37 degrees C. Whole-field thermal images of the plantar foot were recorded for 10 minutes. Local measurements at the most prevalent sites of ulceration, that is metatarsal heads, great toe and heel, show highest temperature deficit after recovery for diabetic neuropathy group. The findings of the current study support the ones of a previous study by the authors, which used cold immersion recovery test for the neuropathic assessment of the diabetic foot. A temperature deficit between the recovery and the baseline temperature for the neuropathic group suggests degeneration of thermoreceptors. Thermal stimulus tests can be useful to validate the nutritional deficits' (during plantar loading and thermal stimulus) contribution in foot ulceration.

  19. 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.

  20. [Clinical improvement of diabetic neuropathy with carbamazepine or diclofenac treatment].

    Science.gov (United States)

    Tinoco-Samos, Andrea; Córdova-Pérez, Nydia; Arenas-Téllez, Juan Manuel; Vargas-Girón, Antonio; Zárate, Arturo; Hernández-Valencia, Marcelino

    2013-01-01

    diabetic neuropathy (DN) affects diverse aspects of a patient's life and there is not an optimal treatment. We did a comparative study of clinical improvement of DN with carbamazepine versus diclofenac. a prospective and longitudinal study of two groups with signs and symptoms of DN was done. One group had 30 patients who used carbamazepine with an initial dose of 200 mg, every 24 hours for one week, with a gradual increase of up to 200 mg every 6 hours for 10 months. The other group had 29 patients who used diclofenac sodium 100 mg every 12 hours. Bimonthly evaluations were made to graduate the pain according to the patients' perception and laboratory studies that included glucose and lipids profile. The statistical test used was ANOVA. the patients who used carbamazepine presented absence of pain after 10 months compared with the diclofenac group (p < 0.01). The presence of cramps, muscular strength, pulses, perception of temperature and pressure improved significantly (p < 0.05) with the use of carbamazepine. On the other hand, muscular strength, tact and perception of temperature were deteriorated with the use of diclofenac. it is important to provide the appropriate treatment to diabetic patients with DN.

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

    OpenAIRE

    Sacco, Isabel de Camargo Neves; João, Silvia Maria Amado; Alignani, Denise; Ota, Daniela Kinoshita; Sartor, Cristina Dallemole; Silveira, Leda Tomiko; Gomes, Aline Arcanjo; Cronfli, Regeane; Bernik, Márcia

    2005-01-01

    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 utiliz...

  3. Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: The Verona Diabetic Foot Screening Program.

    Science.gov (United States)

    Salvotelli, Laura; Stoico, Vincenzo; Perrone, Fabrizia; Cacciatori, Vittorio; Negri, Carlo; Brangani, Corinna; Pichiri, Isabella; Targher, Giovanni; Bonora, Enzo; Zoppini, Giacomo

    2015-01-01

    Somatic neuropathy is a chronic complication of diabetes. The purpose of our study was to determine prevalence and clinical variables associated with somatic neuropathy applying a simple screening method. All outpatients with type 2 diabetes attending our diabetic clinic were offered to participate into a diabetic foot screening program, in the period January 2004-December 2012. A total of 3,591 diabetic patients (55.5% men, age 68±10years) underwent detection of somatic neuropathy using the Michigan Neuropathy Screening Instrument in its parts of symptoms (administering a questionnaire) and clinical assessment slightly modified (evaluating foot inspection, vibration sensation by biothesiometer, ankle reflexes). The prevalence of somatic neuropathy was 2.2% in men and 5.5% in women (pneuropathy macro- and microvascular complications of diabetes were significantly more common. In multivariate logistic regression analyses BMI, HbA1c and ankle/brachial index independently predicted the presence of neuropathy. The prevalence of somatic neuropathy in type 2 diabetes is nearly 30% when searched with clinical examination. Poor metabolic control, excess body weight and peripheral arteriopathy are independent markers of somatic neuropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Prevalence and predictors of peripheral neuropathy in non-diabetic children with chronic kidney disease.

    Science.gov (United States)

    Yoganathan, Sangeetha; Bagga, Arvind; Gulati, Sheffali; Toteja, G S; Hari, Pankaj; Sinha, Aditi; Pandey, Ravindra Mohan; Irshad, Mohammad

    2017-11-29

    The aim of this study was to determine the prevalence and predictors of peripheral neuropathy in non-diabetic children with chronic kidney disease (CKD). Fifty-one consecutive normally nourished children, aged 3-18 years, with CKD stage IV and V of non-diabetic etiology were enrolled from May to December 2012. Nerve conduction studies were performed in fifty children. Blood samples were analyzed for the biochemical parameters, trace elements and micronutrients. The prevalence of peripheral neuropathy in our cohort was 52% (95% CI 37.65, 66.34). The majority (80.8%) had axonal neuropathy while 11.5% had demyelinating neuropathy. Isolated motor neuropathy was identified in 92.3% and sensorimotor neuropathy in 7.6%. The significant risk factors associated with peripheral neuropathy were older age, low serum copper and dialysis therapy. Electrodiagnostic studies should be performed in children with CKD to assess for peripheral neuropathy with the aim of optimizing medical care. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  5. Content validity of symptom-based measures for diabetic, chemotherapy, and HIV peripheral neuropathy.

    Science.gov (United States)

    Gewandter, Jennifer S; Burke, Laurie; Cavaletti, Guido; Dworkin, Robert H; Gibbons, Christopher; Gover, Tony D; Herrmann, David N; Mcarthur, Justin C; McDermott, Michael P; Rappaport, Bob A; Reeve, Bryce B; Russell, James W; Smith, A Gordon; Smith, Shannon M; Turk, Dennis C; Vinik, Aaron I; Freeman, Roy

    2017-03-01

    No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. © 2016 Wiley Periodicals, Inc.

  6. Diabetic peripheral neuropathy class prediction by multicategory support vector machine model: a cross-sectional study.

    Science.gov (United States)

    Kazemi, Maryam; Moghimbeigi, Abbas; Kiani, Javad; Mahjub, Hossein; Faradmal, Javad

    2016-01-01

    Diabetes is increasing in worldwide prevalence, toward epidemic levels. Diabetic neuropathy, one of the most common complications of diabetes mellitus, is a serious condition that can lead to amputation. This study used a multicategory support vector machine (MSVM) to predict diabetic peripheral neuropathy severity classified into four categories using patients' demographic characteristics and clinical features. In this study, the data were collected at the Diabetes Center of Hamadan in Iran. Patients were enrolled by the convenience sampling method. Six hundred patients were recruited. After obtaining informed consent, a questionnaire collecting general information and a neuropathy disability score (NDS) questionnaire were administered. The NDS was used to classify the severity of the disease. We used MSVM with both one-against-all and one-against-one methods and three kernel functions, radial basis function (RBF), linear, and polynomial, to predict the class of disease with an unbalanced dataset. The synthetic minority class oversampling technique algorithm was used to improve model performance. To compare the performance of the models, the mean of accuracy was used. For predicting diabetic neuropathy, a classifier built from a balanced dataset and the RBF kernel function with a one-against-one strategy predicted the class to which a patient belonged with about 76% accuracy. The results of this study indicate that, in terms of overall classification accuracy, the MSVM model based on a balanced dataset can be useful for predicting the severity of diabetic neuropathy, and it should be further investigated for the prediction of other diseases.

  7. The Application of SUDOSCAN for Screening Diabetic Peripheral Neuropathy in Chinese Population Screening DPN by SUDOSCAN.

    Science.gov (United States)

    Jin, Jiewen; Wang, Weimin; Gu, Tianwei; Chen, Wei; Lu, Jing; Bi, Yan; Zhu, Dalong

    2017-09-11

    Purpose Diabetic peripheral neuropathies are the common chronic complications of diabetes, but the diagnosis is insensitive by physical examination in busy outpatients. Here we evaluated the performance of SUDOSCAN in screening diabetic peripheral neuropathies in Chinese type 2 diabetic patients. Methods The study enrolled 180 patients for annually screening. All patients underwent neurological symptoms assessment, clinical examination, nerve conduction studies and cardiovascular autonomic reflex tests. SUDOSCAN was tested and evaluated with electrochemical skin conductance in hands and feet, asymmetry ratio in hands and feet and predicted cardiac neuropathy. Results Patients enrolled had an average age of 56.1 years, 9.8 years of diabetic duration. Patients with diabetic sensorimotor polyneuropathy showed significantly lower electrochemical skin conductance in feet and higher asymmetry ratio in feet compared with those without. Sensitivity and specificity of asymmetry ratio in feet for diagnosing diabetic sensorimotor polyneuropathy were 88.2% and 46.9% and area under ROC curve was 0.713. Patients with cardiovascular autonomic neuropathy showed significantly lower electrochemical skin conductance in hands and feet, and higher asymmetry ratio in feet and predicted cardiac neuropathy compared with those without. Sensitivity and specificity of electrochemical skin conductance in feet in diagnosing cardiovascular autonomic neuropathy were 85.6% and 76.1% with an area under ROC curve of 0.859. Conclusions SUDOSCAN is a sensitive test to detect diabetic peripheral neuropathy in China and could be an effective screening tool in in busy outpatients and primary health care. © Georg Thieme Verlag KG Stuttgart · New York.

  8. 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. © The Author(s) 2015.

  9. IMPACT OF GLYCEMIC CONTROL ON OXIDATIVE STRESS AND ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    Shilpashree

    2015-01-01

    Full Text Available INTRODUCTION: Oxidative stress due to enhanced free - radical generation and/or a decrease in antioxidant defense mechanisms has been implicated in the pathogenesis of diabetic neuropathy. This study was conducted to study the impact of glycemic control on oxidative stress and antioxidant balance in diab etic neuropathy. METHOD S : fifty patients with diabetic neuropathy and fifty age matched healthy controls were included in the study. Glycosylated hemoglobin (HbA1c was estimated to assess the severity of diabetes and the glycemic control. Serum malondiaal dehyde (MDA levels were assessed as a marker of lipid peroxidation and hence oxidative stress. Superoxide Dismutase (SOD levels were assessed for antioxidant status. RESULTS: Significant positive correlation was found between serum MDA levels and hba1c ( r = 0.276, p < 0.0001 in patients with diabetic neuropathy. There was statistically significant reduction in the Glutathione peroxidase levels. Further, SOD levels were inversely correlated with HbA1c (r= - 0.603, p<0.0001 levels. CONCLUSION AND SUMMARY: oxidative stress is greatly increased in patients suffering from diabetic neuropathy and is inversely related to glycemic control. This may be due to depressed antioxidant enzyme levels and may also be responsible for further depletion of antioxidant enzym e GPx. This worsens the oxidative stress and creates a vicious cycle of imbalance of free radical generation and deficit of antioxidant status in these patients which may lead to nervous system damage causing diabetic neuropathy. A good glycemic control is essential for prevention of diabetic neuropathy.

  10. The protective effect of losartan on diabetic neuropathy in a diabetic rat model.

    Science.gov (United States)

    Cavusoglu, T; Karadeniz, T; Cagiltay, E; Karadeniz, M; Yigitturk, G; Acikgoz, E; Uyanikgil, Y; Ates, U; Tuglu, M I; Erbas, O

    2015-09-01

    Involvement of the peripheral and autonomic nervous systems is possibly the most frequent complication of diabetes. Important risk factors included hyperglycemia, dyslipidemia, hypertension, and smoking. Angiotensin-converting-enzyme inhibitor (ACE) inhibitors should be beneficial in all vascular beds, including neuropathy and retinopathy. In this study we aimed to evaluate the effect of the angiotensin receptor blocker losartan on diabetic neuropathy in a diabetic rat model. 24 male, Sprague Dawley albino mature rats were divided into 3 groups; (1) control group: No drug was administered to the remainder of rats which blood glucose levels were under 120 mg/dl, (2) diabetic control: rats were given no medication, but 4 ml per day of tap water was given by oral gavage, (3) losartan groups: rats were given 10 mg/kg/day oral of losartan for 4 weeks. Electromyography (EMG) was applied to anesthetized rats at the end of 4(th) weekend. Then, the animals were euthanized and sciatic nerve was performed for histopathological examination. Compound Muscle Action Potential (CMAP) amplitude of diabetic rats receiving the Saline in the EMG was significantly reduced when compared to the control group. Distal latency value and CMAP duration of diabetic rats receiving the saline were meaningfully increased when compared to the control group. CMAP amplitude and CMAP duration of diabetic rats receiving the Losartan treatment in the EMG were meaningfully reduced when compared to diabetic rats receiving the Saline.Perineural thickness in the rats receiving the Losartan treatment was found to be significantly reduced when compared to the group receiving the Saline. As a result, it has been shown in this study that perineural thickness of the Losartan treatment was significantly reduced when compared to saline receiving group, significantly increased the immunoexpression of NGF, and also provided a significantly recovery in EMG when compared to Saline receiving group. © Georg

  11. [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.

  12. Prevalence and clinical features of atrial fibrillation in diabetic neuropathy: a cross-sectional, observational study.

    Science.gov (United States)

    Koçağra Yağız, İdil Gökçen; Bayata, Serdar; Yeşil, Murat; Kurt İncesu, Tülay; Arıkan, Erdinç; Postacı, Nursen

    2012-12-01

    This cross-sectional, observational study investigated prevalence and clinical features of atrial fibrillation (AF) in diabetic patient groups with or without autonomic neuropathy. One hundred and fourteen consecutive patients with pharmacologically treated type-II diabetes mellitus were enrolled for this study in our institution between January 2010 and December 2010. All patients underwent 12-lead electrocardiography on the day of enrollment for AF detection. All diabetic patients underwent neurologic examination for the presence of diabetic autonomic neuropathy (DAN). Following clinical evaluation, sympathetic skin responses (SSR) and RR interval variability (RRIV) analysis were used for the detection of autonomic neurologic involvement. Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of DAN. Patient groups with or without DAN were compared for AF occurrence. Continuous and categorical data were compared with independent samples t- test and Chi-square statistical tests respectively. Atrial fibrillation prevalence was 24% (n=29) in study population. Diabetic autonomic neuropathy was diagnosed in 47 (39%) patients. Basal characteristics of patients with or without DAN were comparable except glycosylated hemoglobin A (HbA1c) levels. HbA1c levels were found significantly higher in patients with DAN. Atrial fibrillation was diagnosed in 14 patients in Group 1 and in 15 patients in Group 2. Significantly increased AF prevalence (31.9% vs. 20.8%, p=0.014, in groups with and without DAN respectively) was observed in patient group with diabetic autonomic neuropathy. The results of this study demonstrated an increased prevalence of AF in patients with diabetic autonomic neuropathy compared with non-neuropathic, diabetic patients. Further investigation of this relation with prospective studies is needed to demonstrate a causal relationship between diabetic autonomic neuropathy and AF.

  13. Prevalence of Sensory Neuropathy in Type 2 Diabetes Mellitus and Its Correlation with Duration of Disease.

    Science.gov (United States)

    Karki, D B; Yadava, S K; Pant, S; Thusa, N; Dangol, E; Ghimire, S

    2016-01-01

    Background Peripheral neuropathy is one of the most common and distressing late complication of diabetes mellitus. Ignorance of the complications may develop foot ulcers and gangrene requiring amputation. Objective The main objective of this study is to find out the prevalence of sensory neuropathy in type 2 diabetes mellitus and to compare it with the duration of disease. Method Two hundred seventy one patients with type 2 diabetes mellitus of both gender age 30 years and above willing to participate were included in this study. Patients having hypothyroidism, rheumatoid arthritis, B12 deficiency, cerebrovascular disease, chronic musculoskeletal disease, Parkinson's disease, alcohol abuse, chronic renal or liver failure and cancer were excluded from the study. Touch, pin prick and vibration sensation were tested. Vibration perception threshold was recorded from six different sites of the sole of each foot using Biothesiometer. Result Two hundreds seventy one type 2 diabetic outpatients were studied. The mean age was 59.81±22.85 years. The overall prevalence of diabetic sensory neuropathy in the study population was 58.70%. A rising trend of diabetic sensory neuropathy with increasing age and duration of diabetes was observed. Neuropathy was found more in patients having urinary microalbuminuria. Burning and pins and needles sensation were most common symptoms. Conclusion The overall prevalence of diabetic sensory neuropathy in the study population was 58.70% (mean age 59.81±22.85 yrs), and its prevalence increased with duration of diabetes and increasing age. Its prevalence was found more in patients having microalbuminuria.

  14. ERECTILE DYSFUNCTION WITHIN THE PATIENTS WITH AUTONOMIC DIABETIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    E. A. Povelitsa

    2017-01-01

    Full Text Available Objective: diagnostics of erectile disorders within men with diabetic autonomic neuropathy and detection of rehabilitation methods of patients with erectile dysfunction (ED affected diabetes mellitus (DM.Materials and methods. Thirty patients with DM were examined (15 patients with type 1 and 15 patients with type 2 respectively. Patients with DM had ED mainly of severe form (IIEF-5  from 6 to 16 points. According to the results of conducted examination the patients were prescribed the course of conservative therapy including hosphodiesterase in hibitors of type V, anticholinesterase drugs, drugs of thioctic acid. Conservative therapy was combined with shock wave therapy in the area of the penis. The group for comparison consisted of 15 healthy men (volunteers without signs of ED (IIEF-5 21–22 points. Immune-enzyme analysis was used for detection of sex hormone status. Ultrasound, dopplerographic and X-ray methods were used for conduction of angiography of pool vessels of internal pudendal artery (IPA. Electroneuromyography of penis nerves was conducted.Results. According to the conducted research patients with DM were diagnosed with cavernous fibrosis, angiosclerosis of IPA and penis vessels in 100 % cases. Axonopathy of motor and sensory nerves of penis was detected in 100 % cases, stenosis and occlusion changes in IPA were detected in 42.9 % cases causing disorder and insufficiency in arterial perfusion in IPA pool.Conclusion. Denervation changes in sensory and motor nerves of penis and hemodynamicly significant perfusion disorders in IPA pool were principal pathogenetic factors of ED within the patients with DM. Decrease of reaction of IPA to the pharmacological stimulation was noted within patients with DM, which was caused by the angiosclerosis and loss of arterial wall elasticity. There was noted inefficiency of conservative therapy within patients with DM and ED at severe stage.

  15. Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of simple clinical tests for the screening of vibration perception threshold at primary care level.

    Science.gov (United States)

    Azzopardi, Kurt; Gatt, Alfred; Chockalingam, Nachiappan; Formosa, Cynthia

    2017-10-10

    Diabetic peripheral neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The aim of this study was to compare different screening modalities in the detection of diabetic peripheral neuropathy in a primary care setting. A prospective non-experimental comparative multi-centre cross sectional study was conducted in various Primary Health Centres. One hundred participants living with Type 2 diabetes for at least 10 years were recruited using a convenience sampling method. The Vibratip, 128Hz tuning fork and neurothesiometer were compared in the detection of vibration perception. This study showed different results of diabetic peripheral neuropathy screening tests, even in the same group of participants. This study has shown that the percentage of participants who did not perceive vibrations was highest when using the VibraTip (28.5%). This was followed by the neurothesiometer (21%) and the 128Hz tuning fork (12%) (pneuropathy in patients with diabetes is crucial. This study demonstrates that some instruments are more sensitive to vibration perception than others. We recommend that different modalities should be used in patients with diabetes and when results do not concur, further neurological evaluation should be performed. This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  16. Vascular Impairment of Epineurial Arterioles of the Sciatic Nerve: Implications for Diabetic Peripheral Neuropathy

    Science.gov (United States)

    Yorek, Mark A.

    2015-01-01

    This article reviews the impact of diabetes and its treatment on vascular function with a focus on the reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve. Another focus is the relationship between the dysregulation of neurovascular function and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. The etiology involves metabolic, vascular, and immunologic pathways besides neurohormonal growth factor deficiency and extracellular matrix remodeling. In the light of this complex etiology, an effective treatment for diabetic peripheral neuropathy has not yet been identified. Current opinion postulates that any effective treatment for diabetic peripheral neuropathy will require a combination of life style and therapeutic interventions. However, a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed before such a treatment strategy can be developed. After reading this review, the reader should have gained insight into the complex regulation of vascular function and blood flow to the sciatic nerve, and the impact of diabetes on numerous elements of vascular reactivity of epineurial arterioles of the sciatic nerve. PMID:26676659

  17. 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

    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

  18. 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.

  19. Severe, early axonal degeneration following experimental anterior ischemic optic neuropathy.

    Science.gov (United States)

    Lee, Gun Ho; Stanford, Madison P; Shariati, Mohammad A; Ma, Jeffrey H; Liao, Yaping Joyce

    2014-09-23

    Anterior ischemic optic neuropathy (AION) is the most common acute optic neuropathy in adults older than 50 and leads to axonal degeneration, thinning of the retinal nerve fiber layer and loss of the retinal ganglion cells (RGCs). We used experimental AION model to study early axonal changes following ischemia. We induced optic nerve head ischemia in adult mice using photochemical thrombosis and analyzed retinal changes within 1 week. We used confocal scanning laser ophthalmoscopy (cSLO) and fluorescence microscopy of retinal whole mount preparations to analyze axonal degeneration in Thy1-YFP-H mice and those injected with annexin-V-A488 intravitreally. Three days after AION, morphometric analyses in Thy1-YFP-H mice revealed evidence of early axonal changes, including swollen or branched axonal stumps. There was also a beads-on-a-string appearance of YFP expression. The axonal enlargements occurred at an interval of 17 ± 1 μm or 6 ± 0 enlargements/100 μm. At day 7 after AION, the degenerating intraretinal RGC axons exhibited intense annexin-V-A488 staining (P = 0.002). The annexin-V staining pattern was fragmented, with intersegment interval of 20.1 ± 1.4 μm or 5.8 ± 0.4 annexin-V-A488(+) fragments/100 μm, which were similar to that of degenerating Thy1-YFP(+) axons. Following a photochemical thrombosis model of AION, RGC axons displayed severe degenerative changes within 1 week, suggesting that after ischemia, RGC axons may degenerate in a temporally and spatially distinct fashion from that of the soma. Our findings also further established annexin-V as a useful marker of retinal degeneration because it strongly labeled dying RGC axons. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  20. Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice.

    Science.gov (United States)

    Yorek, Matthew S; Obrosov, Alexander; Shevalye, Hanna; Lupachyk, Sergey; Harper, Matthew M; Kardon, Randy H; Yorek, Mark A

    2014-09-01

    We sought to determine the impact that duration of hyperglycemia and control has on corneal nerve fiber density in relation to standard diabetic neuropathy endpoints. Control and streptozotocin-diabetic C57Bl/6J mice were analyzed after 4, 8, 12, and 20 weeks. For the 20-week time point, five groups of mice were compared: control, untreated diabetic, and diabetic treated with insulin designated as having either poor glycemic control, good glycemic control, or poor glycemic control switched to good glycemic control. Hyperglycemia was regulated by use of insulin-releasing pellets. Loss of corneal nerves in the sub-epithelial nerve plexus or corneal epithelium progressed slowly in diabetic mice requiring 20 weeks to reach statistical significance. In comparison, slowing of motor and sensory nerve conduction velocity developed rapidly with significant difference compared with control mice observed after 4 and 8 weeks of hyperglycemia, respectively. In diabetic mice with good glycemic control, average blood glucose levels over the 20-week experimental period were lowered from 589 ± 2 to 251 ± 9 mg/dl. All diabetic neuropathy endpoints examined were improved in diabetic mice with good glycemic control compared with untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy. © 2014 Peripheral Nerve Society.

  1. Inhibition of Adenylyl Cyclase in the Spinal Cord Alleviates Painful Diabetic Neuropathy in Zucker Diabetic Fatty Rats.

    Science.gov (United States)

    Feng, Hao; Lu, Guodong; Li, Qingsong; Liu, Zhonghao

    2017-04-01

    Diabetic neuropathy is the most common complication of both type 1 and type 2 diabetes. In this study, we tested the hypotheses that impaired Gi protein expression/function in the spinal cord is associated with the development of painful neuropathy in people with type 2 diabetes and that reduction of cyclic adenosine monophosphate (cAMP) production by inhibiting adenylyl cyclase in the spinal cord can alleviate diabetic neuropathy. To this end, we examined the levels of cAMP, cAMP-dependent protein kinase (PKA) and cAMP response element-binding protein (CREB) in the spinal cord after the development of neuropathic pain in Zucker diabetic fatty (ZDF) rats with type 2 diabetes. We evaluated the effects of intrathecal injections of SQ22536, an adenylyl cyclase inhibitor, on mechanical allodynia and thermal hyperalgesia in rats with painful diabetic neuropathy. We found that diabetic ZDF rats exhibited mechanical allodynia and thermal hyperalgesia, which are associated with enhanced cAMP production, increased PKA activation and elevated CREB phosphorylation in the spinal cord. Additionally, diabetic ZDF rats exhibited attenuated expression of Giα, but not Gsα, in the spinal cord. Furthermore, intrathecal administrations of SQ22536 dose-dependently alleviated mechanical allodynia and thermal hyperalgesia in diabetic ZDF rats and reduced cAMP production, PKA activation and p-CREB expression in the spinal cord. Taken together, our study suggested that cAMP-mediated signalling in the spinal cord is likely critical for the development of painful neuropathy in people with type 2 diabetes. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

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

    OpenAIRE

    Misra, Stuti L.; Dipika V Patel; McGhee, Charles N. J.; Monika Pradhan; Dean Kilfoyle; Braatvedt, Geoffrey D; Craig, Jennifer P.

    2014-01-01

    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 ...

  3. Chromosomal Aberrations and Exon 1 Mutation in the AKR1B1 Gene in Patients with Diabetic Neuropathy.

    Science.gov (United States)

    Saraswathy, Radha; Anand, Sudhaa; Kunnumpurath, Sree Kumar; Kurian, R Jones; Kaye, Alan David; Vadivelu, Nalini

    2014-01-01

    Recent decades have seen an increase in our understanding of a number of pathophysiological processes associated with type 2 diabetes mellitus (DM). Despite increases in understanding and treatment options, diabetic neuropathy remains a significant problem and is associated with tremendous morbidity and mortality. In this regard, oxidative DNA damage is postulated to play a role in diabetes-mediated neuropathic pathogenesis. In this pilot investigation, we studied the extent of chromosomal damage utilizing chromosomal aberration (CA) assay in cultured lymphocytes of patients in 3 subgroups: patients with diabetic neuropathy, patients with type 2 DM and no neuropathy, and a control group. The patients with diabetic neuropathy showed a statistically significantly higher rate of CA (Pneuropathy (0.03 ± 0.02). Samples from subjects with diabetic neuropathy were evaluated to check for mutations in the AKR1B1 gene (exon 1). A significant number of mutations appeared after DNA sequencing within the AKR1B1 gene. Of 50 diabetic neuropathy patient samples analyzed, 10 revealed mutations. Our results suggest that painful diabetic neuropathy is a condition with enhanced genomic instability characterized by increased CA and possible mutations. Exon 1 of the gene AKR1B1 showed significant mutations in patients with painful diabetic neuropathy.

  4. Effect of Atibalamula and Bhumyamalaki on thirty-three patients of diabetic neuropathy.

    Science.gov (United States)

    Patel, Kalapi; Patel, Manish; Gupta, S N

    2011-07-01

    Diabetic neuropathy is a relatively early and common complication affecting approximately 30% of diabetic patients. According to Ayurvedic principles there is involvement of Vata and Pitta Dosa in diabetic neuropathy. Bhumyamalaki (Phyllanthus niruri) is a plant which shows possibility to pacify these two Dosas. Another plant Atibala (Abutilon indicum) has also Vata pacifying qualities. Present study has been carried out to study the effects of Bhumyamalaki and Atibala on 33 patients of diabetic neuropathy. All the patients have been given Bhumyamalaki Churna 3 g twice a day and decoction of 10 g of Atibala-mula twice a day for 30 days. Neuropathy analyzer machine has been used for exact recording of sensory perception of vibration, cold and hot sensations before and after treatment. Changes in numbness, tingling, burning sensation and pain in lower limbs have also been assessed before and after treatment. Results have been analyzed statistically by applying the 't' test. It can be stated from the results that use of Bhumyamalaki and Atibalamula in the patients of diabetic neuropathy can revert the diminished sensory perception and can reduce the symptoms significantly.

  5. [Association between neuropathy and peripheral vascular insufficiency in patients with diabetes mellitus type 2].

    Science.gov (United States)

    Millán-Guerrero, Rebeca O; Vásquez, Clemente; Isaís-Millán, Sara; Trujillo-Hernández, Benjamín; Caballero-Hoyos, Ramiro

    2011-01-01

    Diabetes mellitus (DM) can present complications of neuropathy and peripheral arterial disease with high risk for developing foot ulcers and consequent amputations. To identify the association between peripheral vascular disease, and neuropathy in type 2 Diabetes mellitus patients from the Hospital General de Zona No. 1 IMSS in Colima, Mexico. Cross-sectional study of 80 patients with diabetes mellitus evaluated by means of the Edinburgh Claudication Questionnaire, Michigan Neuropathy Screening Instrument, ankle-arm index, Motor Nerve Conduction Velocity and H-reflex. 51 women and 29 men were studied. Mean age was 53.9 +/- 9.6 years, mean diabetes mellitus progression was 8 +/- 6.6 years and mean glucose level was 283 +/- 110 mg/mL. Neuropathy presented in 65 patients (81.2%). Ankle/arm index revealed 19% of patients presented with moderate peripheral vascular insufficiency. Motor Nerve Conduction Velocity was abnormal in 40% of patients and H-reflex was absent in 70%. Grade 2 motor-sensitive polyneuropathy was found in 70-80% of patients and moderate peripheral vascular insufficiency in 19%. It can thus be inferred that the complication of diabetic neuropathy appears before that of peripheral vessel damage.

  6. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    Science.gov (United States)

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

  7. Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy.

    Science.gov (United States)

    Stavniichuk, Roman; Shevalye, Hanna; Lupachyk, Sergey; Obrosov, Alexander; Groves, John T; Obrosova, Irina G; Yorek, Mark A

    2014-11-01

    Peroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP-ribosylation), mitochondrial dysfunction and impaired stress signalling, as well as protein nitration. In this study, we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes. C57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (-)-epicatechin gallate (20 mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia. Untreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fibre dysfunction without alleviation of hyperglycaemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fibre density were found with FeTMPS treatment only. Peroxynitrite injury and protein nitration are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts for treatment of diabetic peripheral neuropathy. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. 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. © 2016 Elsevier Inc. All rights reserved.

  9. Clinical evaluation of a new device in the assessment of peripheral sensory neuropathy in diabetes.

    Science.gov (United States)

    Bracewell, N; Game, F; Jeffcoate, W; Scammell, B E

    2012-12-01

    Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a Neurotip™ and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at ≥ 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  10. Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy.

    Science.gov (United States)

    Yigit, Serbulent; Karakus, Nevin; Inanir, Ahmet

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. Methylenetetrahydrofolate reductase (MTHFR) gene variants have been associated with vasculopathy that has been linked to diabetic neuropathy. The aim of the present study was to investigate the possible association between MTHFR gene C677T mutation and DPN and evaluate if there is an association with clinical features in a relatively large cohort of Turkish patients. The study included 230 patients affected by DPN and 282 healthy controls. Genomic DNA was isolated and genotyped using the polymerase chain reaction-based restriction fragment length polymorphism assay for the MTHFR gene C677T mutation. The genotype and allele frequencies of the C677T mutation showed statistically significant differences between the patients with DPN and the controls (p=0.003 and p=0.002, respectively). After the patients with DPN were stratified according to clinical and demographic characteristics, a significant association was observed between the C677T mutation and history of retinopathy (p=0.039). A high association between the MTHFR gene C677T mutation and DPN was observed in the present study. In addition, history of retinopathy was associated with the MTHFR C677T mutation in patients with DPN.

  11. 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...

  12. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes?

    Science.gov (United States)

    Hardt, Philip D; Ewald, Nils

    2011-01-01

    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.

  13. 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.

  14. 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...

  15. 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...

  16. Metformin Protects against Experimental Acrylamide Neuropathy in Rats.

    Science.gov (United States)

    Oda, Samah S

    2017-11-01

    Preclinical Research To investigate the potential neuroprotective effects of metformin against experimental acrylamide neuropathy in rats, 24 rats were distributed into four equal groups (6 each). Group 1 was kept as a control. Group 2 (MET) was orally given metformin (200 mg/kg BW/day). Group 3 (ACR) was injected IP with acrylamide (50 mg/kg BW/day). Animals in group 4 (ACR + MET) were administered both MET and ACR at the same dose and route used in groups 2 and 3. Treatments were administered three times a week for three weeks. ACR induced an increase in lipid peroxidation in brain and spinal cord. This was associated with down regulation of bcl2 and up regulation of caspase3 in cerebrum, cerebellum, spinal cord, and sciatic nerve in the ACR-treated group. ACR-treated rats revealed neuronal degeneration and glial cell reaction in brain and spinal cord with axonal degeneration and myelin sheath irregularities in sciatic nerve. MET restored lipid peroxidation in brain and spinal cord, decreased caspase3 activity and up regulated bcl2 expression in cerebrum and sciatic nerve. Histopathological findings in ACR + MET group were lesser severe than those established in ACR-group indicating that MET ameliorates the neuropathic effects of ACR in rats. Drug Dev Res 78 : 349-359, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

    Science.gov (United States)

    Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

    2017-12-13

    In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Neuropathy and poorly controlled diabetes increase the rate of surgical site infection after foot and ankle surgery.

    Science.gov (United States)

    Wukich, Dane K; Crim, Brandon E; Frykberg, Robert G; Rosario, Bedda L

    2014-05-21

    This prospective study was designed to evaluate the frequency of surgical site infection in patients treated with foot and ankle surgery. Our hypothesis was that patients with complications of diabetes are at increased risk for surgical site infection compared with patients without diabetes and patients with diabetes who do not have diabetic complications. Another goal was to compare the association of neuropathy with surgical site infection in both nondiabetic and diabetic patients. Two thousand and sixty consecutive surgical cases were evaluated. Group 1 included nondiabetic patients without neuropathy, Group 2 included nondiabetic patients with neuropathy, Group 3 included patients with diabetes but no diabetic complications, and Group 4 included patients with diabetes who had at least one complication of diabetes. The surgical site infection rate in this study was 3.1%. Patients with complicated diabetes had a 7.25-fold increased risk of surgical site infection compared with nondiabetic patients without neuropathy and a 3.72-fold increased risk compared with patients with uncomplicated diabetes. Patients with complicated diabetes had a nonsignificant 1.54-fold higher rate of surgical site infection compared with nondiabetic patients with neuropathy. Nondiabetic patients with neuropathy had a significant 4.72-fold increased risk of surgical site infection compared with nondiabetic patients without neuropathy. Despite this, nondiabetic patients with neuropathy did not have a significantly higher rate of surgical site infection than patients with uncomplicated diabetes, and the frequency of surgical site infection in the group with uncomplicated diabetes was not significantly different from that in the nondiabetic patients without neuropathy. Multivariable logistic regression analysis demonstrated that peripheral neuropathy and a hemoglobin A1c of ≥8% were independently associated with surgical site infection. Complicated diabetes increases the risk of surgical

  19. Behavioral changes of Wistar rats with experimentally-induced painful diabetic neuropathy Mudança do comportamento de ratos Wistar no modelo experimental de neuropatia diabética dolorosa

    Directory of Open Access Journals (Sweden)

    JOSÉ ARTUR C. D'ALMEIDA

    1999-09-01

    Full Text Available With the purpose of studying data on spontaneous customary changes in diabetic rats, we induced diabetes in 28 Wistar rats with streptozotocin. The animals were observed for 27 weeks in an attempt to characterize spontaneous customary changes that could suggest signs of chronic pain. Morphine, as a central-acting potent analgesic and its specific antagonist naloxone, were used. Our results evidenced in the animals a clinical syndrome similar to human diabetes. Long-term customary analysis revealed a significant (pCom o objetivo de estudar dados sobre mudança de comportamento em ratos com neuropatia diabética dolorosa, induzimos diabetes em 28 ratos Wistar com estreptozotocina. Os animais foram então observados ao longo de 27 semanas com o propósito de caracterizar mudanças espontâneas em seus hábitos que pudessem sugerir sinais de dor crônica. Morfina como um potente analgésico de ação central e seu antagonista específico naloxona foram utilizados. Nossos resultados evidenciaram nos animais uma síndrome clínica semelhante ao diabetes humano (poliúria, catarata, perda de peso, neuropatia sensitivo-motora de predomínio distal. A análise comportamental revelou aumento dos comportamentos de coçar-se e descansar/dormir, e diminuição das atividades motoras e hábitos de comer e limpar-se. Além disso, os testes térmicos revelaram sinais de hiperalgesia em 43% desses animais, o que corrobora o significado de coçar-se como sinal de dor. Os testes farmacológicos com morfina evidenciaram inibição significativa (p<0,05 no hábito de coçar-se, com aumento recíproco das atividades motoras e de alimentar-se, e diminuição do tempo de descansar/dormir. A naloxona antagonizou os efeitos da morfina. Tais resultados sugerem que esses animais exibiram comportamento evocado de hiperalgesia e que o hábito de coçar-se é possivelmente uma manifestação espontânea de dor crônica nesse modelo de neuropatia diabética dolorosa em ratos

  20. 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

  1. 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 m......, whereas in type 2 CAN was associated with macrovascular risk factors.......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...... by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed. The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1...

  2. Date Fruit Extract Is a Neuroprotective Agent in Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats: A Multimodal Analysis

    Science.gov (United States)

    Zangiabadi, Nasser; Asadi-Shekaari, Majid; Sheibani, Vahid; Jafari, Mandana; Shabani, Mohammad; Asadi, Ali Reza; Tajadini, Hale; Jarahi, Morteza

    2011-01-01

    Background. To study the effects of an aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae) diet on diabetic polyneuropathy (DPN) in streptozotocin- (STZ-) induced diabetic rats. Methods. The effects of a date fruit extract (DFE) diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with a nondiabetic control group, diabetic control group (sham), and vehicle group with respect to the following parameters: open field behavioral test, motor nerve conduction velocity (MNCV), and morphological observations. Results. In the model of STZ-induced of diabetic neuropathy, chronic treatment for 6 weeks with DFE counteracted the impairment of the explorative activity of the rats in an open field behavioral test and of the conduction velocity of the sciatic nerve (MNCV). In addition, pretreatment with DFE significantly reversed each nerve diameter reduction in diabetic rats. Conclusion. DFE treatment shows efficacy for preventing diabetic deterioration and for improving pathological parameters of diabetic neuropathy in rats, as compared with control groups. PMID:22191015

  3. Physical activity, glycemic control, and diabetic peripheral neuropathy: a national sample.

    Science.gov (United States)

    Loprinzi, Paul D; Hager, Kathy K; Ramulu, Pradeep Y

    2014-01-01

    To determine if physical activity and/or blood glycohemoglobin (HbA1c) are associated with the prevalence of peripheral neuropathy (PN) in a representative population of diabetics. Three hundred thirty-nine diabetic participants (40-85 yrs) taking part in 2003-2004 National Health and Nutrition Examination Survey were studied. Participants were defined as having peripheral neuropathy if examination determined ≥1 insensate area in either foot. Moderate-to-vigorous physical activity (MVPA) was objectively-measured using accelerometry. After adjustments, MVPA was not significantly associated with PN (OR=1.16; 95% CI: 0.48-2.78), nor was HbA1c (OR=0.55; 95% CI: 0.28-1.04). However, there was evidence of statistical interaction (OR=0.24; 95% CI: 0.06-0.87) between MVPA and HbA1c status, showing that diabetics engaging in higher levels of MVPA and having normal HgbA1c levels were less likely to have PN than what would be expected based on the individual effects of MVPA and HbA1c alone. Although MVPA was not directly associated with PN, these findings suggest that proper physical activity, coupled with good glycemic control, is associated with less neuropathy. Future longitudinal studies are required to evaluate whether physical activity and improved glycemic control may help prevent or slow the progression of diabetic end-organ damage, particularly diabetic neuropathy. © 2013.

  4. Peripheral neuropathy in patients with diabetes mellitus presenting as Bell's palsy.

    Science.gov (United States)

    Kiziltan, Meral E; Akalin, M Ali; Sahin, Rahsan; Uluduz, Derya

    2007-11-12

    The aim of this study is to evaluate the peripheral nerves in diabetes mellitus with or without peripheral facial paralysis (PFP). A total of 49 diabetic patients with PFP within the last year (23 females, mean age 60.3 +/- 9.3), and 83 diabetic patients without PFP (41 females, mean age 59.5 +/- 9.9) were enrolled. The neurological examination, eye-blinking response, needle EMG and electrophysiological parameters of peripheral nerves were evaluated. The neuropathic pain, other positive and negative sensory symptoms were statistically more frequent in controls than the PFP group, while no difference was noted in total neuropathy score. Sural sensorial nerve action potential amplitudes were same in both groups, but median nerve amplitudes were significantly lower in the PFP group. It is suggested that PFP is not a part of multifocal neuropathy in diabetes mellitus. However, at least some parts of the nerve conduction studies were involved, focal neuropathies were more frequent while sensory neuropathies with small nerve fiber involvement were less frequent in diabetes patients with PFP.

  5. 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.

  6. The role of insulin resistance in diabetic neuropathy in Koreans with type 2 diabetes mellitus: a 6-year follow-up study.

    Science.gov (United States)

    Cho, Yu Na; Lee, Kee Ook; Jeong, Julie; Park, Hyung Jun; Kim, Seung-Min; Shin, Ha Young; Hong, Ji-Man; Ahn, Chul Woo; Choi, Young-Chul

    2014-05-01

    We previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy. This study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period. Low HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012. Diabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy.

  7. 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.

  8. In Zucker Diabetic Fatty rats, subclinical diabetic neuropathy increases in vivo lidocaine block duration but not in vitro neurotoxicity

    Science.gov (United States)

    Lirk, Philipp; Flatz, Magdalena; Haller, Ingrid; Hausott, Barbara; Blumenthal, Stephan; Stevens, Markus F.; Suzuki, Suzuko; Klimaschewski, Lars; Gerner, Peter

    2012-01-01

    Background and Objectives Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. Additionally, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity in vitro and block duration in vivo in a genetic animal model of diabetes mellitus type II. Methods In the first experiments, neurons harvested from control Zucker Diabetic Fatty (ZDF) rats were exposed to acute (24 hours) or chronic (72 hours) hyperglycemia, followed by incubation with lidocaine 40 mM (approximately 1%). In a second experiment, neurons harvested from control ZDF rats, or diabetic ZDF rats, were incubated with lidocaine, with or without SB203580, an inhibitor of the p38 Mitogen-Activated Protein Kinase. Finally, we performed sciatic nerve block (lidocaine 2%, 0.2 mL) in control or diabetic ZDF rats, and measured motor and nociceptive block duration. Results In vitro, neither acute nor chronic hyperglycemia altered neurotoxic properties of lidocaine. In vitro, incubation of neurons with lidocaine resulted in a slightly decreased survival ratio when neurons were harvested from diabetic (57 ± 19) as compared to control (64 ± 9 %) rats. The addition of SB203580 partly reversed this enhanced neurotoxic effect and raised survival to 71 ± 12 in diabetic and 66 ± 9 % in control rats, respectively. In vivo, even though no difference was detected at baseline testing, motor block was significantly prolonged in diabetic as compared to control rats (137 ± 16 min versus 86 ± 17 min). Conclusions In vitro, local anesthetic neurotoxicity was more pronounced on neurons from diabetic animals, but the survival difference was small. In vivo, subclinical neuropathy leads to substantial prolongation of block duration. We conclude that early diabetic neuropathy increases block duration, while the observed increase in toxicity was small. PMID:23011115

  9. Comparison of balance ability between patients with type 2 diabetes and with and without peripheral neuropathy.

    Science.gov (United States)

    Lim, Kil-Byung; Kim, Dong Jun; Noh, Jeong-hyun; Yoo, Jeehyun; Moon, Jung-Wha

    2014-03-01

    (1) To examine the effects of peripheral neuropathy on balance stability in patients with type 2 diabetes, and (2) to assess static and dynamic balance and functional limitations. A cross-sectional study. Outpatient clinic. Subjects with type 2 diabetes and healthy subjects (n = 60) were divided into 3 groups: subjects with diabetes and with established peripheral neuropathy (diabetic peripheral neuropathy [DPN] group) (n = 17), subjects with diabetes and without peripheral neuropathy (diabetic control group) (n = 25), and subjects without diabetes (nondiabetic control [NDC] group) (n = 18). Sensory impairment assessment, motor impairment assessment, and functional limitation assessment were assessed by using the Balance Master system. In motor impairment assessment, left-to-right directional control in the rhythmic weight shift was significantly poorer in the diabetic control group than in the NDC group during slow movement (P = .027). During fast movement, it was poorer in the DPN group than in the NDC group (P = .022). In the unilateral stance test of functional limitation assessment with both eyes open, the mean center of gravity sway velocity was significantly higher in the DPN group than in the NDC group (P = .011 for the left leg standing, P = .008 for the right leg standing) and higher in the DPN group than in the diabetic control group (P = .027 for the right leg standing). In the tandem walk test, walking speed was significantly lower in the DPN group than in the NDC group (P = .033), and end sway was significantly greater in the DPN group than in the NDC group (P = .020). Analysis of the results of this study suggest that functional limitations may occur more in the patients with diabetes and with peripheral neuropathy, and dynamic balance stability may decrease more with the patients with diabetes than with the subjects without diabetes. Further studies on balance rehabilitation that concern dynamic balance stabilities and exercise

  10. Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets

    Science.gov (United States)

    Sandireddy, Reddemma; Yerra, Veera Ganesh; Areti, Aparna; Komirishetty, Prashanth

    2014-01-01

    In Diabetes, the chronic hyperglycemia and associated complications affecting peripheral nerves are one of the most commonly occurring microvascular complications with an overall prevalence of 50–60%. Among the vascular complications of diabetes, diabetic neuropathy is the most painful and disabling, fatal complication affecting the quality of life in patients. Several theories of etiologies surfaced down the lane, amongst which the oxidative stress mediated damage in neurons and surrounding glial cell has gained attention as one of the vital mechanisms in the pathogenesis of neuropathy. Mitochondria induced ROS and other oxidants are responsible for altering the balance between oxidants and innate antioxidant defence of the body. Oxidative-nitrosative stress not only activates the major pathways namely, polyol pathway flux, advanced glycation end products formation, activation of protein kinase C, and overactivity of the hexosamine pathway, but also initiates and amplifies neuroinflammation. The cross talk between oxidative stress and inflammation is due to the activation of NF-κB and AP-1 and inhibition of Nrf2, peroxynitrite mediate endothelial dysfunction, altered NO levels, and macrophage migration. These all culminate in the production of proinflammatory cytokines which are responsible for nerve tissue damage and debilitating neuropathies. This review focuses on the relationship between oxidative stress and neuroinflammation in the development and progression of diabetic neuropathy. PMID:24883061

  11. Acupuncture Treatment of Diabetic Peripheral Neuropathy in an American Indian Community.

    Science.gov (United States)

    Bailey, Anne; Wingard, Deborah; Allison, Matthew; Summers, Priscilla; Calac, Daniel

    2017-04-01

    Diabetic peripheral neuropathy (DPN) develops in 30% of type 2 diabetes patients, increases the risk for foot ulcers and amputation, and is a significant source of disability and medical costs. Treatment remains challenging, propelling research to focus on therapeutic methods that aim to improve blood circulation or ameliorate oxidative stress that drives development of DPN. The aim of this study was to assess the effectiveness of acupuncture treatment for DPN symptoms and lower extremity arterial circulation in people with type 2 diabetes. Twenty-five patients seen at a Southern California Tribal Health Center who reported a threshold level of diabetic neuropathy symptoms in the lower extremities during the previous 4 weeks received acupuncture treatment once per week over a 10-week period between 2011 and 2013. The Neuropathy Total Symptom Scale (NTSS-6), Neuropathy Disability Score (NDS), and laser Doppler fluxmetry (LDF) were used for assessment at baseline and 10 weeks. A total of 19 of 25 study participants completed the study and reported a significant reduction in the NTSS symptoms of aching pain, burning pain, prickling sensation, numbness, and allodynia. Lancinating pain did not decrease significantly. LDF measures improved but not significantly. Acupuncture may effectively ameliorate selected DPN symptoms in these American Indian patients. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

  12. 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

    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...

  13. Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus

    Czech Academy of Sciences Publication Activity Database

    Malá, Š.; Potočková, V.; Hoskovcová, L.; Pithová, P.; Brabec, Marek; Kulhánková, J.; Keil, R.; Riedlbauchová, L.; Brož, J.

    2017-01-01

    Roč. 134, December (2017), s. 139-144 ISSN 0168-8227 Institutional support: RVO:67985807 Keywords : autonomic neuropathy * diabetes mellitus * intima media thickness * therosclerosis * heart rate variability Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 3.639, year: 2016

  14. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping

    DEFF Research Database (Denmark)

    Hjortkjær, Henrik Øder; Jensen, Tonny; Kofoed, Klaus F

    2016-01-01

    OBJECTIVES: Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to t...

  15. 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.

    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

  16. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy

    NARCIS (Netherlands)

    de Vos, C.; de Vos, Cecile C.; Rajan, Vinayakrishnan; Steenbergen, Wiendelt; van der Aa, Hans E.; Buschman, H.P.J.

    2009-01-01

    Aim: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect

  17. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses development of neuropathy in diabetic rodents: Effects on peripheral sensory nerve function, structure and molecular changes.

    Science.gov (United States)

    Tsuboi, Kentaro; Mizukami, Hiroki; Inaba, Wataru; Baba, Masayuki; Yagihashi, Soroku

    2015-11-25

    Incretin-related therapy was found to be beneficial for experimental diabetic neuropathy, but its mechanism is obscure. The purpose of this study is to explore the mechanism through which dipeptidyl peptidase IV inhibitor, vildagliptin (VG), influences neuropathy in diabetic rodents. To this end, non-obese type 2 diabetic Goto-Kakizaki rats (GK) and streptozotocin (STZ)-induced diabetic mice were treated with VG orally. Neuropathy was evaluated by nerve conduction velocity (NCV) in both GK and STZ-diabetic mice, whereas calcitonin-gene-related peptide (CGRP) expressions, neuronal cell size of dorsal root ganglion (DRG) and intraepidermal nerve fiber density (IENFD) were examined in GK. DRG from GK and STZ-diabetic mice served for analyses of GLP-1 and insulin signaling. As results, VG-treatment improved glucose intolerance and increased serum insulin and GLP-1 in GK accompanied by the amelioration of delayed NCV and neuronal atrophy, reduced CGRP expressions and IENFD. Diet restriction alone did not significantly influence these measures. Impaired GLP-1 signals such as CREB, PKB/Akt and S6RP in DRG of GK were restored in VG-treated group, but the effect was equivocal in diet-treated GK. Concurrently, decreased phosphorylation of insulin receptor substrate-2 (IRS2) in GK was corrected by VG-treatment. Consistent with the effect on GK, VG-treatment improved NCV in diabetic mice without influence on hyperglycemia. DRG of VG-treated diabetic mice were characterized by correction of GLP-1 signals and IRS2 phosphorylation without effects on insulin receptor-β expression. The results suggest close association of neuropathy development with impaired signaling of insulin and GLP-1 in diabetic rodents. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Left ventricular dysfunction in normotensive Type 1 diabetic patients: the impact of autonomic neuropathy

    DEFF Research Database (Denmark)

    Taskiran, M; Rasmussen, Verner; Rasmussen, Bo Valdemar

    2004-01-01

    Aims The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy (AN) are largely unknown. The aim was to determine the relative role of AN in the pathogenesis of cardiac diastolic dysfunction and left ventricular hypertrophy in Type 1...... showed a significantly greater left ventricular mass index in AN+ compared with C [103 +/- 4 g/m(2) (AN+) vs. 98 +/- 7 (AN-) and 92 +/- 4 g/m(2) (C), P hypertrophy and diastolic dysfunction in Type 1 diabetic patients...

  19. 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.

  20. Peripheral neuropathy and tear film dysfunction in type 1 diabetes mellitus.

    Science.gov (United States)

    Misra, Stuti L; Patel, Dipika V; McGhee, Charles N J; Pradhan, Monika; Kilfoyle, Dean; Braatvedt, Geoffrey D; Craig, Jennifer P

    2014-01-01

    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. 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. 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). 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.

  1. 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....

  2. 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 symptoms include imbalance when walking and ankle weakness or even foot drop, usually asymmetrical at initial presentation. The classic signs of motor neuropathy are a high medial arch, claw toes.

  3. Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

    Science.gov (United States)

    Nasiry, Davood; Khalatbary, Ali Reza; Ahmadvand, Hassan; Talebpour Amiri, Fereshteh; Akbari, Esmaeil

    2017-10-02

    Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against

  4. Intrinsic foot muscle deterioration is associated with metatarsophalangeal joint angle in people with diabetes and neuropathy.

    Science.gov (United States)

    Cheuy, Victor A; Hastings, Mary K; Commean, Paul K; Ward, Samuel R; Mueller, Michael J

    2013-01-01

    Metatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer. 23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age-matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance. The diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), Pmuscle deterioration ratio and metatarsophalangeal joint angle was r=-0.51 (P=0.01) for all diabetic, neuropathic subjects, but increased to r=-0.81 (Pmuscle deterioration ratios >1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers. Individuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown. © 2013.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Seon-Ah Cha

    Full Text Available 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.

  7. Duloxetine for the treatment of painful diabetic peripheral neuropathy in Venezuela: economic evaluation.

    Science.gov (United States)

    Carlos, Fernando; Espejel, Luis; Novick, Diego; López, Rubén; Flores, Daniel

    2015-09-25

    Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisition’s cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.

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

    Science.gov (United States)

    Ogbera, Anthonia Okeoghene; Ezeobi, Emmanuel; Unachukwu, Chioma; Oshinaike, Olajumoke

    2014-11-01

    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. 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. 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. The combination of vitamin E and Eve Primrose is beneficial in the management of mild to moderate diabetic neuropathy.

  9. Focal and multifocal diabetic neuropathies Neuropatia diabética focal e multifocal

    Directory of Open Access Journals (Sweden)

    Gérard Said

    2007-12-01

    Full Text Available Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The vast majority of the patients with clinical diabetic neuropathy have a distal symmetrical form that progress following a fiber-length dependent pattern, with predominant sensory and autonomic manifestations. This pattern of neuropathy is associated with a progressive distal axonopathy. Patients are exposed to trophic changes in the feet, pains and autonomic disturbances. Less often, diabetic patients may develop focal and multifocal neuropathy that includes cranial nerve involvement, limb and truncal neuropathies. This neuropathic pattern tends to occur after 50 years of age, mostly in patients with longstanding diabetes mellitus. The LDDP does not show any trend to improvement and either relentlessly progresses or remain relatively stable over years. Conversely the focal diabetic neuropathies, which are often associated with inflammatory vasculopathy on nerve biopsies, remain self limited, sometimes after a relapsing course.A neuropatia diabética é a mais predominante das neuropatias nos países industrializados apresentando uma gama variável de manifestações clinicas. A maioria dos pacientes com neuropatia diabética apresenta uma forma simétrica distal que progride para um padrão fibra comprimento dependente com manifestações sensitivas e autonomicas. Este tipo de neuropatia é associado com uma axonopatia distal progressiva. Os pacientes apresentam modificações tróficas nos pés, dores e distúrbios autonômicos. Menos freqüentemente os pacientes diabéticos podem desenvolver neuropatia focal e multifocal que incluem envolvimento de nervos cranianos, tronco e membros inferiores. Este padrão de neuropatia é mais freqüente em pacientes com mais de 50 anos e com longa historia de diabetes. Este tipo de neuropatia fibra-comprimento dependente não apresenta melhora, progride lentamente ou

  10. 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.

  11. 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...... 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...

  12. Vasculopathy associated with peripheral neuropathy in gait parameters of diabetic people

    Directory of Open Access Journals (Sweden)

    Alessandra Madia Mantovani

    Full Text Available Abstract Diabetic peripheral neuropathy (DPN is a common complication of diabetes mellitus when glycemic levels are poorly controlled. Sometimes DPN is accompanied by vasculopathy (DPV, which can worsen the clinical prognosis. The aim of this study was to analyze the gait parameters of nondiabetic individuals and diabetic individuals with DPN with or without DPV. METHOD The study included 68 individuals (50 to 65 years old divided into three groups: people without diabetes mellitus (n = 33, diabetic patients with DPN (n = 18, and diabetic patients with both DPN and DVP (n = 17. The participants underwent a gait evaluation using electronic baropodometry to obtain the single and double support, velocity, and pressure-time integral. RESULTS The pressure-time integral, velocity, and single support variables were lower, and the double support and double support/single support ratio were higher in the diabetic neuropathy and vasculopathy group. The velocity was lower the greater the degree of impairment of the diabetic foot. Some correlations were identified with velocity. CONCLUSION In diabetic individuals, there was a significant worsening of the gait parameters analyzed according to increasing degree of clinical impairment.

  13. Efficacy of low level laser therapy on painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Cg, Shashi Kumar; Maiya, Arun G; Hande, H Manjunath; Vidyasagar, Sudha; Rao, Karthik; Rajagopal, K V

    2015-10-02

    Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) Materials & methods: The study design is pre-post observational design. After obtaining ethical clearance and informed consent, 19 T2DM subjects were screened and confirmed for peripheral neuropathy in an outpatient setting with biochemical parameter, pain scale and Michigan Neuropathy Screening Instrument (MNSI). Low Level Laser therapy was irradiated through scanning mode with dosage of 3.1J/cm(2) on the plantar and dorsum of the foot and 3.4j/cm(2) with contact method for 10days and all subjects were reassessed at the end of the 10 day. Descriptive statistics and paired' test was used to analyze the pre-post finding within the group. Level of significance was set at pneuropathy.

  14. Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats.

    Science.gov (United States)

    Lirk, P; Verhamme, C; Boeckh, R; Stevens, M F; ten Hoope, W; Gerner, P; Blumenthal, S; de Girolami, U; van Schaik, I N; Hollmann, M W; Picardi, S

    2015-02-01

    The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s(-1) (Pneuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve block. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. [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.

  16. 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...... electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (per short-form health survey with 36 questions) were collected...

  17. Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Pritchard, Nicola; Dehghani, Cirous; Edwards, Katie; Burgin, Edward; Cheang, Nick; Kim, Hannah; Mikhaiel, Merna; Stanton, Gemma; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2015-07-01

    To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

  18. 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.

  19. Neuropathy-specific alterations in a Mexican population of diabetic patients.

    Science.gov (United States)

    Carbajal-Ramírez, Angélica; García-Macedo, Rebeca; Díaz-García, Carlos Manlio; Sanchez-Soto, Carmen; Padrón, Araceli Méndez; de la Peña, Jorge Escobedo; Cruz, Miguel; Hiriart, Marcia

    2017-08-25

    Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Our next goal was to characterize the cytokine profile (IL-6 and IL-10), nerve growth factor (NGF) and circulating cell-adhesion molecules in these patients. Finally, we aimed to compare the renal function among the groups of neuropathic patients. In a cross-sectional study, we included 217 diabetic patients classified in three groups: sensory polyneuropathy with hypoesthesia (DShP) or hyperesthesia (DSHP), and motor neuropathy (DMN). Two control groups were included: one of 26 diabetic non-neuropathic patients (DNN), and the other of 375 non-diabetic (ND) healthy subjects. The participants were attending to the Mexican Institute of Social Security. The circulating levels of NGF were significantly lower in diabetic patients, compared to healthy subjects. The range of IL-6 and IL-10 levels in neuropathic patients was higher than the control groups; however, several samples yielded null measurements. Neuropathic patients also showed increased circulating levels of the adhesion molecules ICAM, VCAM, and E-Selectin, compared to the ND group. Moreover, neuropathic patients showed reduced glomerular filtration rates compared to healthy subjects (82-103 ml/min per 1.73 m2, data as range from 25th-75th percentiles), especially in the group with DMN (45-76 ml/min per 1.73 m2). Some particular alterations in neuropathic patients included -but were not limited to- changes in circulating NGF, cell adhesion molecules, inflammation, and the worsening of the renal function. This study supports the need for further clinical surveillance and interventions considering a neuropathy-related basis.

  20. Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The fateful triangle.

    Science.gov (United States)

    Abou-El-Hassan, Hadi; Dia, Batoul; Choucair, Khalil; Eid, Stephanie A; Najdi, Farah; Baki, Lama; Talih, Farid; Eid, Assaad A; Kobeissy, Firas

    2017-10-01

    Traumatic brain injury is a detrimental medical condition particularly when accompanied by diabetes. There are several comorbidities going along with diabetes including, but not limited to, kidney failure, obesity, coronary artery disease, peripheral vascular disease, hypertension, stroke, neuropathies and amputations. Unlike diabetes type 1, diabetes type 2 is more common in adults who simultaneously suffer from other comorbid conditions making them susceptible to repetitive fall incidents and sustaining head trauma. The resulting brain insult exacerbates current psychiatric disorders such as depression and anxiety, which, in turn, increases the risk of sustaining further brain traumas. The relationship between diabetes, traumatic brain injury and psychiatric health constitutes a triad forming a non-reversible vicious cycle. At the proteomic and psychiatric levels, cellular, molecular and behavioral alterations have been reported with the induction of non-traumatic brain injury in diabetic models such as stroke. However, research into traumatic brain injury has not been systematically investigated. Thus, in cases of diabetic neuropathy complicated with traumatic brain injury, utilizing fine structural and analytical techniques allows the identification of key biological markers that can then be used as innovative diagnostics as well as novel therapeutic targets in an attempt to treat diabetes and its sequelae especially those arising from repetitive mild brain trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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).

  3. 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.

  4. 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 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.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.

    Science.gov (United States)

    Al-Mahroos, Faisal; Al-Roomi, Khaldoon

    2007-01-01

    Although epidemiological studies have persistently shown a high prevalence of diabetes in Arabs, the control of diabetes is still poor and complications of diabetes are common. We examined the prevalence of diabetic peripheral neuropathy (DN), neuropathic foot ulceration (FU) and peripheral vascular disease (PVD), and potential risk factors for these complications among patients attending primary care diabetes clinics in Bahrain. We studied 1477 diabetic patients (Type 2 diabetes 93%); to, including 635 men and 842 women, with ages ranging from 18-75 years in a cross-sectional study. The main predictor variables were demographic and clinical data, including assessment of foot and blood parameters. Mean age of the patients and duration of diabetes were 57.3 +/- 6.32 and 9.5 +/- 8.4 years, respectively. DN was present in 36.6% of the population, FU in 5.9%, and PVD in 11.8%. Diabetic patients with neuropathy were older than patients without neuropathy (P=0.001) and had had diabetes longer (P=0.002). Diabetic patients with foot ulcers had more severe neuropathy and higher vibration perception thresholds values than patients without foot ulcers (Pobesity defined by body mass index, large waist circumference, elevated triglycerides levels and hypertension but not gender, were significant risk factors for DN in both the univariate and the multivariate analyses (P< 0.05). DN and PVD also remained significant risk factors for foot ulceration in the multiple logistic regression analysis. Rates of DN and PVD are high among diabetic patients in Bahrain. Implementation of strategies for prevention, early detection, and appropriate treatment at the primary health care level are urgently needed.

  8. 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...

  9. 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.

  10. Elasticity of the tibial nerve assessed by sonoelastography was reduced before the development of neuropathy and further deterioration associated with the severity of neuropathy in patients with type 2 diabetes.

    Science.gov (United States)

    Ishibashi, Fukashi; Taniguchi, Miki; Kojima, Rie; Kawasaki, Asami; Kosaka, Aiko; Uetake, Harumi

    2016-05-01

    To measure the elasticity of the tibial nerve using sonoelastography, and to associate it with diabetic neuropathy severity, the cross-sectional area of the tibial nerve and neurophysiological findings in type 2 diabetic patients. The elasticity of the tibial nerve was measured as the tibial nerve:acoustic coupler strain ratio using high-resolution ultrasonography in 198 type 2 diabetic patients stratified into subgroups by neuropathy severity, and 29 control participants whose age and sex did not differ from the diabetic subgroups. The elasticity of the tibial nerve in patients without neuropathy (P elasticity of the tibial nerve that suggested the presence of neuropathy was 0.558. The area under the curve (0.829) was greater than that for the cross-sectional area (0.612). The cross-sectional area of the tibial nerve in diabetic patients without neuropathy (6.11 ± 0.13 mm(2)) was larger than that in controls (4.84 ± 0.16 mm(2)), and increased relative to neuropathy severity (P elasticity of the tibial nerve was negatively associated with neuropathy severity (P elasticity of the tibial nerve in type 2 diabetic patients could reveal early biomechanical changes that were likely caused by thickened fibrous sheaths of peripheral nerves, and might be a novel tool for characterizing diabetic neuropathy.

  11. Serum levels of TGF-β1 in patients of diabetic peripheral neuropathy and its correlation with nerve conduction velocity in type 2 diabetes mellitus.

    Science.gov (United States)

    Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

    2016-01-01

    To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. Effects of diabetes mellitus type Ι with or without neuropathy on vestibular evoked myogenic potentials.

    Science.gov (United States)

    Kamali, Behnoush; Hajiabolhassan, Fahimeh; Fatahi, Jamileh; Nasli Esfahani, Ensieh; Sarrafzadeh, Javad; Faghihzadeh, Soghrat

    2013-03-16

    Diabetes mellitus type Ι is a metabolic disorder that affects multiple systems including the inner ear. Patients with diabetes mellitus commonly complain about dizziness, floating sensation, tinnitus and sweating. The aim of this study was to compare vestibular evoked myogenic potentials (VEMPs) between diabetic patients with or without neuropathy. Subjects included 14 patients with diabetes mellitus type Ι with polyneuropathy, 10 patients with diabetes mellitus type Ι without polyneuropathy and 24 healthy volunteers. Range of age in participants was 15-40 years old. The VEMPs were recorded with 500 Hz tone bursts with intensity at 95 dB. There was statistically significant difference between the groups in P13 and N23 latencies (P<0.05). There was no statistically significant difference between groups in absolute and relative amplitudes. Prolonged latencies of the VEMP suggest lesions in the retrolabyrinthine, especially in the vestibulospinal tract.

  13. Effects of Diabetes Mellitus Type Ι with or without Neuropathy on Vestibular Evoked Myogenic Potentials

    Directory of Open Access Journals (Sweden)

    Behnoush Kamali

    2013-02-01

    Full Text Available Diabetes mellitus type Ι is a metabolic disorder that affects multiple systems including the inner ear. Patients with diabetes mellitus commonly complain about dizziness, floating sensation, tinnitus and sweating. The aim of this study was to compare vestibular evoked myogenic potentials (VEMPs between diabetic patients with or without neuropathy. Subjects included 14 patients with diabetes mellitus type Ι with polyneuropathy, 10 patients with diabetes mellitus type Ι without polyneuropathy and 24 healthy volunteers. Range of age in participants was 15-40 years old. The VEMPs were recorded with 500 Hz tone bursts with intensity at 95 dB. There was statistically significant difference between the groups in P13 and N23 latencies (P<0.05. There was no statistically significant difference between groups in absolute and relative amplitudes. Prolonged latencies of the VEMP suggest lesions in the retrolabyrinthine, especially in the vestibulospinal tract.

  14. 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.

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

    Science.gov (United States)

    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

    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. Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal. We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro. These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue. © The Author(s) 2016.

  16. Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion

    Science.gov (United States)

    Terashima, Tomoya; Kojima, Hideto; Chan, Lawrence

    2012-01-01

    Diabetic neuropathy is the most common diabetic complication. The pathogenetic pathways include oxidative stress, advanced glycation end product (AGE) formation, protein kinase C, and NF-κB activation, as well as increased polyol flux. These metabolic perturbations affect neurons, Schwann cells, and vasa nervorum, which are held to be the primary cell types involved. We hypothesize that diabetes induces the appearance of abnormal bone marrow-derived cells (BMDCs) that fuse with neurons in the dorsal root ganglia (DRG) of mice, leading to diabetic neuropathy. Neuronal poly(ADP-ribose) polymerase-1 (PARP-1) activation in diabetes is known to generate free radical and oxidant-induced injury and poly(ADP-ribose) polymer formation, resulting in neuronal death and dysfunction, culminating in neuropathy. We further hypothesize that BM-specific PARP expression plays a determining role in disease pathogenesis. Here we show that bone marrow transplantation (BMT) of PARP-knockout (PARPKO) cells to wild-type mice protects against, whereas BMT of wild-type cells to PARPKO mice, which are normally “neuropathy-resistant,” confers susceptibility to, diabetic neuropathy. The pathogenetic process involving hyperglycemia, BMDCs, and BMDC-neuron fusion can be recapitulated in vitro. Incubation in high, but not low, glucose confers fusogenicity to BMDCs, which are characterized by proinsulin (PI) and TNF-α coexpression; coincubation of isolated DRG neurons with PI-BMDCs in high glucose leads to spontaneous fusion between the 2 cell types, while the presence of a PARP inhibitor or use of PARPKO BMDCs in the incubation protects against BMDC-neuron fusion. These complementary in vivo and in vitro experiments indicate that BMDC-PARP expression promotes diabetic neuropathy via BMDC-neuron fusion.—Terashima, T., Kojima, H., Chan, L. Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion. PMID:21978940

  17. Comparative role of pregabalin and carbamazepine regarding efficacy in painful diabetic neuropathy.

    Science.gov (United States)

    Mahmood, Raana; Jawed, Itrat; Khan, M Irfan; Mahmood, Iffat; Tariq, Talat; Kamil, Arfa; Sayeed, Faiza Z; Sayeed, Bushra Z

    2017-07-01

    Neuropathic pain is the most severe and resistant type of pain which has impact on quality of life and behaviour; it most commonly occurs at night causing disturbed sleep. Diabetes mellitus is a common cause of painful neuropathy. In this study, we are comparing the effectiveness of old treatment Carbamazepine with Pregabalin in painful diabetic neuropathy. The study was an open-label trial conducted in Diabetic Clinic of Medical Unit-III, Jinnah Post-graduate Medical Center, Karachi. The duration of the study was 90 days, from December 2010 to March 2011. The study has been approved from ethical committee of JPMC, Karachi with the reference NO.F.2-81/2010-GENL/195/JPMC. 60 established patients of painful diabetic peripheral neuropathy from Diabetic Clinic of Medical Unit-III OPD were included in the 90-day study, irrespective of gender, with duration of diabetes more than 10 years. All subjects are placed into two groups. In group A, comprising of 30 patients (n=30), Pregabalin was administered and in group B, also comprising of 30 patients (n=30), Carbamazepine. The intensity of pain was compared on visual analog scale of McGill pain questionnaire. In group A (Pregabalin), the mean pain score fell from 6.17±0.14 to 3.50±0.15 from day 0 to day 90 (p-value=0.001) and the percentage of change also in visual analog scale of McGill pain questionnaire was -43.31%. In group B (Carbamazepine), the changes in pain score from initially 6.07±0.14 falling to 4.23±0.13 from day 0 to day 90 (p-value=0.001) and the percentage of change was -30.31%. Pregabalin was observed to be more potent. Both drugs were well tolerated by all participants that also completed the entire duration of the trial.

  18. Clinical correlates of painful diabetic neuropathy and relationship of neuropathic pain with sensorimotor and autonomic nerve function.

    Science.gov (United States)

    Spallone, Vincenza; Morganti, Roberto; D'Amato, Cinzia; Cacciotti, Laura; Fedele, Tiziana; Maiello, Maria R; Marfia, Girolama

    2011-02-01

    This study investigated the clinical correlates of painful diabetic polyneuropathy (PDPN) and the relationship of neuropathic pain with sensorimotor and autonomic nerve function. Seventy-eight diabetic patients with PDPN (PDPN(+)), 57 with non-painful diabetic polyneuropathy (DPN(+)), and 56 without diabetic polyneuropathy (DPN(-)) were prospectively studied. Autonomic neuropathy, neuropathic symptoms and signs, vibration perception threshold, and neuropathic pain were assessed using 4 cardiovascular tests, scoring systems for symptoms and signs (Michigan Diabetic Neuropathy Score, MDNS), Biothesiometer, and a numerical rating scale. Compared to DPN(+), PDPN(+) patients displayed higher BMI (P=0.0043), waist circumference (P=0.0057), neuropathy symptom score (Pbody mass index (BMI), abdominal obesity, diabetes type, diabetes duration, HbA1c, blood pressure, triglycerides, smoking, peripheral arterial disease, Valsalva ratio and MDNS as the independent variables, BMI (OR 1.22, P=0.0012) and MDNS (OR 1.27, P=0.0005) were significantly and independently associated with PDPN. In a multivariate regression analysis including as independent variables also sex, age, diabetes type, diabetes duration and Valsalva ratio, 24-h pain score was significantly related to neuropathy symptom score (P=0.0011), MDNS (P=0.0158), and 10g monofilament (P=0.018). BMI and sensorimotor deficits were the main determinants of PDPN and, as a novel finding, neuropathic pain intensity was related to the degree of neuropathy deficits. Thus, some peculiarity exists in metabolic correlates of diabetic neuropathic pain compared to insensate neuropathy but painfulness can still coexist with insensitivity. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  19. 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

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

    Science.gov (United States)

    Usuki, Seigo; Ito, Yukihiko; Morikawa, Keiko; Kise, Mitsuo; Ariga, Toshio; Rivner, Michael; Yu, Robert K

    2007-11-23

    To study the effects of a pre-germinated brown rice diet (PR) on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. 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. Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher, respectively), and increased Na+/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 < 0.001). The 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). 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

  1. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

    Directory of Open Access Journals (Sweden)

    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.

  2. Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes after Vitamin D Supplementation

    Directory of Open Access Journals (Sweden)

    Uazman Alam

    2017-01-01

    Full Text Available Objective. To assess the effect of vitamin D supplementation on neuropathy specific quality of life (NeuroQoL in patients with painful diabetic neuropathy. Methods. This prospective, open label study was conducted between June 2012 and April 2013. Patients with symptomatic diabetic neuropathy were given a single dose of 600,000 IU intramuscular vitamin D, and NeuroQol was assessed at baseline and at five follow-up visits every 4 weeks. Results. Of 143 participants, 41.3% were vitamin D deficient (vitamin D < 20 ng/ml. Treatment with vitamin D resulted in a significant increase in 25(OHD (P<0.0001 and a significant improvement in the NeuroQoL subscale score for emotional distress (P=0.04, with no significant change in the other NeuroQoL domains of painful symptoms and paresthesia, loss of temperature and touch sensation, unsteadiness, limitation in daily activities, and interpersonal problems. There was a significant reduction in patient perception about foot problems on QoL of “quite a lot” (P<0.05 and “very much” (P<0.0001 with a significant reduction in the baseline response of having a “poor” QoL from 5.2% to 0.7% (P<0.0001 and an increase in the response of an “excellent QoL” from 1.5% to 7.4% (P<0.0001. Conclusion. Vitamin D is effective in improving quality of life in patients with painful diabetic neuropathy.

  3. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy.

    Science.gov (United States)

    Kessler, John A; Smith, A Gordon; Cha, Bong-Soo; Choi, Sung Hee; Wymer, James; Shaibani, Aziz; Ajroud-Driss, Senda; Vinik, Aaron

    2015-05-01

    To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin.

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

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    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.

  5. The Preferential Impairment of Pupil Constriction Stimulated by Blue Light in Patients with Type 2 Diabetes without Autonomic Neuropathy

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    Fukashi Ishibashi

    2017-01-01

    Full Text Available The main aim of the present paper is to examine whether the pupillary light reflex (PLR mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs is impaired in type 2 diabetic patients. One hundred and three diabetic patients without diabetic autonomic neuropathy (DAN and 42 age-matched controls underwent a series of detailed neurological examinations. The patients were stratified into three groups: stage I, no neuropathy; stage II, asymptomatic neuropathy; stage III, symptomatic but without DAN. The PLR to 470 and 635 nm light at 20 cd/m2 was recorded. Small fiber neuropathy was assessed by corneal confocal microscopy and quantifying corneal nerve fiber (CNF morphology. The 470 nm light induced a stronger and faster PLR than did 635 nm light in all subjects. The PLR to both lights was impaired equally across all of the diabetic subgroups. The postillumination pupil response (PIPR after 470 nm light offset at ≥1.7 sec was attenuated in diabetic patients without differences between subgroups. Receiver operating characteristic analysis revealed that the PIPR mediated by ipRGCs in patients with stage II and stage III neuropathy was different from that of the control subjects. Clinical factors, nerve conduction velocity, and CNF measures were significantly correlated with PLR parameters with 470 nm light. PLR kinetics were more impaired by stimulation with blue light than with red light in diabetic patients without DAN.

  6. Associations of serum anti-ganglioside antibodies and inflammatory markers in diabetic peripheral neuropathy.

    Science.gov (United States)

    Ge, Shengjie; Xie, Jing; Zheng, Lequn; Yang, Lijuan; Zhu, Hong; Cheng, Xingbo; Shen, Feixia

    2016-05-01

    To investigate the associations between inflammatory markers, serum anti-ganglioside antibodies (anti-GS-ab), serum plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and diabetic peripheral neuropathy (DPN). Study subjects were divided into three groups: normal group (N group) with 101 healthy individuals; diabetes mellitus without peripheral neuropathy group (DM group) with 87 patients; and DPN group with 178 cases. American Nicolet Viking IV electromyography was applied to detect nerve conduction velocity; enzyme linked immunosorbent assay was used to determine the levels of anti-GS-IgG-ab, PAI-1, and TNF-α; and immunoturbidimetry was employed to measure CRP levels. Motor nerve conduction velocity and sensory nerve conduction velocity in the DNC group were significantly lower than in the N and DM groups (all Pdiabetic peripheral neuropathy clinical (DPNC) levels were statistically significant (Panti-GS-ab was positively correlated with DPNC. There were statistically significant differences in PAI-1, TNF-α, and CRP levels between the DPN group and DM and N groups (both P0.05), and the concentration of anti-GS-IgM-ab was in significant positive correlated with PAI-1, TNF-α, and CRP levels. Anti-GS-ab and inflammatory markers such as PAI-1, TNF-α, and CRP were associated with DPN and can be used as important indicators for the prediction and early diagnosis of DPN. Copyright © 2016. Published by Elsevier Ireland Ltd.

  7. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.

    Science.gov (United States)

    Gupta, Kamesh; Jain, Anand; Rohatgi, Anurag

    2017-08-25

    A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12B12 deficiency as B12 levels(r=-0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. Lack of Definite Association of Vitamin D Deficiency with Diabetic Neuropathy. Investigation in Greek and in Bangladeshi Patients

    Science.gov (United States)

    ZAMBELIS, THOMAS; PAPADAKIS, GEORGE; KOKOTIS, PANAGIOTIS; VILLIOTOU, VASSILIKI; DOGKAS, NIKOLAOS; KARANDREAS, NIKOLAOS

    2017-01-01

    Aim: Determination of the 25(OH) vitamin D levels in Greek-born and in Bangladeshi immigrant patients in Greece with diabetes with and without polyneuropathy. Materials and Methods: The method for the detection and staging of polyneuropathy proposed by Dyck, 1988 was used. Results: A total of 111 Bangladeshi immigrants and 101 Greek diabetic patients took part in the study. Vitamin D levels were significantly lower in Bangladeshi than in Greek diabetic patients, and were significantly lower in Greek patients with small-fiber neuropathy. In Bangladeshi patients, there was no statistically significant difference in the subgroup of patients with polyneuropathy in comparison to those without polyneuropathy. Conclusion: The association of vitamin D deficiency only with a small number of Greek patients with exclusively small-fiber neuropathy does not allow us to draw a definite conclusion on the role of vitamin D in the pathogenesis of diabetic neuropathy. PMID:28358709

  9. 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

  10. Offloading effect of therapeutic footwear in patients with diabetic neuropathy at high risk for plantar foot ulceration

    NARCIS (Netherlands)

    Arts, M. L. J.; Waaijman, R.; de Haart, M.; Keukenkamp, R.; Nollet, F.; Bus, S. A.

    2012-01-01

    Diabet. Med. 29, 15341541 (2012) Abstract Aims Custom-made therapeutic footwear is often prescribed to patients with diabetic neuropathy, foot deformity and a healed plantar foot ulcer. Offloading these feet is important to prevent ulcer recurrence. The aim was to evaluate the offloading effect of

  11. Cardiovascular autonomic neuropathy in non-diabetic Nigerian ...

    African Journals Online (AJOL)

    , its pattern and clinical predictors in Nigerians with non-diabetic chronic renal failure (CRF) Methods: A total of 120 subjects comprising 60 pre-dialysis CRF patients and an equal number of age- and sex - matched healthy controls were ...

  12. Screening For Peripheral Neuropathy In Diabetic Patients: The ...

    African Journals Online (AJOL)

    Background: Peripheral nerve damage is a common complication of diabetes mellitus and often presents with a gamut of unpleasant sensations difficult to assess accurately clinically. Objective: To describe the United Kingdom Screening Test (UKST), a simple, accurate and reproducible clinical method for assessing the ...

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

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    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.

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

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    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.

  15. 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.

  16. 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.

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

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    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.

  18. 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.

  19. An improved experimental model for peripheral neuropathy in rats

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    Q.M. Dias

    Full Text Available A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively, but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively. The modified method required less surgical skill than the spinal nerve ligation model.

  20. An improved experimental model for peripheral neuropathy in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Q.M.; Rossaneis, A.C.; Fais, R.S.; Prado, W.A. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-03-15

    A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

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

    Science.gov (United States)

    Yi, Liu Chiao; Sartor, Cristina D; Souza, Francis Trombini; Sacco, Isabel C N

    2016-01-01

    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 swing.

  2. 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

  3. Diabetic peripheral neuropathy and its evaluation in a clinical scenario: A review

    Directory of Open Access Journals (Sweden)

    S Dixit

    2014-01-01

    Full Text Available Diabetes mellitus is not only a clinical syndrome characterizing hyperglycemia, but is also a cause of debilitating problem known as peripheral neuropathy (PN. This review addresses the importance of diagnosing PN in a clinical setting as PN causes pain and discomfort in lower extremities, loss or absence of protective sensations in the lower extremities leading to balance problems, risk of foot ulcerations, and a reduced quality of life in adults with type 2 diabetes. A variety of modalities or methods are available to evaluate both subjective and objective measures of peripheral nerve functions, and have been discussed in detail in this review. It is of utmost importance to understand that evaluating PN as a routine practice in a simple way may also play a vitally important role in preventing foot ulcers or fall-related morbidity and mortality in adults with type 2 diabetes.

  4. In Vivo Confocal Microscopy of Corneal Nerves: An Ocular Biomarker for Peripheral and Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Misra, Stuti L; Craig, Jennifer P; Patel, Dipika V; McGhee, Charles N J; Pradhan, Monika; Ellyett, Kevin; Kilfoyle, Dean; Braatvedt, Geoffrey D

    2015-08-01

    We investigated the relationship between corneal subbasal nerve (SBN) plexus density, corneal sensitivity, and peripheral and cardiac autonomic neuropathy in patients with type 1 diabetes mellitus. We recruited 53 patients with type 1 diabetes mellitus and 40 normal control participants. Corneal in vivo confocal microscopy (IVCM) and sensitivity testing were performed on one eye of each subject. Autonomic function testing was done and an overall neuropathy score obtained from a combination of a symptomatic neuropathy score, clinical assessment, biothesiometry, and nerve conduction tests. The corneal SBN density (P < 0.001) and corneal sensitivity (P < 0.001) were significantly lower in subjects with diabetes compared to controls. A modest negative correlation between total neuropathy score and SBN density was observed (r = -0.33, P = 0.01). A negative correlation between corneal sensitivity and expiration/inspiration component of the autonomic nerve analysis (ANS-EI) also was noted (r = -0.36, P = 0.008). Corneal SBN density was abnormal in 50% of diabetic subjects classified as "Normal" by the clinical and electrophysiological based tests of total neuropathy score. The correlation of corneal SBN density with total neuropathy score suggests that reduced corneal nerve density reflects peripheral neuropathy in diabetes. Corneal SBN changes precede other clinical and electrophysiology tests of neuropathy supporting a possible role for corneal IVCM and corneal sensitivity testing as surrogate markers in the assessment of diabetic peripheral and cardiac autonomic neuropathy.

  5. Comparison of shoe-length fit between people with and without diabetic peripheral neuropathy: a case–control study

    Directory of Open Access Journals (Sweden)

    McInnes Alistair D

    2012-04-01

    Full Text Available Abstract Background Amongst the many identified mechanisms leading to diabetic foot ulceration, ill-fitting footwear is one. There is anecdotal evidence that people with diabetic peripheral neuropathy wear shoes that are too small in order to increase the sensation of fit. The aim of this study was to determine whether people with diabetic sensory neuropathy wear appropriate length footwear. Methods A case–control design was used to compare internal shoe length and foot length differences between a group of people with diabetes and peripheral sensory neuropathy and a group of people without diabetes and no peripheral sensory neuropathy. Shoe and foot length measurements were taken using a calibrated Internal Shoe Size Gauge® and a Brannock Device®, respectively. Results Data was collected from 85 participants with diabetes and 118 participants without diabetes. The mean difference between shoe and foot length was not significantly different between the two groups. However, a significant number of participants within both groups had a shoe to foot length difference that lay outside a previously suggested 10 to 15 mm range. From the diabetic and non-diabetic groups 82% (70/85 and 66% (78/118, respectively had a foot to shoe length difference outside this same range. Conclusions This study shows that although there is no significant difference in shoe-length fit between participants with and without neuropathy, a significant proportion of these populations wear shoes that are either too long or too short for their foot length according to the 10 to 15 mm value used for comparison. The study has highlighted the need for standardised approaches when considering the allowance required between foot and internal shoe length and for the measurement and comparison of foot and shoe dimensions.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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).

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

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    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. The Effect of Eight weeks of Resistance Training on Static and Dynamic Balance as Well as Power of the Foot Muscles in Diabetic Women with Peripheral Neuropathy

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    A Hedayati

    2015-12-01

    Full Text Available Introduction: Diabetic peripheral neuropathy, due to involvement of the peripheral nerves, causes muscle weakness and loss of balance in the lower extremities. Therefore, this study aimed to evaluate the effect of resistance exercise on balance and  muscle strength of lower extremities in women with diabetes who suffered from peripheral neuropathy. Methods: The study population consisted of 700 diabetic patients, referring to diabetes clinic in Mashhad, Iran, out of which  20 neuropathic diabetic patients were  selected and nonrandomly divided into one treatment group(n=10 and one control (n = 10 group. Static and dynamic balance were measured by the Biodex Balance and strength of the quadriceps muscles and twins were measured by the dynamometer before and after the intervention. Resistance exercise were performed three times a week for two months which, each session lasted an hour with intensity of 30 - 50% 1RM (first meeting was held with 10 repetitions and then, it was increased to 15 repetitions. SPSS statistical analysis software was applied using t-test in order to statiscally analyze the study data and the significance level was set at p &le0/05. Results: Static and dynamic balance as well as quadriceps muscle strength increased significantly in the experimental group. While the twin muscles in the control group showed a significant change (0/05&gep, no significant difference was observed in the other variables (0/05 diabetic women (suffering from peripheral neuropathy increases muscle strength and balance.

  10. The Need for Improved Management of Painful Diabetic Neuropathy in Primary Care

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    Teresa Sobhy

    2016-01-01

    Full Text Available The provision of care for patients with type II diabetes in primary care must involve assessing patients for peripheral neuropathy of the feet. Objectives. This paper will demonstrate that painful diabetic neuropathy (PDN is poorly assessed for and treated in primary care. Methods. A critical analysis of research will be conducted to identify the prevalence and impact of PDN among individuals with type II diabetes. Results. Research evidence and best practice guidelines are widely available in supporting primary care practitioners to better assess for and treat PDN. However, the lack of knowledge, awareness, and implementation of such research and guidelines prevents patients with PDN from receiving appropriate care. Discussion. Much international research exists on the prevalence and impact of PDN in primary care; however, Canadian research is lacking. Furthermore, the quantity and quality of research on treatment modalities for PDN are inadequate. Finally, current research and guidelines on PDN management are inadequately implemented in the clinical setting. Conclusion. The undertreatment of PDN has significant implications on the individual, family, and society. Healthcare practitioners must be more aware of and better implement current research and guidelines into practice to resolve this clinical issue.

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

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    Castany, Sílvia; Carcolé, Mireia; Leánez, Sergi; Pol, Olga

    2016-01-01

    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 CoPP alone or

  12. 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

  13. Peripheral Neuropathy

    Science.gov (United States)

    ... exposure to toxins. One of the most common causes is diabetes mellitus. People with peripheral neuropathy generally describe the ... thyroid (hypothyroidism). In a number of cases, no cause can be identified ... include: Diabetes mellitus, especially if your sugar levels are poorly ...

  14. Up-regulation of the receptor for advanced glycation end products in the skin biopsy specimens of patients with severe diabetic neuropathy.

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    Park, Su-Yeon; Kim, Young-A; Hong, Yoon-Ho; Moon, Min-Kyong; Koo, Bo-Kyeong; Kim, Tae Wan

    2014-10-01

    The receptor for advanced glycation end products (RAGE) may contribute to the development of diabetic neuropathy. To assess its relevance in humans, this study examined the expression of RAGE in the skin biopsy samples of patients with diabetes mellitus, and investigated its correlation with intraepidermal nerve-fiber density (IENFD) and clinical measures of neuropathy severity. Forty-four patients who either had type 2 diabetes or were prediabetes underwent clinical evaluation and a 3-mm skin punch biopsy. The clinical severity of their neuropathy was assessed using the Michigan Diabetic Neuropathy Score. IENFD was measured along with immunohistochemical staining for RAGE in 29 skin biopsy samples. The expression of RAGE was also quantified by real-time reverse-transcription PCR in the remaining 15 patients. RAGE was localized mostly in the dermal and subcutaneous vascular endothelia. The staining was more intense in patients with a lower IENFD (p=0.004). The quantity of RAGE mRNA was significantly higher in patients with severe neuropathy than in those with no or mild neuropathy (p=0.003). The up-regulation of RAGE was related to dyslipidemia and diabetic nephropathy. There was a trend toward decreased sural nerve action-potential amplitude and slowed peroneal motor-nerve conduction with increasing RAGE expression. The findings of this study demonstrate up-regulation of RAGE in skin biopsy samples from patients with diabetic neuropathy, supporting a pathogenic role of RAGE in the development of diabetic neuropathy.

  15. Prevalence, severity and factors associated with peripheral neuropathy among newly diagnosed diabetic patients attending Mulago hospital: a cross-sectional study.

    Science.gov (United States)

    Kisozi, Twaha; Mutebi, Edris; Kisekka, Musubire; Lhatoo, Samden; Sajatovic, Martha; Kaddumukasa, Mark; Nakwagala, Fredrick Nelson; Katabira, Elly

    2017-06-01

    To determine the prevalence and associated risk factors of diabetic peripheral neuropathy (DPN) among newly diagnosed diabetes mellitus patients in Mulago Hospital. A cross-sectional study was conducted among 248 newly diagnosed adult diabetic patients. Using the standard Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria, we screened them for neuropathy. Data on the socio-demographics, age, duration of symptoms and history of diabetic ulcer were analyzed using a multiple logistic regression. A p-value neuropathy and only five percent had severe neuropathy. Age above 60 years was significantly associated with the presence of DPN; (OR 3.72; 95% CI 1.25 - 11.03; p=0.018). The history of ever having a foot ulcer was significantly associated with peripheral neuropathy (OR 2.59; 95% CI: 1.03 - 6.49, p = 0.042). DPN occurs in 1 in 4 of newly diagnosed diabetic patients in Mulago hospital. Two thirds of these patients had moderate to severe neuropathy. DPN was independently associated with increasing age. Early diagnosis of diabetes mellitus, increased diabetes knowledge and regular blood sugar screenings would play an important role in identifying this problem.

  16. Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure.

    Science.gov (United States)

    Fernando, Malindu; Crowther, Robert; Lazzarini, Peter; Sangla, Kunwarjit; Cunningham, Margaret; Buttner, Petra; Golledge, Jonathan

    2013-10-01

    Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes. Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. © 2013.

  17. 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

  18. 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 < 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. 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.

  19. 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.

  20. Peripheral neuropathy as a complication of diabetic ketoacidosis in a child with newly diagnosed diabetes type 1 - case report.

    Science.gov (United States)

    Baszyńska-Wilk, Marta; Wysocka-Mincewicz, Marta; Świercz, Anna; Świderska, Jolanta; Marszał, Magdalena; Szalecki, Mieczysław

    2017-12-08

    Neurological complications of diabetic ketoacidosis are considered to be very serious clinical problem. The most common complication is cerebral edema. However this group includes also less common syndromes such as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or very rare peripheral neuropathy. We present a case of 9-year old girl with new onset type 1 diabetes, diabetic ketoacidosis, cerebral edema, multifocal vasogenic brain lesions and lower limbs peripheral paresis. The patient developed polydipsia and polyuria one week before admission to the hospital. In laboratory tests initial blood glucose level 1136 mg/dl and acidosis (pH 7.1; BE-25.9) were noted. She was admitted to the hospital in a critical condition and required treatment in intensive care unit. Computed tomography scan showed brain edema and hipodense lesion in the left temporal region. Brain MRI revealed more advanced multifocal brain lesions Nerve conduction studies demonstrated damage of the motor neuron in both lower extremities with dysfunction in both peroneal nerves and the right tibial nerve. As a result of diabetological, neurological treatment and physiotherapy patient's health state gradually improved. Acute neuropathy after ketoacidosis is rare complication and its pathomechanism is not clear. Patients with DKA require careful monitoring of neurological functions even after normalization of glycemic parameters.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  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. CARDIAC AUTONOMIC NEUROPATHY AND MICROALBUMINURIA IN TYPE 2 DIABETES MELLITUS- A CROSS-SECTIONAL ANALYSIS

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    Suresh Padmini

    2017-02-01

    Full Text Available BACKGROUND Autonomous neuropathy is one of the least focused complications of type 2 diabetes mellitus in clinical practice. CAN is a significant cause of morbidity and mortality associated with a high risk of cardiac arrhythmias and sudden death. Higher urinary albumin excretion has been suggested as a predicting diabetic nephropathy. This cross-sectional study sought to determine relationship of CAN with early renal decline in type 2 diabetes mellitus. MATERIALS AND METHODS Over a period of two years, patients with type 2 diabetes mellitus after careful exclusion of other risk factors for proteinuria, 199 patients were included in this cross-sectional survey. CAN was measured by portable ANSiscope and 24-hour urine microalbumin level was estimated. Correlation was sought between the two variable. RESULTS Out of the 199 patients chosen for the study, 127 were male. The mean age of diabetes was 6.4±3.9 years. 57.8% had late or advanced CAN and there was a significant linear correlation with 24-hour urine microalbumin levels. CONCLUSION Measurement of CAN is an effective way to assess the level of cardiac sympathetic dysfunction due to disease in patients with type 2 diabetes mellitus of more than 5 years duration. Urine microalbumin levels correlate with the degree of CAN. There is a strong need to conduct more studies about CAN to fully understand its pathology and develop treatment strategies to reduce cardiac mortality.

  4. Evaluation of olfaction and taste function in type 2 diabetic patients with and without peripheral neuropathy.

    Science.gov (United States)

    Yazla, Semih; Özmen, Süay; Kıyıcı, Sinem; Yıldız, Demet; Haksever, Mehmet; Gencay, Sündüz

    2017-12-12

    Olfaction and gustation in patients with diabetes mellitus have great significance on quality of life, and their impairment may result in possible hazards. A limited number of studies have been performed to determine the alteration of both gustatory and olfactory function in type 2 diabetic patients with diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether type 2 diabetic patients, with and without DPN, exhibit major olfactory and gustatory dysfunction using validated and dependable techniques. An observational-analytical case-control study was conducted. Sixty patients with type 2 diabetes mellitus (T2DM) and 30 healthy control subjects with a mean age of 57.1 ± 8.4 were included in the study. Patients with T2DM were recruited from the endocrinology outpatient clinic. After clinical evaluation and electromyography examination, patients with T2DM were divided into the 2 groups, with and without DPN. After a 10-hour fasting period, blood samples were taken for the measurement of serum creatinine, lipids, and HbA1c. For the quantitative assessment of olfactory function, all participants underwent butanol threshold test and odour identification test. Gustatory function was tested administering a whole-mouth above-threshold test using sucrose solutions. The control subjects showed significantly higher Sniffin' sticks and butanol threshold scores than the diabetic patients without DPN (P = .001 and P = .009). No significant difference was found in the gustatory function test between these 2 groups (P = .116). Diabetic patients with DPN had lower Sniffin' sticks scores, butanol threshold scores, and higher sucrose thresholds compared to the controls (P diabetic patients with or without DPN regarding Sniffin' sticks scores, butanol threshold, and sucrose thresholds (P = .302, P = .181, and P = .118). In conclusion, this study demonstrates that T2DM is associated with olfactory and gustatory dysfunction. The fact that there

  5. 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

  6. 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

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

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    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%: pgait alterations in people with clinically severe peripheral neuropathy and related plantar foot ulcer history. Further research is needed to explore potential casual pathways. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 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.

  9. Effects of Icariside II on corpus cavernosum and major pelvic ganglion neuropathy in streptozotocin-induced diabetic rats.

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    Bai, Guang-Yi; Zhou, Feng; Hui, Yu; Xu, Yong-De; Lei, Hong-En; Pu, Jin-Xian; Xin, Zhong-Cheng

    2014-12-15

    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.

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

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    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, Pdiabetes (rPearson = 0.58-071, 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.

  11. [The relationship between sleep quality and diabetic autonomic neuropathy in elder patients with type 2 diabetes mellitus].

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    Zhang, Jie; Zhang, Lina; Guo, Lixin

    2016-03-01

    To explore the relationship between the sleep quality and diabetic autonomic neuropathy of elder patients with type 2 diabetes mellitus. A total of 90 elder patients with diabetes in Beijing Hospital was enrolled in this study. Questionnaires of Pittsburgh Sleep Quality Index(PSQI) were completed to evaluate the quality of sleep and Holter was applied to evaluate heart rate variability (HRV). Other related clinical data such as, catecholamine[epinephrine(E); norepinephrine(NE); dopamine(DA)]and diabetes complications were also collected after admission to the hospital. Patients were divided into three groups: the poor-sleeper group, the common-sleeper group and the good-sleeper group according to PSQI score. HRV and the level of catecholamine were compared among three groups. The level of HRV including meanNN [(743 ± 58) ms vs(824 ± 99)ms and (837 ± 104)ms], ASDNN [(30 ± 10)ms vs (39 ± 14)ms and (41 ± 14)ms], very low frequency(VLF)[(15.33 ± 6.10)ms(2) vs(22.11 ± 7.94)ms(2) and (22.66 ± 7.87)ms(2)], low frequency (LF)[(8.30 ± 3.95) ms(2) vs(12.58 ± 6.11)ms(2) and(12.81 ± 6.96)ms(2)] and LF/high frequency(HF)[(1.23 ± 0.32) vs (1.56 ± 0.46) and (1.47 ± 0.42)] in the poor-sleeper group were lower than in both the common-sleeper group and good-sleeper group (all Ppoor-sleeper group [E: (108.91 ± 4.19)ng/L; NE: (1458.0 ± 50.35)ng/L] were lower than both the common-sleeper group [E: (120.23 ± 4.37) ng/L; NE: (1901.09 ± 131.36)ng/L] and the good-sleeper group [E: (118.23 ± 19.9)ng/L; NE: (1771.87 ± 116.73)ng/L] (all Ppoor-sleeper group. Sleep quality is associated with the severity of diabetic autonomic neuropathy and might be one of clinical features for diabetic autonomic neuropathy.

  12. 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.

  13. Footboards: Indigenous and novel method of screening for diabetes peripheral neuropathy – A pilot study

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    Akram Hussain Bijli

    2017-01-01

    Full Text Available Background: To validate the effectiveness of indigenously designed “footboard (FB” in early diagnosis of diabetic peripheral neuropathy (PNP by comparing it with Semmes–Weinstein monofilament (SWM and vibration perception (VP. Materials and Methods: Two hundred and forty-four patients with diabetes were examined for PNP using SWM and 128 Hz tuning fork. The findings were compared with indigenously designed FBs with 1, 2, and 3 mm elevations. Results: Out of 108 patients who did not have protective sensation as per SWM, only 10 (9.2% felt 1 mm board bearings, and out of 72 patients who did not feel vibration, only 8 (11.1% felt 1 mm board bearings. Out of 136 patients who had protective sensation, 128 (94.11% felt 2 mm elevated board bearings, and out of 172 patients who had VP, only 152 patients (88.3% felt 2 mm board bearings. With SWM as standard, the sensitivities and specificities, respectively, were 63% and 90% (1 mm board, and 94% and 60% (2 mm board. With VP, the sensitivities and specificities, respectively, were 59% and 90% (1 mm board, and 88% and 61% (2 mm board. Conclusions: FB, which simultaneously tests touch and pressure sensation, shows a high level of performance in detecting at-risk feet. FB may be simple, time-efficient, and inexpensive test for detection of neuropathy and needs further validation in a larger study.

  14. 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

  15. Electrotherapy for the treatment of painful diabetic peripheral neuropathy: a review.

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    Pieber, Karin; Herceg, Malvina; Paternostro-Sluga, Tatjana

    2010-04-01

    To review different types of electrotherapy for the treatment of painful diabetic peripheral neuropathy. A structured search of the electronic database MEDLINE was performed from the time of its initiation to July 2009. Articles in English and German were selected. The efficacy of different types of electrotherapy for painful diabetic peripheral neuropathy has been evaluated in 15 studies; the effects of transcutaneous electrical nerve stimulation are consistent. The beneficial effects of prolonged use have been reported in three large studies and one small study. The effects of frequency-modulated electromagnetic neural stimulation were assessed in one large study, and a significant reduction in pain was reported. Treatment with pulsed and static electromagnetic fields has been investigated in two small and three large studies, and analgesic benefits have been reported. In one large study focusing on pulsed electromagnetic fields, no beneficial effect on pain was registered. Only small studies were found concerning other types of electrotherapy, such as pulsed-dose electrical stimulation, high-frequency external muscle stimulation or high-tone external muscle stimulation. The conclusions drawn in these articles are diverse. Shortcomings and problems, including a poor study design, were observed in some. Further randomized, double-blind, placebo-controlled studies comprising larger sample sizes, a longer duration of treatment, and longer follow-up assessments are required.

  16. The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy.

    Science.gov (United States)

    Themistocleous, Andreas C; Ramirez, Juan D; Shillo, Pallai R; Lees, Jonathan G; Selvarajah, Dinesh; Orengo, Christine; Tesfaye, Solomon; Rice, Andrew S C; Bennett, David L H

    2016-05-01

    Disabling neuropathic pain (NeuP) is a common sequel of diabetic peripheral neuropathy (DPN). We aimed to characterise the sensory phenotype of patients with and without NeuP, assess screening tools for NeuP, and relate DPN severity to NeuP. The Pain in Neuropathy Study (PiNS) is an observational cross-sectional multicentre study. A total of 191 patients with DPN underwent neurological examination, quantitative sensory testing, nerve conduction studies, and skin biopsy for intraepidermal nerve fibre density assessment. A set of questionnaires assessed the presence of pain, pain intensity, pain distribution, and the psychological and functional impact of pain. Patients were divided according to the presence of DPN, and thereafter according to the presence and severity of NeuP. The DN4 questionnaire demonstrated excellent sensitivity (88%) and specificity (93%) in screening for NeuP. There was a positive correlation between greater neuropathy severity (r = 0.39, P < 0.01), higher HbA1c (r = 0.21, P < 0.01), and the presence (and severity) of NeuP. Diabetic peripheral neuropathy sensory phenotype is characterised by hyposensitivity to applied stimuli that was more marked in the moderate/severe NeuP group than in the mild NeuP or no NeuP groups. Brush-evoked allodynia was present in only those with NeuP (15%); the paradoxical heat sensation did not discriminate between those with (40%) and without (41.3%) NeuP. The "irritable nociceptor" subgroup could only be applied to a minority of patients (6.3%) with NeuP. This study provides a firm basis to rationalise further phenotyping of painful DPN, for instance, stratification of patients with DPN for analgesic drug trials.

  17. Association of glycaemic variability evaluated by continuous glucose monitoring with diabetic peripheral neuropathy in type 2 diabetic patients.

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    Hu, Yu-Ming; Zhao, Li-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Xu, Feng; Chen, Tong; Wang, Xue-Qin; Guo, Ai-Song; Li, Jian-An; Su, Jian-Bin

    2018-02-06

    Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48-6.01), 1.10 (1.03-1.17), 1.24 (1.09-1.41), and 1.33 (1.15-1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%. In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.

  18. 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.

  19. Comparison of electrochemical skin conductance and vibration perception threshold measurement in the detection of early diabetic neuropathy.

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    Amit Goel

    Full Text Available The early diagnosis of diabetic peripheral neuropathy (DPN is challenging. Sudomotor dysfunction is one of the earliest detectable abnormalities in DPN. The present study aimed to determine the diagnostic performance of the electrochemical skin conductance (ESC test in detecting early DPN, compared with the vibration perception threshold (VPT test and diabetic neuropathy symptom (DNS score, using the modified neuropathy disability score (NDS as the reference standard. Five hundred and twenty-three patients with type 2 diabetes underwent an NDS-based clinical assessment for neuropathy. Participants were classified into the DPN and non-DPN groups based on the NDS (≥ 6. Both groups were evaluated further using the DNS, and VPT and ESC testing. A receiver-operator characteristic (ROC curve analysis was performed to compare the efficacy of ESC measurements with those of DNS and VPT testing in detecting DPN. The DPN group (n = 110, 21% had significantly higher HbA1c levels and longer diabetes durations compared with the non-DPN group (n = 413. The sensitivity of feet ESC 15 V, and DNS ≥ 1, were 16.4, 10.9 and 1.8, respectively. ESC measurement is an objective and sensitive technique for the early detection of DPN. Feet ESC measurement was superior to VPT testing for identifying patients with early DPN.

  20. Alpha Lipoic Acid for Symptomatic Peripheral Neuropathy in Patients with Diabetes : A Meta-Analysis of Randomized Controlled Trials

    NARCIS (Netherlands)

    Mijnhout, Gerritje S.; Kollen, Boudewijn J.; Alkhalaf, Alaa; Kleefstra, Nanno; Bilo, Henk J. G.

    2012-01-01

    Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. The databases MEDLINE and EMBASE were searched using the key words "lipoic acid",

  1. 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…

  2. Comparison of electrochemical skin conductance and vibration perception threshold measurement in the detection of early diabetic neuropathy.

    Science.gov (United States)

    Goel, Amit; Shivaprasad, Channabasappa; Kolly, Anish; Sarathi H A, Vijaya; Atluri, Sridevi

    2017-01-01

    The early diagnosis of diabetic peripheral neuropathy (DPN) is challenging. Sudomotor dysfunction is one of the earliest detectable abnormalities in DPN. The present study aimed to determine the diagnostic performance of the electrochemical skin conductance (ESC) test in detecting early DPN, compared with the vibration perception threshold (VPT) test and diabetic neuropathy symptom (DNS) score, using the modified neuropathy disability score (NDS) as the reference standard. Five hundred and twenty-three patients with type 2 diabetes underwent an NDS-based clinical assessment for neuropathy. Participants were classified into the DPN and non-DPN groups based on the NDS (≥ 6). Both groups were evaluated further using the DNS, and VPT and ESC testing. A receiver-operator characteristic (ROC) curve analysis was performed to compare the efficacy of ESC measurements with those of DNS and VPT testing in detecting DPN. The DPN group (n = 110, 21%) had significantly higher HbA1c levels and longer diabetes durations compared with the non-DPN group (n = 413). The sensitivity of feet ESC 15 V, and DNS ≥ 1, were 16.4, 10.9 and 1.8, respectively. ESC measurement is an objective and sensitive technique for the early detection of DPN. Feet ESC measurement was superior to VPT testing for identifying patients with early DPN.

  3. 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.

  4. 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.

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

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    Tianyi He

    2017-01-01

    Full Text Available 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<0.001. The ROC curve analysis showed the areas under the ROC curve were both 0.75 for ESCs of hands and feet in screening DCAN. And the optimal cut-off values of ESCs, sensitivities, and specificities were 76 μS, 76.7%, and 75.6% for hands and 75 μS, 80.0%, and 60.0% for feet, respectively. Conclusions. ESC measurement is a reliable and feasible method to screen DCAN in the Chinese population with diabetes before further diagnosis with CARTs.

  6. Rare Nav1.7 variants associated with painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Blesneac, Iulia; Themistocleous, Andreas C; Fratter, Carl; Conrad, Linus J; Ramirez, Juan D; Cox, James J; Tesfaye, Solomon; Shillo, Pallai R; Rice, Andrew S C; Tucker, Stephen J; Bennett, David L H

    2017-11-22

    Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of DPN patients develop neuropathic pain for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis, for better patient stratification in clinical trials and to target therapy more appropriately. Here we examined the relationship between variants in the voltage gated sodium channel Nav1.7 and neuropathic pain in a deeply phenotyped cohort of patients with DPN. While no rare variants were found in 78 participants with painless DPN, we identified twelve rare Nav1.7 variants in ten (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other neuropathic pain disorders and seven have not previously been linked to neuropathic pain. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of two of the novel variants (M1852T and T1596I) demonstrated gain of function changes as a consequence of markedly impaired channel fast inactivation. By using a structural model of Nav1.7 we were also able provide further insight into the structural mechanisms underlying fast activation and the role of the C-terminal domain in this process. Our observations suggest that rare Nav1.7 variants contribute to the development neuropathic pain in patients with diabetic peripheral neuropathy. Their identification should aid understanding of sensory phenotype, patient stratification and help target treatments effectively.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  7. 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.

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

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    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...... duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices. RESULTS: Serum levels of vitamin B12 were significantly...... lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (pvitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0...

  9. Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

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    Eun-Hee Jang

    2012-08-01

    Full Text Available BackgroundThe aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN in patients with type 2 diabetes mellitus.MethodsTwo hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test.ResultsThe mean age, body mass index (BMI, and duration of diabetes of the study population were 60±14 years (mean±standard deviation, 25.1±4.2 kg/m2, and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R2=4.9%, P=0.013 in an unadjusted model, but only in women. This statistical association was preserved after adjusting for age and BMI (R2=9.8%, P=0.0072.ConclusionThe results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.

  10. 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.

  11. 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).

  12. Effects of isoflurane and sevoflurane anesthesia on arteriovenous shunt flow in the lower limb of diabetic patients without autonomic neuropathy.

    Science.gov (United States)

    Negoro, Takaaki; Mizumoto, Kazuhiro; Ogawa, Koji; Hironaka, Yasuo; Kakutani, Tetsuya; Hatano, Yoshio

    2007-07-01

    Failure of sympathetic nerve control caused by diabetic neuropathy results in vasodilation of arteriovenous shunts. The aim of this study was to test the hypothesis that the function of arteriovenous anastomoses was disordered in mild diabetic patients without apparent neuropathy, and that volatile anesthetics opened arteriovenous shunts more greatly in nondiabetic patients than diabetic patients. Autonomic system function was assessed by cardiovascular reflex tests. Arterial-venous oxygen content difference (A-VDeltaO2) and partial oxygen pressure index (Pvo2/Pao2, the ratio of oxygen tension in femoral vein blood to that in femoral artery blood) were measured before and during isoflurane or sevoflurane anesthesia in 16 diabetic and 22 nondiabetic patients. Skin temperatures of the foot and leg were measured in 14 diabetic and 15 nondiabetic patients using thermography before and during anesthesia. Pvo2/Pao2 before anesthesia was significantly higher in diabetic patients. In nondiabetics, venous oxygen content significantly increased and A-VDeltaO2 markedly decreased during anesthesia, but these parameters were unchanged in diabetics. Foot temperatures were higher in diabetics before anesthesia, and increased gradually and significantly in both groups during anesthesia, but with a greater increase in nondiabetic patients. Induction of anesthesia caused a larger decrease in leg temperature in diabetics than in nondiabetics. Diabetic patients have a higher Pvo2/Pao2 and a small core-to-peripheral temperature gradient before anesthesia, suggesting latent dysfunction of the autonomic nerve system, even in the absence of autonomic neuropathy. Volatile anesthesia opens the arteriovenous shunt in nondiabetics to a greater extent than in diabetic patients.

  13. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy.

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    Watson, C Peter N; Moulin, Dwight; Watt-Watson, Judith; Gordon, Allan; Eisenhoffer, John

    2003-09-01

    Painful neuropathy is one of the most common long-term complications of diabetes mellitus and often proves difficult to relieve. Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health-related quality of life (QOL) while receiving controlled-release (CR) oxycodone (OxyContin) or active placebo. Patients underwent washout from all opioids 2-7 days before randomization to 10 mg CR oxycodone or active placebo (0.25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325-650 mg q4-6h prn was provided as rescue. Thirty-six patients were evaluable for efficacy (21 men, 15 women, mean age 63.0+/-9.4 years). CR oxycodone resulted in significantly lower (P=0.0001) mean daily pain (21.8+/-20.7 vs. 48.6+/-26.6 mm VAS), steady pain (23.5+/-23.0 vs. 47.6+/-30.7 mm VAS), brief pain (21.8+/-23.5 vs. 46.7+/-30.8 mm VAS), skin pain (14.3+/-20.4 vs. 43.2+/-31.3 mm VAS), and total pain and disability (16.8+/-15.6 vs. 25.2+/-16.7; P=0.004). Scores from 6 of the 8 SF-36 domains and both summary scales, Standardized Physical Component (P=0.0002) and Standardized Mental Component (P=0.0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P=0.0001). CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.

  14. Serum B12 Levels in Type II Diabetics on Metformin Therapy and its association with Clinical Neuropathy

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    MP, Holay; M, Vyawahare; K, Shekar

    2017-01-01

    Background: Metformin use in type II DM has also been known to cause B12 deficiency in as reported many studies. Iatrogenic neuropathy caused by Metformin induced B12 deficiency can add to burden of peripheral neuropathy that already exists in diabetic patients. Aims and Objectives: 1)To determine the serum vitamin B12 levels in patients of type II DM on metformin therapy and compare it with those not on metformin therapy; 2) To correlate serum vitamin B12 levels with dose and duration of met...

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

    Science.gov (United States)

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

    2013-11-27

    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 Guideline for the Pharmacologic Management of Neuropathic pain. Because selective serotonin re-uptake inhibitors show limited analgesic effects in PDN, we examined whether the potent analgesic effect of DLX contributes toward improving the pathologically aberrant noradrenaline homeostasis in diabetic models. In streptozotocin (STZ) (50 mg/kg, i.v.)-induced diabetic rats that exhibited robust mechanical allodynia and thermal hyperalgesia, DLX (10 mg/kg, i.p.) significantly and markedly increased the nociceptive threshold. The analgesic effect of DLX was nullified by the prior administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) (50 mg/kg, i.p.), which drastically eliminated dopamine-beta-hydroxylase- and norepinephrine transporter-immunopositive fibers in the lumbar spinal dorsal horn and significantly reduced the noradrenaline content in the lumbar spinal cord. The treatment with DSP-4 alone markedly lowered the nociceptive threshold in vehicle-treated non-diabetic rats; however, this pro-nociceptive effect was occluded in STZ-treated diabetic rats. Furthermore, STZ-treated rats exhibited a higher amount of dopamine-beta-hydroxylase- and norepinephrine transporter-immunopositive fibers in the dorsal horn and noradrenaline content in the spinal cord compared to vehicle-treated rats. Impaired noradrenaline-mediated regulation of the spinal nociceptive network might underlie exaggerated nociception in PDN. DLX might exert its analgesic effect by selective enhancement of

  16. 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.

  17. Plantar thermography is useful in the early diagnosis of diabetic neuropathy

    Science.gov (United States)

    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

  18. Morphological changes of the peripheral nerves evaluated by high-resolution ultrasonography are associated with the severity of diabetic neuropathy, but not corneal nerve fiber pathology in patients with type 2 diabetes.

    Science.gov (United States)

    Ishibashi, Fukashi; Taniguchi, Miki; Kojima, Rie; Kawasaki, Asami; Kosaka, Aiko; Uetake, Harumi

    2015-05-01

    To evaluate the morphological changes of the median and posterior tibial nerve using high-resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients. The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high-resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy. The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P neuropathy (P neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor. The morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology.

  19. 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.

  20. Reactive Eccrine Syringofibroadenoma Associated with Neuropathy, Venous Stasis, and Diabetic Foot Ulcer.

    Science.gov (United States)

    Sirikham, Thirawut; Rojhirunsakool, Salinee; Vachiramon, Vasanop

    2016-01-01

    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.

  1. Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy.

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    Keiko Naruse

    Full Text Available Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV, sensory nerve conduction velocity (SNCV, sciatic nerve blood flow (SNBF, mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.

  2. 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.

  3. Opioid use in the management of diabetic peripheral neuropathy (DPN) in a large commercially insured population.

    Science.gov (United States)

    Patil, Pravinkumar R; Wolfe, Jonathan; Said, Qayyim; Thomas, Jeremy; Martin, Bradley C

    2015-05-01

    To examine the proportion of diabetic peripheral neuropathy (DPN) patients receiving pharmacologic DPN treatments and specifically to identify the rates and factors associated with opioid use and first-line opioid use. A 10% sample of IMS-LifeLink claims data from 1998 through 2008 was used. The study population consisted of diabetic patients who met DPN criteria using a validated DPN algorithm. Multivariable logistic regression controlling for demographics, comorbidities, and other clinical characteristics was used to identify factors associated with any DPN pharmacologic treatment, any opioid use, and first-line opioid treatment. Sensitivity analyses were conducted to explore variations in exclusion criteria as well as opioid use definitions. A total of 666 DPN patients met inclusion criteria and pharmacologic treatment was received by 288 patients (43.24%) and of those, 154 (53.47%) had DPN-related opioid use and 96 (33.33%) received opioid as first-line treatment. Persons with diabetic complications were more likely to use opioids (odds ratio=4.53; 95% confidence interval, 1.09-18.92). Food and Drug Administration-approved DPN agents duloxetine 1.04% (n=3) and pregabalin 5.56% (n=16) had much lower rates of use. DPN-related drug use and DPN-related opioid usage increased as we used less restrictive samples in sensitivity analyses. Opioids were the most frequently prescribed first-line agents for DPN. More than 50% of DPN patients remained untreated with pharmacologic agents 1 year after a DPN diagnosis.

  4. Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus at High Risk for Foot Ulcers.

    Science.gov (United States)

    Menon, Anil S; Dixit, Abhinav; Garg, M K; Girish, R

    2017-01-01

    To study the prevalence of cardiac autonomic neuropathy (CAN) in patients with Type 2 diabetes mellitus at high risk for foot ulcers. We screened patients attending diabetic clinic for identifying patients at high risk for foot ulcers. Those with foot risk category 1, 2 and 3 as per criteria of Foot Care Interest Group were subjected to battery of cardiovascular autonomic reflex tests. Those with one abnormal test were termed as probable CAN and those with two abnormal tests as definite CAN. Those with postural fall in blood pressure with one other abnormal test were termed to have advanced CAN. A total of 74 patients were recruited in the study. The prevalence of abnormal cardiovascular autonomic reflex test was sustained hand grip 81%, E/I ratio 66.2%, 30:15 ratio 28.3% and orthostatic hypotension 13.5%. The prevalence of possible CAN was 31.0% (23/74) and definite CAN was 66.2% (49/74). Ten patients had advanced CAN. There was no observable difference in presence of probable or definite CAN in three risk category for foot ulcers. We found a high prevalence of CAN in subgroup of diabetic patients at increased risk for foot ulcer.

  5. Forefoot ulcer risk is associated with foot type in patients with diabetes and neuropathy.

    Science.gov (United States)

    Molines-Barroso, R J; Lázaro-Martínez, J L; Aragón-Sánchez, F J; Álvaro-Afonso, F J; García-Morales, E; García-Álvarez, Y

    2016-04-01

    To stratify the ulceration risk according to the foot morphology in people with diabetes and a history of forefoot neuropathic ulceration. A cross-sectional study was performed on 139 neuropathic individuals with diabetes and previous forefoot ulcers between January 2012 and February 2014. Foot position of the participants was evaluated by using the foot-posture index. A multivariate analysis adjusted for confounding variables was performed with the ulceration risk factors that were found in the univariate analysis. Two hundred and fifty-eight feet were analysed, 104 (40.3%) feet had a history of ulceration on the forefoot and 154 (59.7%) feet had no previous ulceration. Two positive tests of neuropathy (pfoot type (p=0.039) showed an association with ulceration risk in multivariate analyses. Pronated feet showed a higher risk of ulceration than supinated feet (p=0.011; CI[1.253-5.708] OR 2.675), while significant differences between neutral and supinated feet were not found (p=0.221; CI[0.719-2.753] OR 1.476). A pronated foot has a higher risk of ulceration on the forefoot in neuropathic people with deformities and diabetes mellitus. Foot type should be evaluated in people at risk of ulceration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature.

    Science.gov (United States)

    Alleman, Cathelijne J M; Westerhout, Kirsten Y; Hensen, Marja; Chambers, Colette; Stoker, Malcolm; Long, Stephen; van Nooten, Floortje E

    2015-08-01

    Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. A systematic literature review was conducted to provide an overview of published literature in the last 10-years on the epidemiology, humanistic burden and economic burden of PDPN in Europe. A search was performed according to pre-defined strategy and review criteria in Embase, Pubmed, and conference proceedings databases from 2003 till December 2012. In total, 30 publications written in English covering the relevant patient population and topics of interest. European prevalence ranges from 6% to 34% in diabetes mellitus patients. PDPN has a significant humanistic and economic impact. Patients are limited in their general functioning and their ability to sleep and often experience anxiety and depression. Not surprisingly, PDPN is associated with reduced Health-Related-Quality-of-Life (HRQoL). PDPN patients incur high health care costs due to hospitalizations and outpatient visits. In addition, the painful symptoms cause impaired work productivity. Studies suggest both humanistic and economic burden increase with higher pain severity. The burden from PDPN appears to be higher with increasing pain severity. More severe pain leads to a higher impairment in daily functioning, sleep and HRQoL. Higher pain intensity also leads to increasing healthcare costs and work productivity losses. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. 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.

  8. Autonomic Neuropathy

    Science.gov (United States)

    ... home. Accessed April 30, 2015. Tesfaye S. Neuropathy in diabetes. Medicine. 2015;43:26. Accessed May 13, 2015. Coon E (expert opinion). Mayo Clinic, Rochester, Minn. May 14, 2015. June 06, 2015 Original article: http://www.mayoclinic.org/diseases-conditions/autonomic- ...

  9. Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

    Science.gov (United States)

    Fernando, Malindu Eranga; Crowther, Robert George; Pappas, Elise; Lazzarini, Peter Anthony; Cunningham, Margaret; Sangla, Kunwarjit Singh; Buttner, Petra; Golledge, Jonathan

    2014-01-01

    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. 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). 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, pdiabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

  10. Microcurrent transcutaneous electric nerve stimulation in painful diabetic neuropathy: a randomized placebo-controlled study.

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    Gossrau, Gudrun; Wähner, Michael; Kuschke, Marion; Konrad, Birgit; Reichmann, Heinz; Wiedemann, Bärbel; Sabatowski, Rainer

    2011-06-01

    Diabetes is a common health care problem in western countries. Painful diabetic neuropathy (PDN) might be one of the consequences of long ongoing diabetes; it is estimated that approximately 20% of European diabetic patients suffer from PDN. Transcutaneous electrical nerve stimulation (TENS) is often used as additional pain treatment. However, recent studies show inconsistent results. We aimed to assess the effect of micro-TENS in reducing neuropathic pain in patients with PDN in a placebo-controlled, single-blinded, and randomized design. DESIGN/SETTING/PATIENTS/OUTCOME MEASURES: 22 diabetic patients have been treated with a micro-TENS therapy and 19 patients have been treated with a placebo therapy. Treatment duration was 4 weeks with three therapeutical settings per week. Standardized questionnaires (Pain Disability Index [PDI], neuropathic pain score [NPS], Center for Epidemiologic Studies Depression Scale [CES-D]) were used to assess pain intensity, pain disability, as well as quality of life at baseline at the end of the treatment period and 4 weeks after treatment termination. Patients with a minimum of 30% reduction in NPS were defined as therapy responders. After 4 weeks of treatment, 6/21 patients in the verum group vs 10/19 patients in the placebo group responded to therapy. The median PDI score after 4 weeks of treatment showed a reduction of 23% in the verum vs 25% in the placebo group. The differences did not reach statistical significance. The pain reduction with the applied transcutaneous electrotherapy regimen is not superior to a placebo treatment. Wiley Periodicals, Inc.

  11. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping of blood pressure during night time

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    Hjortkær, Henrik; Jensen, Tonny; Kofoed, Klaus

    2014-01-01

    INTRODUCTION: Cardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been demon...

  12. 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 (Pfoot massage group showed better improvement in TUG than the control group (pfoot massage 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.

  13. Effects of Thai Foot Massage on Balance Performance in Diabetic Patients with Peripheral Neuropathy: A Randomized Parallel-Controlled Trial

    Science.gov (United States)

    Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro

    2015-01-01

    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/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. PMID:25892354

  14. 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. PMID:26457582

  15. Prevalence of cardiac autonomic neuropathy in Asian Indian patients with fibrocalculous pancreatic diabetes

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    Amrit Nanaiah

    2012-01-01

    Full Text Available Background: It was formerly believed that since fibrocalculous pancreatic diabetes (FCPD is a secondary form of diabetes, specific diabetic complications were uncommon. This is no longer considered to be true. Our objective was to study the prevalence and pattern of cardiac autonomic neuropathy (CAN in patients with FCPD. Materials and Methods: A cross-sectional study on consecutive male patients with FCPD was performed. Using an automated CAN System Analyzer, heart rate response to deep breathing, Valsalva maneuver, standing and blood pressure response to standing were measured. The standard Ewing′s criteria were used to define normal, borderline, and abnormal values. Prevalence rates were calculated and the patients were defined to have normal autonomic function, parasympathetic, sympathetic, and combined dysfunction. Results: The prevalence of CAN in this study population was 63.3%. Isolated parasympathetic dysfunction (42.3% was the most common abnormality. Combined sympathetic and parasympathetic dysfunction was noted in 13.3% of patients. Isolated borderline dysfunction was noted among 13.3% of patients. CAN was detected in six patients with a duration of diabetes of less than 1 year after diagnosis. Patients with autonomic dysfunction were found to have a lower body mass index (BMI and low density lipoprotein (LDL-cholesterol when compared to those with normal autonomic functions, which was not statistically significant. Conclusion: The prevalence of abnormal cardiac autonomic function is as high as 63.3% in the present study population which warrants regular screening of patients with FCPD for autonomic dysfunction. Patients with FCPD and autonomic dysfunction were found to have a lower BMI and lower LDL-cholesterol, which may be indicators of malnutrition in the group with autonomic dysfunction. Whether this malnutrition contributes to autonomic dysfunction needs further exploration.

  16. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.

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    Ahmed, Marwan A; Muntingh, George; Rheeder, Paul

    2016-10-07

    The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations 6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053). Close to third of metformin

  17. Anxiety affects disability and quality of life in patients with painful diabetic neuropathy.

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    Geelen, C C; Smeets, R J E M; Schmitz, S; van den Bergh, J P; Goossens, M E J B; Verbunt, J A

    2017-11-01

    Painful diabetic neuropathy (PDN) is known to negatively affect psychosocial functioning as expressed by enhanced levels of anxiety and depression. The aim of this study was to specify diabetes and pain-related fears. This questionnaire-based cross-sectional study included 154 patients with PDN (mean age 65.7 ± 6.6 years). Correlation analyses corrected for age, gender, pain intensity, pain duration and insulin treatment were performed to assess the associations of fear of hypoglycaemia (Hypoglycaemia Fear Survey, HFS), kinesiophobia (Tampa Scale of Kinesiophobia, TSK), fear of pain (Pain Anxiety Symptom Scale, PASS-20), fear of falling (Falls Efficacy Scale-I, FES-I), fear of fatigue (Tampa Scale of Fatigue, TSF) and fear of negative evaluation (Brief Fear of Negative Evaluation Scale, BFNE), with quality of life (QoL) (Norfolk Quality of Life Questionnaire, Diabetic Neuropathy Version, QOL-DN) and disability (Pain Disability Index, PDI), respectively. In univariate analyses, all fears were independently associated with QOL-DN and PDI (p < 0.001 for all variables). Linear regression models including all fears and confounders, showed that pain intensity, pain duration and FES-I were significantly associated with QOL-DN (R(2)  = 0.603). Pain intensity, male gender and FES-I were significantly associated with PDI (R(2)  = 0.526). After controlling for confounders, levels of pain intensity, duration of pain and fear of falling were negatively associated with QoL in patients with PDN. Pain intensity, male gender and fear of falling were positively associated with disability. Specifying fears enables us to identify potential targets for behavioural interventions that aim to improve psychosocial well-being in patients with PDN. This study shows that patients with PDN suffer from various fears, which should enable us to design a treatment strategy that directly targets these fears, hereby improving physical and psychosocial well-being in these patients. © 2017

  18. 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.

  19. System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. [Vibration perception threshold in diagnosing diabetic peripheral neuropathy by receiver operating characteristic curve].

    Science.gov (United States)

    Hou, Yu; Liu, Sha; Zhu, Tingting; Zhang, Huan; Liu, Gang; Zhu, Yan; Chen, Huiling

    2012-09-01

    To evaluate the diagnostic value of vibration perception threshold (VPT) in diabetic peripheral neuropathy (DPN) by the receiver operating characteristic curve (ROC) and to establish its cut-off threshold. All patients had the VPT examination and nerve conduction velocity (NCV) examination. NCV examination showed that 283 patients with Type 2 diabetes were divided into a DPN group (n=151) and an NDPN group (n=132). The VPT diagnosis was evaluated by Youden index, sensitivity, specificity and the area under ROC curve. The best cut-off threshold was defined by the Youden index. 1) The NCV was significantly slower, while the VPT was higher in the DPN group than those in the NDPN group (both P values <0.05). 2) The VPT and NCV of both sides of the limb had no difference in all patients. 3) With NCV as the golden diagnosis criterion, the area under ROC of VPT was 0.707, the best cut-off threshold was 10.54 V, the sensitivity was 0.596, the specificity was 0.848, and the Youden index was 0.445. 4) The diagnosis ratio of NCV combined with VPT was 60.4%, significantly higher than that of NCV alone (P<0.05). Compared with NCV examination, VPT has good diagnostic value for DPN. The best cut-off value is 10.54 V.

  3. 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.

  4. Prevalence and risk factors for peripheral neuropathy among type 2 diabetes mellitus patients at a tertiary care hospital in coastal Karnataka

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    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.

  5. The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy

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    Majid Ghasemi

    2014-01-01

    Full Text Available Background: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN, challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A injections on pain symptoms of patients with diabetic neuropathic pain. Materials and Methods: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20 and placebo groups (normal saline injection, N = 20. The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS and visual analog scale (VAS score and compared in two studied groups. Results: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05. It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05. According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01. Conclusion: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.

  6. A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

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    Giovanna Franconi

    2013-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment.

  7. 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.

  8. Spinal CCL1/CCR8 signaling interplay as a potential therapeutic target - Evidence from a mouse diabetic neuropathy model.

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    Zychowska, Magdalena; Rojewska, Ewelina; Piotrowska, Anna; Kreiner, Grzegorz; Nalepa, Irena; Mika, Joanna

    2017-11-01

    Chemokine signaling has been implicated in the pathogenesis of diabetic neuropathy; however, the involvement of the chemokine CC motif ligand 1 (CCL1)-chemokine CC motif receptor 8 (CCR8) interaction remains unknown. The goal of this study was to examine the role of CCL1-CCR8 signaling interplay in the development of hypersensitivity and in opioid effectiveness in diabetic neuropathy. Primary glial cell cultures and a streptozotocin (STZ; 200mg/kg, intraperitoneal)-induced mouse model of diabetic neuropathy were used. Analysis of mRNA/protein expression of glial markers and CCL1/CCR8 was performed by qRT-PCR, Western blotting and/or protein arrays. The co-localization of CCL1/CCR8 with neural/glial cells was visualized by immunofluorescence. The pharmacological tools were injected intrathecally, and pain behavior was evaluated by von Frey/cold plate tests. Single STZ injection increased blood glucose levels and induced the development of hypersensitivity as measured on days 7-21. On day 7 after STZ, the protein levels of CCL1 and IBA1 but not of CCR8 or GFAP were elevated. Immunofluorescent staining revealed that CCR8 was predominantly localized in neurons, which are also the main source of spinal CCL1. Lipopolysaccharide stimulation of primary microglial cultures resulted in decreases in the levels of CCL1 and CCR8. Single intrathecal injection of CCL1 (10-500ng) induced the development of hypersensitivity, whereas on day 7 after STZ, a CCL1-neutralizing antibody dose-dependently (2-8μg) delayed pain behavior. Repeated administration of the CCL1-neutralizing antibody (4μg) also enhanced the effectiveness of morphine and buprenorphine (1μg). These results reveal that CCL1/CCR8 neuronal signaling plays an important role in the development of diabetic neuropathy and the effectiveness of opioids. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

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    Ahmed, Marwan A.; Muntingh, George; Rheeder, Paul

    2016-01-01

    Background The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients ...

  10. Effects of Xueshuantong combined with antioxidant drugs on nerve conduction function and oxidative stress in patients with diabetic peripheral neuropathy

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    Yuan-Zhen Chu

    2017-07-01

    Full Text Available Objective: To study the effect of Xueshuantong combined with antioxidant drugs on nerve conduction function and oxidative stress in patients with diabetic peripheral neuropathy. Methods: 138 cases of patients with diabetic peripheral neuropathy who were treated in endocrinology department of our hospital between June 2014 and October 2016 were enrolled and randomly divided into two groups. The combination group received Xueshuantong combined with antioxidant drug therapy, and the control group received antioxidant drug therapy. Before and after treatment, the nerve conduction velocity as well as serum content of oxidative stress indexes and nerve cytokines was measured. Results: 4 weeks and 8 weeks after treatment, common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of both groups were significantly higher than those before treatment while serum MDA, AOPP and 8-OHdG levels were significantly lower than those before treatment, and common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of combination group were significantly higher than those of control group while serum MDA, AOPP and 8-OHdG levels were significantly lower than those of control group. Conclusion: Xueshuantong combined with antioxidant drugs can improve the nerve conduction function, inhibit oxidative stress response and improve neurotrophy status in patients with diabetic peripheral neuropathy.

  11. 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. Copyright © 2014 Mosby, Inc. All rights reserved.

  12. Association of patient-rated severity with other outcomes in patients with painful diabetic peripheral neuropathy

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    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

  13. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials

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    Derry Sheena

    2008-08-01

    Full Text Available Abstract Background Duloxetine hydrochloride is a reuptake inhibitor of 5-hydroxytryptamine and norepinephrine used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in painful diabetic neuropathy and fibromyalgia to allow comparison with other antidepressants. Methods We searched PubMed, EMBASE (via Ovid, and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain. Results We identified six trials with 1,696 patients: 1,510 were treated with duloxetine and 706 with placebo. All patients had established baseline pain of at least moderate severity. Trial duration was 12 to 13 weeks. Three trials enrolled patients with painful diabetic neuropathy (PDN and three enrolled patients with fibromyalgia. The number needed to treat (NNT for at least 50% pain relief at 12 to 13 weeks with duloxetine 60 mg versus placebo (1,211 patients in the total comparison was 5.8 (95% CI 4.5 to 8.4, and for duloxetine 120 mg (1,410 patients was 5.7 (4.5 to 5.7. There was no difference in NNTs between PDN and fibromyalgia. With all doses of duloxetine combined (20/60/120 mg there were fewer withdrawals for lack of efficacy than with placebo (number needed to treat to prevent one withdrawal 20 (13 to 42, but more withdrawals due to adverse events (number needed to harm (NNH 15 (11 to 25. Nausea, somnolence, constipation, and reduced appetite were all more common with duloxetine than placebo (NNH values 6.3, 11, 11, and 18 respectively. The results for duloxetine are compared with published data for other antidepressants in neuropathic pain. Conclusion Duloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 weeks, and is well tolerated. The NNT of 6 for 50% pain relief suggests that this is likely to be a useful drug in these difficult

  14. Diabetes and nerve damage

    Science.gov (United States)

    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 ...

  15. The effects of isometric exercises and stretching on postural stability in Non–Insulin Dependent Diabetes Mellitus patients with diffuse symmetrical sensory motor neuropathy

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    S. Nenkova

    2009-02-01

    Full Text Available The purpose of this study was to explore the effects of isometric exercises and stretching on postural stability in Non – Insulin Dependent Diabetes Mellitus (NIDDM patients with diffuse symmetrical sensory motor neuropathy. Patients were assigned to an experimental group and amatched control group. The experimental group received isometric exer-cises and stretching three times weekly for 12 weeks in addition to routine medication and dietary advice. A t the end of this period, this group wascompared with the control group, which received routine medication anddietary advice only. Measurements of muscle strength of quadriceps, ham-strings, ankle plantar and dorsiflexors, and Romberg’s test for postural sta-bility were carried out before and after the 12 weeks intervention. The study showed that isometric exercises and stretching for the lower extremities improved postural stability (p = 0.00and strength of the quadriceps (p = 0.001 hamstrings (p = 0.001 dorsiflexors (p = 0.001 plantarflexors (p = 0.001in NIDDM patients with diffuse symmetrical sensory motor neuropathy. This exercise regimen also had a loweringeffect on blood glucose level (p = 0.00.  In conclusion it seems that the simple exercise intervention described in thisstudy may be of benefit to these patients if incorporated into their management programmes.

  16. The Effect of Diabetic Peripheral Neuropathy on Ground Reaction Forces during Straight Walking in Stroke Survivors

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    Amirah Mustapa

    2017-01-01

    Full Text Available Purpose. The aim of this present study was to investigate the ground reaction forces (GRFs alterations in stroke survivors with diabetic peripheral neuropathy (DPN. Methods. Ten stroke survivors with DPN, 10 stroke survivors without DPN, and 10 healthy controls with matched body weight between groups participated in this case-control cross-sectional study. Three-dimensional GRFs (anterior-posterior, medial-lateral, and vertical were collected at a comfortable walking speed using the Nexus Vicon motion analysis system and force plate. The Kruskal–Wallis test was used to analyze GRFs parameters. Results. We found significant alterations of medial-lateral forces of the nonparetic side and vertical forces of the paretic side in stroke survivors with DPN compared to stroke survivors without DPN and healthy controls. In addition, there were smaller braking and lower propulsion peak in anterior-posterior forces, smaller magnitude of medial-lateral forces, and lower first and second peak of vertical forces in stroke survivors with DPN compared to stroke survivors without DPN and healthy controls. Conclusion. The study findings identified that GRFs were affected in stroke survivors with DPN on both the paretic and the nonparetic sides. Further investigations are warranted to explore the impact of DPN on the kinematics and muscle activity related to the gait performance in stroke survivors with DPN.

  17. Advantages of early diagnosis of diabetic neuropathy in the prevention of diabetic foot ulcers.

    Science.gov (United States)

    Sanz-Corbalán, Irene; Lázaro-Martínez, José Luis; García-Morales, Esther; Molines-Barroso, Raúl; Álvaro-Afonso, Francisco; García-Álvarez, Yolanda

    2017-12-26

    to evaluate the utility of the sudomotor function test (SFT) as a clinical tool in the Risk Stratification System of diabetic patients and to demonstrate the earlier detection of the risk of developing diabetic foot ulcers (DFU) compared to the standard clinical tests. prospective follow-up study on 263 patients enrolled consecutively over 3.5 years. Diabetic patients without active DFU were classified according to the International Working Group Risk Stratification System (RSS) and categorized according to the results of the Semmes-Wenstein Monofilament (SWM) and biothesiometer measurements or the SFT. The main outcome evaluated was the development of DFU. median follow-up was 42 [38-44] months. Sixty patients (22.8%) developed DFU after a median of 6.2 [3-17] months. Ten patients that were included in the no-risk group (group 0) based on the SWM and biothesiometer results developed DFU. Thus the sensitivity of this approach was 83.33% and the specificity was 50.47%. Based on the SFT results, all patients that developed DFU were included in the correct risk group. This approach had 100% sensitivity and 31.53% specificity. Regarding the diagnostic accuracy of the two Methods, the respective AUC values were 0.776 (95% CI 0.702-0.849) and 0.816 (95% CI 0.757-0.874). SFT improved RSS in diabetic patients in a specialized diabetic foot unit. SFT categorized patients correctly according to the risk of developing DFU. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy.

    Science.gov (United States)

    Billinger, Sandra A; Sisante, Jason-Flor V; Alqahtani, Abdulfattah S; Pasnoor, Mamatha; Kluding, Patricia M

    2017-01-01

    Aerobic exercise improves vascular endothelial function in people with Type 2 diabetes mellitus (T2DM). There is minimal information available regarding vascular health in people with T2DM and diabetic peripheral neuropathy (DPN). Thus, the primary aim of this secondary analysis was to determine whether a 16-week aerobic exercise intervention could improve vascular health in people with T2DM and DPN. A secondary aim was to explore the relationship between changes in flow-mediated dilation (FMD) and the number of years since diagnosis of DPN. We examined whether a 16-week aerobic exercise intervention would improve vascular health in people with T2DM and DPN. We used Doppler ultrasound to assess brachial artery diameter and peak shear at baseline and post-exercise. Paired t-tests were used to determine whether the outcome measures improved from baseline to post-intervention. Pearson correlation assessed the relationship between DPN (years) and the percent change score (pre- to post-intervention) for FMD. Seventeen individuals were included in the data analysis. After the intervention, peak diameter increased (3.9 (0.5) to 4.0 (0.5) mm; p = 0.07). Time to peak shear occurred at 60.5 (24.6) seconds when compared to baseline at 68.2 (22.7) seconds; p = 0.17. We found that a longer duration (in years) of DPN demonstrated a fair, negative relationship (r = -0.41, p = 0.19) with the percent change in FMD. Aerobic exercise was beneficial for improving measures of vascular health but these were not statistically significant. The magnitude of change may be affected by the duration of DPN.

  19. A prospective study of prevalence and association of peripheral neuropathy in Indian patients with newly diagnosed type 2 diabetes mellitus.

    Science.gov (United States)

    Gill, H K; Yadav, S B; Ramesh, V; Bhatia, E

    2014-01-01

    Diabetic peripheral neuropathy (DPN) predisposes to foot ulceration and gangrene. It has been reported that DPN is lower in Indians relative to Caucasians. Studies among recent onset patients with type 2 diabetes mellitus (T2DM) are very few. We studied the prevalence and risk factors of DPN in patients with newly diagnosed T2DM. We prospectively studied 195 consecutive patients over age 30 with a duration of diabetes ≤6 months. All underwent a clinical and biochemical evaluation and were screened for DPN using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) as well as the vibration perception threshold using a biothesiometer. We compared the prevalence of peripheral neuropathy (PN) in 75 age- and sex-matched healthy controls. The cases had a mean age of 47.6 ± 10.2 years (59% males) and duration of symptoms of 5.9 ± 8.2 months prior to presentation. The overall prevalence of DPN was 29.2% [95% CI 22.8-35.7]. PN among matched control was 10.7% (95% CI 3.5-17.8). The prevalence of DPN showed an increasing trend with age (trend chi-square 11.8, P = 0.001). Abnormal vibration perception threshold was present in 43.3% (95% CI 36.3-50.3) of cases and had a significant correlation with NDS (P = 0.000). Abnormal monofilament testing was present in 6.1% of cases (95% CI 2.7- 9.5). A logistic regression analysis showed that DPN was independently associated with age (P = 0.002) and duration of diabetes prior to presentation (P = 0.02) but not with body mass index, plasma glucose, or HbA1c. Our study showed high prevalence of PN in recently diagnosed patients with T2DM, which was independently associated with age and duration of symptoms of diabetes prior to the diagnosis. Screening for DPN at diagnosis of diabetes is warranted, especially among older subjects.

  20. Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis.

    Science.gov (United States)

    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.

  1. 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.

  2. EFFECT OF PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION (PNF IN IMPROVING SENSORIMOTOR FUNCTION IN PATIENTS WITH DIABETIC NEUROPATHY AFFECTING LOWER LIMBS

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    Kamaljeet Singh

    2016-06-01

    Full Text Available Background: Diabetic Mellitus is a group of metabolic disease characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. Distal Sensorimotor Polyneuropathy is the most common complication of diabetes which mainly affects the lower limbs. Most of the studies aimed at individually increasing muscle strength or sensation but not on overall performance enhancements of the diabetic lower limbs. The evidence supporting the effectiveness of PNF in diabetic neuropathic patients is scarce. Methods: 30 patients, with age between 50 to 70 years, diagnosed with Diabetic Sensorimotor Polyneuropathy (DSP were selected from the department of Medicine and department of Neurosurgery Guru Gobind Singh Medical College and Hospital. Patients were evaluated at the beginning and at the end of the intervention using Diabetic Neuropathy Examination scores. Patients received 3 sets of exercises one hour/day with 3 days/week for 3 months. Each set of exercises consists of 5 repetitions of PNF patterns (alternate day and techniques. Results: D1 & D2 patterns of PNF are effective in improving both motor and sensory functions of diabetic patients with neuropathic symptoms. Improvement in muscle strength, reflex and sensations occurred to a greater extent after the treatment of three months in these subjects. This study shows that PNF patterns were effective at enhancing sensorimotor problems of lower limbs. Conclusion: This study concluded that PNF is found to be effective in improving sensorimotor functions of diabetic neuropathic patients affecting lower limbs.

  3. 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

  4. 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.

  5. 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. Painful diabetic peripheral neuropathy is a common complication of diabetes mellitus and the

  6. 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...

  7. 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.

  8. A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice

    Science.gov (United States)

    Bhanot, Abhishek; Shri, Richa

    2010-01-01

    Introduction: Diabetic Neuropathy (DN) is a major microvascular complication of uncontrolled diabetes. This may result from increased oxidative stress that accompanies diabetes. Hence plants with antioxidant action play an important role in management of diabetes and its complications. Materials and Methods: This study was designed to evaluate preventive as well as curative effect of methanol extracts of outer scales and edible portions of two plants with established antioxidant action - Allium cepa and Allium sativum, in induced DN in albino mice. Mice were divided into control, diabetic and test extracts treated groups. Test extracts were administered daily at a dose of 200 mg/kg p.o. for 21 days, in the preventive group prior to onset of DN, and in the curative group after the onset of DN. Hyperalgesia and oxidative stress markers were assessed. STZ-diabetic mice showed a significant thermal hyperalgesia (as assessed by the tail-flick test), indicating development of DN. Results: Treatment with test extracts prevented loss in body weight, decreased plasma glucose level, and significantly ameliorated the hyperalgesia, TBARS, serum nitrite and GSH levels in diabetic mice. Conclusion: Methanol extract of outer scales of onion has shown most significant improvement; may be due to higher content of phenolic compounds in outer scales of A. cepa. PMID:21713142

  9. Diabetic peripheral neuropathy therapy-induced activation of humoral serotonin and endogenous neurotrophins

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    Yuulia Vladimirovna Karakulova

    2013-01-01

    Full Text Available The indicators of pain and psychological status, the concentrations of serum serotonin and blood platelets, and the levels of brain-derived neurotrophic factor (BDNF and nerve growth factor were studied in 82 patients with diabetic peripheral neuropathy (DPN. Along with conventional treatment aimed to normalize carbohydrate metabolism, 30 patients with DPN received actovegin in an intravenous, jetwise dose of 10.0 ml for 10 days. Prior to treatment, their pain intensity was 5.94±1.2 and 29.6±6.24 scores according to a visual analogue scale (VAS and PainDETECT, respectively. The subclinical level of anxiety and depression was noted. The amount of serotonin in the serum (90.39±55.43 ng/ml and blood platelets (298.13±80.33 ng/ml was lower than that in the control. The content of serum BDNF in DPN was also substantially lower (419.27±132.7 pg/ml; p<0.04 than that in the control. After treatment, the actovegin group showed a more significant reduction in pain syndrome according to the VAS (3.5±0.6 cm; p=0.005 and PainDETECT (19.4±4.1 scores, p=0.005, a decrease in the degree of anxiety and depression according to the Beck inventory (11.4±1.4 scores; p=0.001, and an increase in BDNF levels up to 979.71±289.9 pg/ml. Serum serotonin and blood platelets increased up to 206.13±78.3 and 477.06±114.45 ng/ml, respectively; which is indicative of the correct choice of the treatment for DPN.

  10. 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%; ppeople with DMPN, the greater proportion of negative work may negatively affect foot structures during forward propulsion, when positive work and foot stability should predominate. Further study is recommended to determine how both MF and RF kinetics influence the development of deformity and ulceration in people with DMPN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Population pharmacokinetics of pregabalin in healthy subjects and patients with post-herpetic neuralgia or diabetic peripheral neuropathy

    Science.gov (United States)

    Shoji, Satoshi; Suzuki, Misaki; Tomono, Yoshiro; Bockbrader, Howard N; Matsui, Shigeyuki

    2011-01-01

    AIM Pregabalin, a chemical analogue of the mammalian neurotransmitter γ-aminobutyric acid, has been approved in many countries for partial-onset seizures, generalized anxiety disorder and various other pain disorders, including neuropathic pain associated with post-herpetic neuralgia and diabetic peripheral neuropathy and fibromyalgia. The aim of this study was to develop a population pharmacokinetic model and quantify the influence of covariates on the parameters. METHODS This pregabalin population pharmacokinetic analysis was conducted on data from 14 clinical trials involving healthy subjects, subjects with impaired renal function and patients with post-herpetic neuralgia or diabetic peripheral neuropathy (n = 616). The data analysis was performed using nonlinear mixed effects modelling methodology as implemented by NONMEM. RESULTS A one-compartment model with first-order absorption and elimination adequately described pregabalin pharmacokinetics. The model indicated that pregabalin apparent clearance (CL/F) was proportional to estimated creatinine clearance (CLcr). The pregabalin systemic exposure in patients with lower renal function who received pregabalin 150 mg twice daily was almost equal to that of patients with normal renal function administered pregabalin 300 mg twice daily. The systemic exposure stratified by lower or normal renal function was similar between patients with post-herpetic neuralgia and diabetic peripheral neuropathy. CONCLUSION The developed model identified CLcr and ideal body weight as clinically influential covariates on CL/F and volume of distribution, respectively. This study indicates that renal function accounts for variability in the apparent clearance of pregabalin which is consistent with what is known about the elimination of this drug. PMID:21306415

  12. A Comparison of Screening Tools for the Early Detection of Peripheral Neuropathy in Adults with and without Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jennifer J. Brown

    2017-01-01

    Full Text Available Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN in overweight, obese, and inactive (OOI adults or those who have prediabetes (PD or type 2 diabetes (T2D. Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1 were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D. Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP and sural nerve conduction velocity (SNCV. All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.

  13. Assessment of muscle mass, risk of falls and fear of falling in elderly people with diabetic neuropathy

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    Hudson Azevedo Pinheiro

    Full Text Available Abstract Objective : To assess muscle mass, risk of falls and fear of falling in elderly adults with diabetic neuropathy (DNP. Methods : 50 elderly patients with diabetes mellitus (DM and diabetic neuropathy (NPD participated in this study. Risk of falling was assessed using the Berg Balance Scale (BBS. Fear of falling was assessed by means of the Falls Efficacy Scale-International (FES-I. Muscle mass was assessed by tetrapolar bioimpedance analysis (BIA and Janssen's equation. Subjects were divided into two groups: one with a history of falls in the six months before study enrollment (G1 and the other without history of falls (G2. Results : There were statistically significant differences between G1 and G2 regarding lean body mass (p < 0.05, risk of falls as measured by the BBS (p < 0.01, and fear of falling as measured by the FES-I (p < 0.01. In addition, there was a significant correlation between the BBS and BIA (r = 0.45 and p < 0.01, showing that the greater the lean body mass, the lower the risk of falling. Conclusions : We found an association between lean mass, risk of falls and fear of falling in elderly adults with DNP and a history of falls from own height.

  14. Comparison the effects of two types of therapeutic exercises Frenkele vs. Swiss ball on the clinical balance measures in patients with type II diabetic neuropathy.

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    Rojhani-Shirazi, Zahra; Barzintaj, Fatemeh; Salimifard, Mohamad Reza

    2017-11-01

    The number of diabetic patients is increasing in the world. Peripheral neuropathy is the most important problem of diabetes. Neuropathy eventually leads to balance impairment which is the main cause of falling down in these patients However, not sufficient evidences available to compare different protocols for improving balance in diabetic patients. This study aimed to compare the effects of two therapeutic exercises on clinical balance measures in patients with type II diabetic peripheral neuropathy. The study was performed on 60 patients with diabetes categorized randomly into three groups: an intervention group (N=20) that received ball training exercise, another intervention group (N=20) that received Frenkel exercise and a control group (N=20) that received no interventions. Exercise training session was performed for 3 weeks. Then, clinical balance measures were computed in the three groups. Paired t-test and one-way ANOVA were used to analyze the collected data. Both types of therapeutic exercise programs significantly improved balance in single leg stance, star excursion test, and Berg balance scale test (P˂0.05) compared to the control group. Besides, this was more significant in the ball training group (P˂0.05). To improve balance in diabetic neuropathy, Swiss ball exercise is preferred compared to Frenkel training. Copyright © 2016. Published by Elsevier Ltd.

  15. Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal model of human inflammatory demyelinating neuropathy.

    Science.gov (United States)

    Moalem-Taylor, Gila; Allbutt, Haydn N; Iordanova, Mihaela D; Tracey, David J

    2007-07-01

    Experimental autoimmune neuritis (EAN) is a T cell mediated autoimmune disease of the peripheral nervous system that serves as an animal model of the acute inflammatory demyelinating polyradiculoneuropathy in Guillain-Barre syndrome (GBS). Although pain is a common symptom of GBS occurring in 55-85% of cases, it is often overlooked and the underlying mechanisms are poorly understood. Here we examined whether animals with EAN exhibit signs of neuropathic pain including hyperalgesia and allodynia, and assessed their peripheral nerve autoimmune inflammation. We immunized Lewis rats with peripheral myelin P2 peptide (amino acids 57-81) emulsified with complete Freund's adjuvant, or with adjuvant only as control. P2-immunized rats developed mild to modest monophasic EAN with disease onset at day 8, peak at days 15-17, and full recovery by day 28 following immunization. Rats with EAN showed a significant decrease in withdrawal latency to thermal stimuli and withdrawal threshold to mechanical stimuli, in both hindpaws and forepaws, during the course of the disease. We observed a significant infiltration of T cells bearing alphabeta receptors, and a significant increase in antigen-presenting cells expressing MHC class II as well as macrophages, in EAN-affected rats. Our results demonstrate that animals with active EAN develop significant thermal hyperalgesia and mechanical allodynia, accompanied by pronounced autoimmune inflammation in peripheral nerves. These findings suggest that EAN is a useful model for the pain seen in many GBS patients, and may facilitate study of neuroimmune mechanisms underlying pain in autoimmune neuropathies.

  16. No effect of Pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study

    DEFF Research Database (Denmark)

    Dejgård, A; Hilsted, J

    1988-01-01

    of this therapy we performed a double-blind placebo controlled cross-over study with Pindolol (15 mg/day). Eight Type 1 (insulin-dependent) diabetic patients with autonomic neuropathy and signs and symptoms of orthostatic hypotension (systolic blood pressure decrease greater than 30 mm Hg when standing......Orthostatic hypotension is one of the most troublesome symptoms in diabetic autonomic neuropathy. Some reports have suggested Pindolol - a beta-adrenoceptor antagonist with intrinsic sympathomimetic activity - to be effective in the treatment of this condition. In order to elucidate the value...

  17. Diabetic peripheral neuropathy and its determinants among patients attending a tertiary health care centre in Mangalore, India

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    Monisha D’Souza

    2015-07-01

    Full Text Available Background. The burden of diabetes mellitus (DM is on the rise especially in developing countries like India. Due to its chronic nature DM tends to cause many debilitating complications and diabetic peripheral neuropathy (DPN is one of them. The aim of this study is to determine the prevalence of DPN among patients attending a tertiary care hospital and to identify the determinants associated with it. Design and methods. A cross sectional study was conducted in Government Wenlock Hospital, Mangalore (India, during January-February 2014. A total of 208 patients with >5 year duration of DM were asked to respond to the patient history version of Michigan Neuropathy Screening Instrument (MNSI and examinations were conducted after obtaining consent from them. The statistical analysis was done in terms of descriptive statistics and association between variables was tested using logistic regression test.Results. The prevalence of DPN using the MNSI history version and MNSI examination were found to be 18.3% and 32.2% respectively. The major determinants associated with DPN were found to be male gender (OR: 2.7, CI: 1.4-5.1, P=0.001, smoking (OR: 5.8, CI: 1.9-17.3, P=0.001 and age >40 years (OR: 2.7, CI: 1.2-5.8, P=0.011. Conclusions. The burden of undetected DPN was found to be higher among diabetics, with an especially higher prevalence among males, smokers and those with long standing diabetes mellitus. Interventions in the form of early detection through routine screening, smoking cessation and regular follow up examinations would go a long way in reducing the burden of disability among diabetics and improve their quality of life significantly.

  18. Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: targeting Nrf2/HO-1/NF-kB and COX signalling pathway.

    Science.gov (United States)

    Mittal, Ruchika; Kumar, Anil; Singh, Dhirendra Pratap; Bishnoi, Mahendra; Nag, Tapas Chandra

    2017-11-01

    Emerging role of Nrf-2/HO-1 in pathogenesis of diabetic neuropathy has been suggested. Diabetic neuropathy is one of the most common complications of diabetes and more than 50% patients of diabetes develop diabetic neuropathy. Rutin has been well documented to show protective effect in various complications, e.g., diabetic neuropathy. However, its mechanistic insight is still not completely understood. The present study has been designed to explore the protective effect of rutin and its interaction with COX-2 inhibitor, nimesulide in diabetic neuropathy. DN (diabetic neuropathy) rats were maintained with or without rutin (100 and 200 mg/kg), nimesulide (5 and 10 mg/kg), and their combinations for 8 weeks. Body weight, serum glucose, pain assessment (mechanical allodynia, cold allodynia, mechanical hyperalgesia, and thermal hyperalgesia), and motor nerve conduction velocity (MNCV) were measured in all groups. Oxidative damage was assessed through biochemical estimation and mitochondrial ROS production, followed by inflammatory and apoptotic markers (TNF-α, caspase-3, Nrf-2, HO-1, and NF-kBp65) for their activity, protein, and gene expression. The structural changes were also reported through transmission electron microscope. Streptozotocin injection (55 mg/kg) induced diabetes reduced body weight, reduced the threshold for pain in various pain assessment parameters. Oxidative damage (increased MDA, decreased SOD, catalase, and GSH levels) increased mitochondrial ROS production followed by increased expression of inflammatory markers and decreased expression of Nrf-2/HO-1 in sciatic nerve. Treatment with rutin (100 and 200 mg/kg) and nimesulide (5 and 10 mg/kg) significantly attenuates these alterations as compared to DN control rats. Furthermore, combination of rutin (200 mg/kg) and nimesulide (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone in streptozotocin-treated rats. The present study

  19. Reduced conduction failure of the main axon of polymodal nociceptive C-fibres contributes to painful diabetic neuropathy in rats.

    Science.gov (United States)

    Sun, Wei; Miao, Bei; Wang, Xiu-Chao; Duan, Jian-Hong; Wang, Wen-Ting; Kuang, Fang; Xie, Rou-Gang; Xing, Jun-Ling; Xu, Hui; Song, Xue-Jun; Luo, Ceng; Hu, San-Jue

    2012-02-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus and can affect many aspects of life and severely limit patients' daily functions. Signals of painful diabetic neuropathy are believed to originate in the peripheral nervous system. However, its peripheral mechanism of hyperalgesia has remained elusive. Numerous studies have accumulated that polymodal nociceptive C-fibres play a crucial role in the generation and conduction of pain signals and sensitization of which following injury or inflammation leads to marked hyperalgesia. Traditionally, the number of nociceptive primary afferent firings is believed to be determined at the free nerve endings, while the extended main axon of unmyelinated C-fibres only involves the reliable and faithful propagation of firing series to the central terminals. We challenged this classic view by showing that conduction of action potential can fail to occur in response to repetitive activity when they travel down the main axon of polymodal nociceptive C-fibres. Quantitative analysis of conduction failure revealed that the degree of conduction failure displays a frequency-dependent manner. Local administration of low threshold, rapidly activating potassium current blocker, α-dendrotoxin (0.5 nM) and persistent sodium current blocker, low doses of tetrodotoxin (nociceptive C-fibres. Following streptozotocin-induced diabetes, a subset of polymodal nociceptive C-fibres exhibited high-firing-frequency to suprathreshold mechanical stimulation, which account for about one-third of the whole population of polymodal nociceptive C-fibres tested. These high-firing-frequency polymodal nociceptive C-fibres in rats with diabetes displayed a marked reduction of conduction failure. Delivery of low concentrations of tetrodotoxin and Nav1.8 selective blocker, A-803467 on the main axon of C-fibres was found to markedly enhance the conduction failure in a dose-dependent manner in diabetic rats. Upregulated expression of sodium

  20. Optical coherence tomography study of experimental anterior ischemic optic neuropathy and histologic confirmation.

    Science.gov (United States)

    Ho, Joyce K; Stanford, Madison P; Shariati, Mohammad A; Dalal, Roopa; Liao, Yaping Joyce

    2013-09-05

    The optic nerve is part of the central nervous system, and interruption of this pathway due to ischemia typically results in optic atrophy and loss of retinal ganglion cells. In this study, we assessed in vivo retinal changes following murine anterior ischemic optic neuropathy (AION) by using spectral-domain optical coherence tomography (SD-OCT) and compared these anatomic measurements to that of histology. We induced ischemia at the optic disc via laser-activated photochemical thrombosis, performed serial SD-OCT and manual segmentation of the retinal layers to measure the ganglion cell complex (GCC) and total retinal thickness, and correlated these measurements with that of histology. There was impaired perfusion and leakage at the optic disc on fluorescein angiography immediately after AION and severe swelling and distortion of the peripapillary retina on day-1. We used SD-OCT to quantify the changes in retinal thickness following experimental AION, which revealed significant thickening of the GCC on day-1 after ischemia followed by gradual thinning that plateaued by week-3. Thickness of the peripapillary sensory retina was also increased on day-1 and thinned chronically. This pattern of acute retinal swelling and chronic thinning on SD-OCT correlated well with changes seen in histology and corresponded to loss of retinal ganglion layer cells after ischemia. This was a serial SD-OCT quantification of acute and chronic changes following experimental AION, which revealed changes in the GCC similar to that of human AION, but over a time frame of weeks rather than months.

  1. Intraepidermal nerve-fibre density as a biomarker of the course of neuropathy in patients with Type 2 diabetes mellitus.

    Science.gov (United States)

    Divisova, S; Vlckova, E; Srotova, I; Kincova, S; Skorna, M; Dusek, L; Dubovy, P; Bednarik, J

    2016-05-01

    This paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus. Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P 2.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control. The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy. © 2015 Diabetes UK.

  2. Striated muscle fiber size, composition and capillary density in diabetes in relation to neuropathy and muscle strength

    DEFF Research Database (Denmark)

    Andreassen, Christer Swan; Jensen, Jacob Malte; Jakobsen, Johannes

    2014-01-01

    study was to evaluate histologic properties and capillarization of diabetic skeletal muscle in relation to DPN and muscle strength. METHODS: Twenty type 1 and 20 type 2 diabetic (T1D and T2D, respectively) patients underwent biopsy of the gastrocnemic muscle, isokinetic dynamometry at the ankle......, electrophysiological studies, clinical examination, and quantitative sensory examinations. Muscle biopsies were stained immunohistochemically and muscle fiber diameter, fiber type distribution, and capillary density determined. Twenty control subjects were also included in the study. RESULTS: No relationship was found...... between muscle fiber diameter, muscle fiber type distribution, or capillary density and degree of neuropathy or muscle strength for either patient group. Muscle fiber diameter and the proportion of Type II fibers were greater for T1D patients than both T2D patients and controls. The T2D patients had fewer...

  3. Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

    Science.gov (United States)

    Arnold, Lesley M; McCarberg, Bill H; Clair, Andrew G; Whalen, Ed; Thomas, Neal; Jorga, Anamaria; Pauer, Lynne; Vissing, Richard; Park, Peter W

    2017-11-01

    The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.

  4. Diabetic neuropathy enhances voltage-activated Ca2+ channel activity and its control by M4 muscarinic receptors in primary sensory neurons.

    Science.gov (United States)

    Cao, Xue-Hong; Byun, Hee Sun; Chen, Shao-Rui; Pan, Hui-Lin

    2011-11-01

    Painful neuropathy is one of the most serious complications of diabetes and remains difficult to treat. The muscarinic acetylcholine receptor (mAChR) agonists have a profound analgesic effect on painful diabetic neuropathy. Here we determined changes in T-type and high voltage-activated Ca(2+) channels (HVACCs) and their regulation by mAChRs in dorsal root ganglion (DRG) neurons in a rat model of diabetic neuropathy. The HVACC currents in large neurons, T-type currents in medium and large neurons, the percentage of small DRG neurons with T-type currents, and the Cav3.2 mRNA level were significantly increased in diabetic rats compared with those in control rats. The mAChR agonist oxotremorine-M significantly inhibited HVACCs in a greater proportion of DRG neurons with and without T-type currents in diabetic than in control rats. In contrast, oxotremorine-M had no effect on HVACCs in small and large neurons with T-type currents and in most medium neurons with T-type currents from control rats. The M(2) and M(4) antagonist himbacine abolished the effect of oxotremorine-M on HVACCs in both groups. The selective M(4) antagonist muscarinic toxin-3 caused a greater attenuation of the effect of oxotremorine-M on HVACCs in small and medium DRG neurons in diabetic than in control rats. Additionally, the mRNA and protein levels of M(4), but not M(2), in the DRG were significantly greater in diabetic than in control rats. Our findings suggest that diabetic neuropathy potentiates the activity of T-type and HVACCs in primary sensory neurons. M(4) mAChRs are up-regulated in DRG neurons and probably account for increased muscarinic analgesic effects in diabetic neuropathic pain. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  5. Metabolic neuropathies

    Science.gov (United States)

    Neuropathy - metabolic ... damage can be caused by many different things. Metabolic neuropathy may be caused by: A problem with ... is one of the most common causes of metabolic neuropathies. People who are at the highest risk ...

  6. Does footwear affect balance?: the views and experiences of people with diabetes and neuropathy who have fallen.

    Science.gov (United States)

    Paton, Joanne S; Roberts, Anne; Bruce, Graham K; Marsden, Jon

    2013-01-01

    Despite falls being a major concern for people living with somatosensory deficit, little is known about the perceived impact of footwear and footwear features on balance. Clinical relevance is increased given that therapeutic footwear is often provided to people with diabetes to reduce foot ulcer risk. This qualitative study aims to explore the experiences and views of people with diabetes and neuropathy who have recently fallen to understand whether footwear type is perceived to affect balance or contribute to falling. Sixteen individuals (13 men and three women aged 44-83 years) were purposively sampled from a larger population of potential participants. Audio-recorded, in-depth, semistructured interviews were conducted in participant homes or at a place preferable to them. Once transcribed verbatim, the data were themed, charted, and interpreted using a framework approach. Although most participants did not believe that the footwear in which they fell contributed to their fall, most revealed how footwear choice influenced their balance confidence to undertake daily tasks. Most found their therapeutic footwear "difficult" to walk in, "heavy, or "slippery bottomed." Design recommendations for enhanced balance included a close fit with tight fastening, lightweight, substantial tread, and a firm, molded sole/insole. Complying with these recommendations, the hiking sandal was believed to be the most stable and safe shoe and was frequently worn as a walking aid to reduce fear of falling and boost confidence. People with diabetic neuropathy have disease-specific needs and concerns relating to how footwear affects balance. Engaging with patients to address those needs and concerns is likely to improve the feasibility and acceptability of therapeutic footwear to reduce foot ulcer risk and boost balance confidence.

  7. Lower Physical Activity Is Associated With Higher Intermuscular Adipose Tissue in People With Type 2 Diabetes and Peripheral Neuropathy

    Science.gov (United States)

    Sinacore, David R.; Cade, W. Todd; Mueller, Michael J.

    2011-01-01

    Background Increased lipid accumulation in skeletal muscle has been linked to insulin resistance, impaired muscle performance, and impaired physical function. It is unclear whether physical activity is associated with lipid content in skeletal muscle, muscle performance, or overall physical function. Objective The purpose of this study was to characterize physical activity levels (average daily step count) in a sample of people with diabetes and peripheral neuropathy and to determine the relationship among step count, intermuscular adipose tissue volume (IMAT), muscle performance (peak torque, power), and physical function. Design A cross-sectional design was used in this study. Methods Twenty-two people with diabetes and peripheral neuropathy (15 men and 7 women, mean age=64.5 years [SD=12.7], and mean body mass index=33.2 kg/m2 [SD=6.4]) participated. Average daily step count, glycosylated hemoglobin, modified 9-item Physical Performance Test scores, Six-Minute Walk Test distance, calf intermuscular adipose tissue volume (via magnetic resonance imaging), and isokinetic dynamometry of the ankle muscles were recorded. Results Average daily step count was 7,754 (SD=4,678; range=3,088–20,079). Five participants had an average daily step count greater than 10,000. Average IMAT volume was 84 cm3 (SD=88). Greater average daily step count was associated with younger age (r=−.39, P<.05) and with lower IMAT volume in the calf (r=−.44, P<.05). Lower IMAT volume was associated with greater muscle performance (r=−.45) and physical function (r=−.43 to −.48). Limitations The sample in this study may be biased toward people with high levels of activity because participants were recruited for an exercise study. The results should not be generalized to people taking fewer than 3,000 steps/day or to those with a current foot ulcer, peripheral arterial disease, or severe foot deformity or amputation or who weigh more than 136 kg (300 lb). Conclusions Average daily step

  8. Plantar fascia enthesopathy is highly prevalent in diabetic patients without peripheral neuropathy and correlates with retinopathy and impaired kidney function.

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    Full Text Available Aim of this study was to evaluate the prevalence of plantar fascia (PF enthesopathy in Type 2 diabetes mellitus (T2DM patients without distal peripheral neuropathy (DPN.We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI. All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF.PF thickness was significantly higher in T2DM patients (p<0.0001. T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002, enthesophyte (p = 0.02 and cortical irregularity (p = 0.02. The overall sum of abnormalities was higher in T2DM patients (p<0.0001, as was the percentage of bilateral involvement (p = 0.005. In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05 and enthesophytes (OR 5.13, p = 0.001; reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04; body mass index (BMI predicted cortical irregularity (OR 0.87, p = 0.05; mean glucose predicted enthesophyte (OR 1.01, p = 0.03; LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02.Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.

  9. Prevalence and correlates of diabetic peripheral neuropathy in a Saudi Arabic population: a cross-sectional study.

    Science.gov (United States)

    Wang, Dong D; Bakhotmah, Balkees A; Hu, Frank B; Alzahrani, Hasan Ali

    2014-01-01

    The purpose of this cross-sectional study was to investigate the prevalence and correlates of diabetic peripheral neuropathy (DPN) in a Saudi population. The study population consisted of 552 diabetic participants with an average age of 53.4 years. Among this population, 62.7% were male and 94.9% had type 2 diabetes. The average body mass index was 31.1 kg/m2. DPN was diagnosed based on a combination of reduced vibration perception measured by neurothesiometer and/or reduced light touch perception evaluated by the 10-g Semmes-Weinstein monofilament, as well as neurological symptoms. Information on socio-demographic variables, smoking status, duration of diabetes, and medications was obtained through interviews by physicians. Body weight, height, waist circumference, blood pressure and clinical markers were assessed following standard procedures. The prevalence of DPN in this population was 19.9% (95% CI, 16.7%-23.5%). In the multivariable analyses, longer duration of diabetes [odds ratio (OR) for every 5-year increase, 2.49, 95% CI, 1.75-3.53], abdominal obesity (OR, 2.53, 95% CI, 1.41-4.55), and higher levels of fasting blood glucose (OR for every 1 mmol/L increase, 1.05, 95% CI, 0.99-1.12), creatinine (OR for every 10 µmol/L increase, 1.07, 95% CI, 0.99-1.14) and white blood cell count (OR for every 106/L increase, 1.08, 95% CI, 1.01-1.16) were associated with higher odds of DPN, while oral hypoglycemic medication use was associated with a lower odds of DPN (OR, 0.47, 95% CI, 0.26-0.85). In this large Saudi population, several correlates for DPN, in addition to glycemic control and diabetes duration, were identified, including abdominal obesity, creatinine and white blood cell count.

  10. Prevalence and correlates of diabetic peripheral neuropathy in a Saudi Arabic population: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Dong D Wang

    Full Text Available The purpose of this cross-sectional study was to investigate the prevalence and correlates of diabetic peripheral neuropathy (DPN in a Saudi population. The study population consisted of 552 diabetic participants with an average age of 53.4 years. Among this population, 62.7% were male and 94.9% had type 2 diabetes. The average body mass index was 31.1 kg/m2. DPN was diagnosed based on a combination of reduced vibration perception measured by neurothesiometer and/or reduced light touch perception evaluated by the 10-g Semmes-Weinstein monofilament, as well as neurological symptoms. Information on socio-demographic variables, smoking status, duration of diabetes, and medications was obtained through interviews by physicians. Body weight, height, waist circumference, blood pressure and clinical markers were assessed following standard procedures. The prevalence of DPN in this population was 19.9% (95% CI, 16.7%-23.5%. In the multivariable analyses, longer duration of diabetes [odds ratio (OR for every 5-year increase, 2.49, 95% CI, 1.75-3.53], abdominal obesity (OR, 2.53, 95% CI, 1.41-4.55, and higher levels of fasting blood glucose (OR for every 1 mmol/L increase, 1.05, 95% CI, 0.99-1.12, creatinine (OR for every 10 µmol/L increase, 1.07, 95% CI, 0.99-1.14 and white blood cell count (OR for every 106/L increase, 1.08, 95% CI, 1.01-1.16 were associated with higher odds of DPN, while oral hypoglycemic medication use was associated with a lower odds of DPN (OR, 0.47, 95% CI, 0.26-0.85. In this large Saudi population, several correlates for DPN, in addition to glycemic control and diabetes duration, were identified, including abdominal obesity, creatinine and white blood cell count.

  11. Diagnosis of diabetic neuropathy using simple somatic and a new autonomic (neuropad) tests in the clinical practice.

    Science.gov (United States)

    Kamenov, Z A; Petrova, J J; Christov, V G

    2010-04-01

    The global spread of diabetes (DM) and the importance of early therapeutic intervention determine the need of simple, inexpensive and sensitive methods for diagnosis of diabetic complications in the general practice. The aim of this study was to assess a new instrument - the plaster Neuropad in diagnosing the sudomotor diabetic dysfunction and to investigate the correlates of Neuropad data with diabetic complications. In this cross-sectional study participated 264 inpatients (M/F=126/138) with DM type 1/2 (61/203), mean age 55.4+/-12.0 and DM duration of 9.3+/-7.1 years. According to hospital records were registered: anthropometric data; fasting plasma glucose and HbA1c; presence of micro-(retino-, nephro-, neuropathy), and macrovascular (arterial hypertension, coronary artery disease and/or brain vascular disease) complications, and neuropathic symptoms were evaluated. For investigation of somatic DN a modified Neuropathy Disability Score (NDS) and for sudomotor autonomic DN - Neuropad were used. Neuropad showed the highest between-feet correlation of 0.91 compared to all other individual tests and the NDS. Neuropad was able to separate patients in groups with different general risk profile, including age, duration of DM, presence of coronary and/or brain vascular disease, nephropathy, and retinopathy. Moreover, Neuropad differentiated patient groups by their stage of DN, evaluated by symptoms, diagnosis, the individual somatic tests and with the highest significance - by NDS. Most sensitive for detecting DN was NDS > or = 3, followed by Achilles reflexes, vibration perception (128 Hz tuning fork) and Neuropad. A borderline or abnormal result of Neuropad showed sensitivity=76.3/79.3, specificity=56.1/42.9, positive=86.3/62.8 and negative=39.5/63.0 predictive values, and diagnostic accuracy 72.2/62.9%, compared to the indices for presence of somatic DN (NDS > or = 3)/foot at risk (NDS > or = 6) respectively. Screening for DN must cover somatic and autonomic

  12. {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 lung existed in patients with diabetes mellitus. The phenomenon might be related with sympathetic dysfunction or severity of diabetes mellitus. (author)

  13. 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.

  14. 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

    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...... offspring with parental type 2 diabetes (6.7%) was significantly (P pressure...... UAER, fasting insulin level, and 24-h AMBP and a reduced diurnal blood pressure variation. This study indicates that parental type 2 diabetes has an impact on the cardiac autonomic function in nondiabetic subjects....

  15. Comparison of peripheral nerve damages according to glucose control timing in experimental diabetes.

    Science.gov (United States)

    Jin, H Y; Kang, S M; Liu, W J; Song, C H; Lee, K A; Baek, H S; Park, T S

    2012-09-01

    In addition to tight glucose control, early intensive therapy has been reported to be more important for the prevention of diabetic micro- and macro-vascular complications. What is not known exactly is the quantitative difference according to timing delay in glucose control and whether early period control is really better than late control in terms of diabetic peripheral neuropathy. In this study, we investigated the effect of timing differences in glucose control on the peripheral nerves in an experimental diabetic model. 5 groups (6-8 rats in each group) were comprised of normal glucose rats (designated control), rats with hyperglycemia (designated DM), rats with glucose control for the entire 28-week study period (designated DM + INS [W0-28]), rats with glucose control for the early 14-week period followed by hyperglycemia for the late 14-week period (designated DM + INS [W0-14]), and rats with hyperglycemia for the early 14-week period followed by glucose control in the late 14-week period (designated DM + INS [W15-28]). We found that the current perception threshold (CPT) was lower in the DM + INS (W0-28) and DM + INS (W15-28) groups than in the DM + INS (W0-14) or DM groups (Pcontrol is necessary to alleviate peripheral nerve damage and that glycemic control during the later period may be more important than early period management. The importance of continuous glucose control, including the later period of diabetes, should therefore be emphasized in diabetic peripheral neuropathy. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  16. Nephrotic-like proteinuria in experimental diabetes.

    Science.gov (United States)

    Greive, Kerryn A; Osicka, Tanya M; Russo, Leileata M; Comper, Wayne D

    2003-01-01

    Streptozotocin (STZ) diabetic rats are characterized by the development of albuminuria. It is not known, however, whether the excess excretion of protein is primarily due to intact protein or protein fragments or whether it is specific for albumin or occurs for all high-molecular-weight plasma proteins. To test this we have measured the excretion rates and fractional clearances of [(14)C]albumin, [(3)H]immunoglobulin G and [(3)H]transferrin in diabetic rats. The radiolabeled proteins were delivered to the circulation of conscious diabetic (STZ induced for 6 weeks) and control rats by ALZET osmotic pumps. The plasma level of the radiolabeled proteins reached steady-state levels by day 7. Urine and plasma samples from day 7 were used to determine the excretion rates of the proteins by radioactivity and radioimmunoassay. When excretion rates were determined by radioactivity it was apparent that only the albumin excretion rate increased significantly with STZ diabetes to a value of 354 +/- 166 microg/min which agrees with proteinuria determined by Biuret assay of 299.9 +/- 52.4 microg/min. The major proportion of protein being excreted was in the form of protein fragments which are not detected by conventional immmunochemical assays. The previously unrecognized nephrotic-like levels of proteinuria in experimental diabetes appears to be associated with an albumin-specific mechanism responsible for the increase in albumin peptides in urine. There was significant lowering of plasma albumin concentration but plasma concentrations of transferrin and immunoglobulin G remained unchanged. There was also no significant appearance of intact protein in urine that is normally found in nephrotic states. Copyright 2003 S. Karger AG, Basel

  17. Impact of action cues, self-efficacy and perceived barriers on daily foot exam practice in type 2 diabetes mellitus patients with peripheral neuropathy.

    Science.gov (United States)

    Chin, Yen-Fan; Huang, Tzu-Ting; Hsu, Brend Ray-Sea

    2013-01-01

    To identify the effects of health belief model factors on daily foot-exam practice among diabetes mellitus patients with peripheral neuropathy. Daily foot exams are one of the most important self-care behaviours that prevent the occurrence of diabetic foot ulcers and subsequent amputation. Although daily foot exams were under-practiced in patients with peripheral neuropathy, few studies have explored modifiable social-psychological factors related to daily foot exams. A cross-sectional survey was used to collect the data. A total of 277 patients with diabetes and peripheral neuropathy were recruited from two hospitals in northern Taiwan. The Family APGAR and Diabetic Foot Ulcer Health Belief Scale (DFUHBS) were used to measure family support and health belief factors respectively. Data on foot-exam practice, perceived self-efficacy and action cues were collected through the use of structured questionnaires. The data were analysed using logistic regression. The regression model revealed that select action cues (recommendations from family, friends, or health professionals), perceived self-efficacy and perceived barriers interactively influenced the participants' daily foot-exam practice. Factors related to daily foot-exam practice were identified. Specifically, action cues played a significant role in motivating daily foot-exam practice in this group. This study recognises modifiable factors that influence the daily foot-exam practice of patients with diabetes and peripheral neuropathy. Using the findings of this study, health professionals can design interventions that aim to modify the above factors as a means to promote daily foot-exam practice. © 2012 Blackwell Publishing Ltd.

  18. Coenzyme Q10 and oxidative stress, the association with peripheral sensory neuropathy and cardiovascular disease in type 2 diabetes mellitus.

    Science.gov (United States)

    Forsberg, Elisabete; Xu, Cheng; Grünler, Jacob; Frostegård, Johan; Tekle, Michael; Brismar, Kerstin; Kärvestedt, Lars

    2015-01-01

    Our study aimed to explore associations between metabolic control, oxidative stress and coenzyme Q10 (CoQ10) in relation to diabetes complications in a representative population of type 2 diabetes. A geographic cohort of 156 subjects was recruited. Serum concentrations of CoQ10 and vitamin E were measured by HPLC. ROS was determined by free oxygen radicals testing (FORT). Glutaredoxin (Grx) activity, oxidized LDL cholesterol (oxLDLc), high sensitive CRP (hsCRP), HbA1c, urine albumin, serum creatinine, serum cystatin C, and plasma lipids were assayed with routine laboratory protocols. Serum CoQ10 was higher than in nondiabetics. HbA1c, fP-glucose, hyperlipidemia, inflammation (hsCRP), and increased BMI were associated with signs of oxidative stress as increased levels of FORT, Grx activity and/or increased levels of oxLDLc Oxidative stress was found to be strongly correlated with prevalence of cardiovascular disease (CVD) and peripheral sensory neuropathy (PSN). In both gender groups there were positive correlations between CoQ10 and oxLDLc, and between BMI and the ratio CoQ10/chol. Grx activity was inversely correlated to oxLDLc and CoQ10. Women with CVD and PSN had higher waist index, oxLDLc, and FORT levels compared to men but lower CoQ10 levels. Men had worse kidney function and lower vitamin E. Multiple regression analysis showed increased levels of CoQ10 to be significantly correlated with increased levels of cholesterol, triglycerides, vitamin E, fB-glucose and BMI. Hyperlipidemia, hyperglycemia and inflammation were associated with oxidative stress, which was correlated to the prevalence of diabetes complications. CoQ10 was increased in response to oxidative stress. There were gender differences in the risk factors associated with diabetes complications. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats.

    Directory of Open Access Journals (Sweden)

    Wei Yu

    Full Text Available Diabetic cardiomyopathy (DCM, characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved.An experimental diabetic rat model was induced by low dose of streptozoticin(STZ combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg · kg(-1 · d(-1, respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot.Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products accumulation and RAGE (receptor for AGEs expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP(+/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91(phox and p47(phox , raised inflammatory factor (TNF-α and IL-1β, enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL, diminished Akt and GSK-3β phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3β was also restored by curcumin treatment.Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt

  20. Oral Carnosine Supplementation Prevents Vascular Damage in Experimental Diabetic Retinopathy

    NARCIS (Netherlands)

    Pfister, Frederick; Riedl, Eva; Wang, Qian; vom Hagen, Franziska; Deinzer, Martina; Harmsen, Martin Conrad; Molema, Grietje; Yard, Benito; Feng, Yuxi; Hammes, Hans-Peter

    2011-01-01

    Backgrounds/Aims: Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic<