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1.
Life Sci ; 255: 117856, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473246

RESUMO

BACKGROUND: Ferulic acid (FA) is a phenolic phytochemical known to protect against various diabetic complications. However, its role in diabetic neuropathy is still unclear. The present study investigated the potential protective effects of FA alone and its combination with insulin against streptozotocin (STZ)-induced diabetic neuropathy in rats. METHODS: STZ (55 mg/kg) was injected in adult Sprague-Dawley rats to induce diabetes. Diabetic rats were treated with FA (25, 50, and 100 mg/kg, p.o), insulin (10 IU/kg, s.c.) and the combination of FA (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for four weeks. Body weight, blood glucose, insulin, glycosylated hemoglobin, nerve conduction velocity and pain parameters were measured. Moreover, oxidative stress, inflammatory (TNF-α, IL-1ß, COX-2) and apoptotic markers (Bcl-2, Bax, caspase 3) were assessed in the sciatic nerve tissue. Na+-K+-ATPase activity and nerve growth factor (NGF) levels were also determined. RESULTS: FA attenuated STZ induced alteration in metabolic parameters, nociceptive threshold, motor nerve conduction velocity, NGF levels and Na+-K+-ATPase activity. In addition, FA boosted anti-oxidant defenses and suppressed oxidative stress, pro-inflammatory mediators and apoptotic markers. Furthermore, diabetic rats treated with insulin-FA (100 mg/kg) combination demonstrated more pronounced beneficial effects as compared to either agent alone. CONCLUSIONS: Collectively, our results suggest that FA either alone or in combination with insulin therapy could serve as an efficacious agent for treating diabetic neuropathy.


Assuntos
Ácidos Cumáricos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Ácidos Cumáricos/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estreptozocina
2.
Medicine (Baltimore) ; 99(17): e19843, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332636

RESUMO

BACKGROUND: The most common and bothersome lower urinary tract complication of diabetes mellitus is diabetic neurogenic bladder (DNB). Acupuncture has certain advantages in treating bladder dysfunction including urinary retention and incontinence. Therefore, we think that electroacupuncture (EA) may be beneficial to DNB patients. However, it is not clear whether EA combined with basic western medicine could optimize the therapeutic effect for DNB. METHOD/DESIGN: This is a sham-controlled, patient-blinded, pioneer randomized controlled trial (RCT). One hundred fifty eligible patients will be randomly divided into 3 groups: A. basic western medicine (BWC), B. EA with BWC, C. sham EA with BWC. EA treatment will be given twice a week for 12 weeks at bilateral BL23, BL32, BL33, and BL35. The BWC group will received Alpha-lipoic acid (ALA) and methylcobalamin (MC) treatment for 12 weeks, 2 treatment sessions per week. The primary outcome is scored by the 72-hour bladder diary (72h-BD). The secondary outcomes will be scored by the American Urological Association symptom index (AUA-SI), Post-void residual urine volume (PVR) and urodynamic tests. All the assessments will be conducted at baseline and the 12th weeks after the intervention starts. The follow-up assessments will be performed with 72h-BD and AUA-SI in the 4th, 12th, and 24th weeks after intervention ends. DISCUSSION: This trial protocol provides an example of the clinical application acupuncture treatment in the management of DNB. This RCT will provide us information on the effect of treating DNB patients with only acupuncture, western medicine therapy (ALA + MC) as well as the combination of both. The additive effect or synergistic effect of acupuncture and basic western medicine will then be analyzed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030421.


Assuntos
Neuropatias Diabéticas/terapia , Eletroacupuntura , Bexiga Urinaria Neurogênica/terapia , Adolescente , Adulto , Idoso , Neuropatias Diabéticas/fisiopatologia , Eletroacupuntura/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Ácido Tióctico/uso terapêutico , Resultado do Tratamento , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologia , Urodinâmica , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto Jovem
3.
Nurse Pract ; 45(2): 24-31, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895251

RESUMO

Cardiac autonomic neuropathy (CAN) is an underdiagnosed cardiovascular complication associated with diabetes. NPs are in a pivotal position to screen patients for CAN. As the incidence of diabetes increases in an aging population, NPs can help prevent complications associated with diabetes and CAN.


Assuntos
Doenças do Sistema Nervoso Autônomo/enfermagem , Neuropatias Diabéticas/enfermagem , Cardiopatias/enfermagem , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Cardiopatias/fisiopatologia , Humanos , Programas de Rastreamento/enfermagem , Profissionais de Enfermagem , Diagnóstico de Enfermagem
4.
Eur J Pharmacol ; 866: 172835, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31794708

RESUMO

Diabetes mellitus is characterized by metabolic dysregulation associated with a number of health complications. More than 50% of patients with diabetes mellitus suffer from diabetic polyneuropathy, which involves the presence of peripheral nerve dysfunction symptoms. The aim of this study was to evaluate the potential of a new synthetic arginine-rich exendin-4 (Peptide D) in the treatment of complications caused by diabetes, including peripheral neuropathy, in rats. Diabetes was induced by administering streptozotocin (STZ). Three groups of diabetic rats were treated with Peptide D (0.1, 1, and 10 µg/kg). One group of diabetic rats was treated with Byetta® (1 µg/kg) for 80 days. Neuropathic pain development was assessed by tactile allodynia. STZ-treated rats showed an increased level of tactile allodynia unlike naïve animals. A histological study revealed that the diameter of the sciatic nerve fibers in STZ-treated rats was smaller than that of the naïve animals. An IHC study demonstrated decreased expression of myelin basic protein (MBP) in the sciatic nerve of diabetic rats compared to that in the naïve animals. Peptide D reduced the severity of tactile allodynia. This effect was more pronounced in the Peptide D treated groups than in the group treated with Byetta®. Peptide D and Byetta® treatment resulted in increased MBP expression in the sciatic nerve and increased diameter of myelinated nerve fibers. These findings suggest that poly-arginine peptides are promising agents for the treatment of peripheral polyneuropathies.


Assuntos
Arginina/química , Neuropatias Diabéticas/tratamento farmacológico , Exenatida/química , Exenatida/farmacologia , Animais , Glicemia/metabolismo , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Exenatida/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Hiperalgesia/complicações , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Locomoção/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia
5.
Muscle Nerve ; 61(1): 88-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614013

RESUMO

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Nervo Sural/fisiopatologia , Potenciais de Ação , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Axônios/patologia , Estudos Transversais , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Eletrodiagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Estudos Prospectivos , Células Receptoras Sensoriais
6.
BMC Endocr Disord ; 19(1): 125, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767009

RESUMO

BACKGROUND: Compositional abnormalities in lipoproteins and cardiovascular risk factors play an important role in the progression of diabetic peripheral neuropathy (DPN). This systematic review aimed to estimate the predicting value of low-density lipoprotein (LDL) and systolic blood pressure (SBP) level in type-2 diabetes mellitus (T2DM) patients with and without peripheral neuropathy. We also tried to determine whether LDL and SBP are associated with an increased collision risk of DPN. METHODS: A systematic search was conducted for eligible publications which explored the LDL and SBP level in T2DM patients with and without peripheral neuropathy. The quality of the included studies was assessed by the QUADAS-2 tool. The standardized mean difference (SMD) with 95% CI of LDL and SBP level were pooled to assess the correlation between LDL and SBP level with DPN. We performed random effects meta-regression analyses to investigate factors associated with an increased collision risk of DPN. RESULTS: There was a significant association between LDL and SBP with poor prognosis of DPN in those included studies (I2 = 88.1% and I2 = 84.9%, respectively, Both P < 0.001). European T2DM patients have higher serum level of LDL in compare with the European DPN patients (SMD = 0.16, 95% CI: - 0.06 - 0.38; P < 0.001). SBP level was associated with a 2.6-fold decrease in non-DPN patients of T2DM (SMD = - 2.63, 95% CI: - 4.00 - -1.27, P < 0.001). Old age European T2DM patients have significantly high risk for diabetes drivers. Furthermore, the results of the case-control study design model are more precise to show the accuracy of SBP in Asian T2DM patients. CONCLUSION: Our finding supports the LDL and SBP status could be associated with increased risk of peripheral neuropathy in T2DM patients.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/fisiopatologia , Lipoproteínas LDL/sangue , Sístole , Estudos de Casos e Controles , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/etiologia , Humanos , Estudos Observacionais como Assunto , Prognóstico
7.
Med Arch ; 73(4): 262-267, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31762562

RESUMO

Introduction: Complications on the lower extremities are a major cause of morbidity, disability, emotional and physical suffering in people with diabetes. Diabetic neuropathy (DN) is the most frequent complication of both types of diabetes. Lack of performance of the musculoskeletal system of lower leg and foot can results in high focal plantar pressures with increased ulceration risk in patients with neuropathy. Aim: To determine the impact of the severity of distal symmetric polyneuropathy (DSPN) on the foot and ankle muscle strength and the range of motion (ROM) at ankle joint (AJ), subtalar joint (SJ) and first metatarsophalangeal joint (I MTP). Methods: A cross-sectional study was conducted among 100 diabetic patients. The level of DSPN was assessed using the Neuropathy Disability Score. Function of ten foot and ankle muscles has been evaluated by manual muscle testing. Muscle strength was scored by semiquantitative grading system used in the Michigan Diabetic Neuropathy Score. ROM at the AJ, SJ and I MTP was measured with goniometer. Results: The average patients age was 61.91±10.74 and diabetes duration 12.25±8.60 years. DSPN was present in 45% of patients. The average strength of foot and ankle muscles expressed by muscle score was 11.56±5.08. The average ROM at AJ was 47.85°, at SJ 35.10° and at I MTP 72.70°. Correlations between the severity of the DSPN and muscle function, ROM at AJ, SJ and I MTP were statistically significant. ROM at SJ and I MTP declines significantly with progression of neuropathy but not significant at AJ. Conclusion: The severity of DSPN is significantly associated with foot and ankle muscle weakness and ROM at the SJ and the I MTP, but not significantly with the ROM at the AJ.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Pé/fisiopatologia , Perna (Membro)/fisiopatologia , Estudos Transversais , Neuropatias Diabéticas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Amplitude de Movimento Articular , Índice de Gravidade de Doença
8.
Adv Skin Wound Care ; 32(12): 568-573, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31764147

RESUMO

OBJECTIVE: To determine the effect of an intervention involving muscular ankle strengthening and feet sensory stimuli to improve gait speed and balance in older adults with diabetes mellitus type 2 (DM2). DESIGN: A clinical trial with concealed allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: The trial enrolled 66 people 60 years or older with DM2 who were physically independent (did not require assistance with activities of daily living). INTERVENTION: The experimental group performed 12 weeks of plantiflexor and dorsiflexor muscle strengthening exercises with resistance bands, proprioceptive exercises on balance boards and a buoy, and plantar sensory stimulation with bristle brushes and cloths, as well as general foot care instructions. The control group received foot care instructions only. OUTCOME MEASURES: The primary outcome was plantar cutaneous sensibility as measured with Semmes-Weinstein monofilaments. Secondary outcomes included muscular strength (plantar flexion and dorsiflexion torque as measured with an isokinetic dynamometer), gait speed, and balance (total displacement area, mediolateral displacement, anteroposterior displacement, mediolateral displacement speed, and anteroposterior displacement speed) on right and left bipedal and unipedal supports. RESULTS: In comparison with the control group, the experimental group demonstrated improved plantar cutaneous sensibility on the right foot (3.46 points; 95% confidence interval [CI], 3.85-9.80), left foot (3.46 points; 95% CI, 4.06-9.76), and an increase in gait speed (0.15 m/s; 95% CI 0.12-0.42). There were no meaningful changes in participants' ankle muscle strength or balance. CONCLUSIONS: This study showed that plantar cutaneous sensory stimulation can improve foot sensibility and increase the gait speed of older adults with DM2. However, there were no meaningful dorsiflexor or plantiflexor gains after 12 weeks.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/terapia , Terapia por Exercício/métodos , Força Muscular/fisiologia , Estimulação Física/métodos , Atividades Cotidianas , Idoso , Intervalos de Confiança , Neuropatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Índice de Gravidade de Doença , Resultado do Tratamento , Velocidade de Caminhada
9.
Adv Exp Med Biol ; 1190: 345-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760655

RESUMO

Schwann cells maintain peripheral nerve structure and function by ensheathment of unmyelinated axons, myelination of myelinated axons, and secretion of neurotrophic factors, and these cells also play a crucial role in the pathogenic mechanisms of diabetic neuropathy. A decrease in unmyelinated and small myelinated axons appeared earlier than a decrease in large myelinated fibers in diabetic neuropathy. Electron microscopic studies of human diabetic neuropathy demonstrated edematous cell cytoplasm, aggregates of glycogen particles, and hyperplasia of the surrounding basal lamina in Schwann cells. Diabetic conditions also induces metabolic disorders, such as polyol pathway hyperactivity, activation of protein kinase C, and increased advanced glycosylation end products in Schwann cells, followed by the depletion of neurotrophic factor production.Cell transplantation using progenitor or stem cells is expected to cure diabetic neuropathy. Many studies demonstrated that the paracrine effect of abundant secreted factors from transplanted stem cells was crucial for the success of cell transplantation in diabetic neuropathy. Transplantation of progenitor or stem cells in diabetic animal models ameliorated impaired nerve conduction velocity, nerve blood flow, sensory disorders, and intraepidermal nerve fiber density, with an increase of myelin thickness. The supernatant from cultured dental pulp stem cells increased the proliferation and production of myelin-related protein in Schwann cells, suggesting that Schwann cells is the main target of cell transplantation for diabetic neuropathy.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Bainha de Mielina/patologia , Células de Schwann/patologia , Animais , Axônios/patologia , Neuropatias Diabéticas/terapia , Modelos Animais de Doenças , Humanos , Nervos Periféricos , Transplante de Células-Tronco
10.
J Diabetes Res ; 2019: 1973704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781661

RESUMO

Background: Shear is a major risk factor in the development of diabetic foot ulcers, but its effect on the skin of patients with type 2 diabetes mellitus (DM) remains to be elucidated. The aim was to determine skin responses to shear in DM patients with and without diabetic polyneuropathy (DNP). Methods: The forearm skin was loaded with 14.5 N shear (+2.4 kPa pressure) and with 3.5 kPa pressure for 30 minutes in 10 type 2 DM patients without DNP, 10 type 2 DM patients with DNP, and 10 healthy participants. A Sebutape collected IL-1α (measure of tissue damage). A laser Doppler flowmeter measured cutaneous blood cell flux (CBF) as a measure of the reactive hyperaemic skin response. Findings: Reactive hyperaemia and IL-1α release was significantly increased after shear loading in all three groups and was higher compared to the responses to pressure loading. The reactive hyperaemic response after shear loading was impaired in patients with type 2 DM compared to healthy participants but did not differ between patients with and without DNP. The reactive hyperaemic response was negatively correlated with the blood glucose level but did not correlate with the DNP severity score. Interpretation: Shear is important in the development of tissue damage, but the reparative responses to shear are impaired in patients with type 2 DM. DNP was not associated with altered skin responses, suggesting that the loss of protective sensation to sense shear to skin remains a key factor in the development of diabetic foot ulcers in patients with DNP.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Hemodinâmica , Microcirculação , Úlcera Cutânea/etiologia , Pele/irrigação sanguínea , Adulto , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Feminino , Antebraço , Humanos , Hiperemia/fisiopatologia , Interleucina-1alfa/metabolismo , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Fatores de Risco , Pele/metabolismo , Pele/patologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/metabolismo , Úlcera Cutânea/fisiopatologia , Estresse Mecânico , Sobrevivência de Tecidos
11.
Exp Brain Res ; 237(12): 3165-3174, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586215

RESUMO

This study aims to investigate the impact of type 2 diabetes (T2D) and diabetic peripheral neuropathy (DPN) on pinch proprioception and to establish the correlations with sensory impairments. We collected data from a total of 36 participants (healthy, n = 12; T2D without DPN, n = 11; and T2D + DPN, n = 13), all matched for age, 60 ± 6 years. Pinch proprioception was determined through 3 trials of attempts to actively reproduce 15° of pinch position without visual feedback. Target accuracy and precision was compared between groups using Kruskal-Wallis test. Sensation was tested through the two-point discrimination and Semmes-Weinstein monofilaments applied on the fingers. Sensory measures were correlated with pinch proprioception measures via Spearman's rank test. The T2D + DPN group showed significant decrements in accuracy and precision as compared to the T2D-only (p = 0.003 and p = 0.006, respectively) and the healthy groups (both p = 0.002); no significant differences were found between T2D-only and healthy. Spearman's rank showed moderate (r = 0.45-0.66, p < 0.001) correlations between pinch proprioception and sensory measures. Our results showed pinch proprioception disruption in people with T2D + DPN, but not in people with T2D-only. The awareness of pinch proprioceptive deficits is paramount for the safety of individuals with T2D and DPN. Moderate correlations between sensory impairments and pinch proprioceptive deficits suggest that not only superficial/discriminative sensation is implicated in proprioceptive decrements. Other mechanisms such as damage to muscle spindles or central nervous system associated with T2D + DPN warrant further investigations.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Atividade Motora/fisiologia , Força de Pinça/fisiologia , Propriocepção/fisiologia , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Feminino , Dedos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Diabetes Res ; 2019: 5020465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485451

RESUMO

Aims: Determine the effect of dietary oils enriched in different mono- or polyunsaturated fatty acids, i.e., olive oil (18 : 1, oleic acid), safflower oil (18 : 2 n-6, linoleic acid), flaxseed oil (18 : 3 n-3, alpha linolenic acid), evening primrose oil (18 : 3 n-6, gamma linolenic acid), or menhaden oil (20:5/22 : 6 n-3 eicosapentaenoic/docosahexaenoic acids), on vascular and neural complications in high-fat-fed low-dose streptozotocin-treated Sprague-Dawley rats, an animal model for late-stage type 2 diabetes. Materials and Methods: Rats were fed a high-fat diet (45% kcal as fat primarily derived from lard) for 8 weeks and then treated with a low dose of streptozotocin (30 mg/kg) in order to induce hyperglycemia. After an additional 8 (early intervention) or 20 (late intervention) weeks, the different groups of rats were fed diets with 1/2 of the kcal of fat derived from lard replaced by the different dietary oils. In addition, a control group fed a standard diet (4.25% kcal as fat) and a diabetic group maintained on the high-fat diet were maintained. The treatment period was approximately 16 weeks. The endpoints evaluated included vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, thermal and corneal sensitivity, and innervation of sensory nerves in the cornea and skin. Results: Our findings show that menhaden and flaxseed oil provided the greatest benefit for correcting peripheral nerve damage caused by diabetes, whereas enriching the high-fat diet with menhaden oil provided the most benefit to acetylcholine-mediated vascular relaxation of epineurial arterioles of the sciatic nerve. Enriching the diets with fatty acids derived from the other oils provided none to partial improvements. Conclusions: These studies imply that long-chain n-6 and n-3 polyunsaturated fatty acids could be an effective treatment for diabetic peripheral neuropathy with n-3 polyunsaturated fatty acids derived from fish oil being the most effective.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Angiopatias Diabéticas/dietoterapia , Neuropatias Diabéticas/dietoterapia , Gorduras Insaturadas na Dieta/administração & dosagem , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Dieta Hiperlipídica , Gorduras Insaturadas na Dieta/farmacologia , Esquema de Medicação , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiopatologia , Estreptozocina , Fatores de Tempo
13.
Diabetes Res Clin Pract ; 156: 107844, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31520713

RESUMO

AIMS: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). METHODS: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. RESULTS: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). CONCLUSIONS: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Coração/fisiopatologia , Nervos Periféricos/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Gait Posture ; 74: 194-199, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31550557

RESUMO

BACKGROUND: The control of foot trajectory during swing phase is important to achieve safe clearance with the ground. Complexity of a physiological control system arises from the interaction of structural units and regulatory feedback loops that operate to enable the organism to adapt to a non-static environment. Diabetic polyneuropathy (DPN) impairs peripheral feedback inputs and alters ankle control during gait, which might affect toe clearance (ToC) parameters and its complexity, predisposing DPN-subjects to tripping and falling. RESEARCH QUESTION: How do different DPN-severity degrees change ToC trajectory and minimum ToC, and its complexity during gait of diabetic subjects? METHODS: 15 healthy controls and 69 diabetic subjects were assessed and classified into DPN-severity degrees by an expert fuzzy model: absent (n = 26), mild (n = 21) and severe (n = 22). Three-dimensional kinematics was measured during comfortable walking. ToC was the minimum vertical distance between the marker placed at the first metatarsal head and the ground during swing. Mean ToC, ToC standard deviation (SD) between trials, and sample entropy (SaEn) and standard deviation (SD) of ToC trajectory were calculated from the ToC temporal series. ANOVA and ANCOVA (with the walking speed as the covariate) and Bonferroni pairwise post-hoc tests (P < 0.05) were used to compare groups. RESULTS: Mean ToC and ToC SD did not show differences between groups (ANCOVA F = 0.436; df = 3; P = 0.705; F=1.719; df=3; P=0.170, respectively). ToC trajectory SD also did not show differences between groups (ANCOVA F = 3.98; df = 3; P = 0.755). Severe-DPN subjects showed higher ToC_Traj_SaEn than controls (ANCOVA F=2.60; df=3; P = 0.05). SIGNIFICANCE: Severe-DPN subjects showed a more complex pattern of overall foot-ankle trajectory in swing phase in comparison to controls, although did not present lower minimum ToC values. The higher complexity of ToC might lead to an increase in the motor system output (more strategies, increase in variability), resulting in a more unstable system and selected motor strategies.


Assuntos
Diabetes Mellitus/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Pé/fisiologia , Marcha/fisiologia , Caminhada/fisiologia , Adulto , Idoso , Análise de Variância , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Diabetes ; 68(11): 2143-2154, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31492662

RESUMO

While peripheral neuropathy is the most common complication of long-term diabetes, cognitive deficits associated with encephalopathy and myelopathy also occur. Diabetes is a risk factor for Alzheimer disease (AD) and increases the risk of progression from mild cognitive impairment to AD. The only current recommendation for preventing or slowing the progression of peripheral neuropathy is to maintain close glycemic control, while there is no recommendation for central nervous system disorders. NSI-189 is a new chemical entity that when orally administered promotes neurogenesis in the adult hippocampus, increases hippocampal volume, enhances synaptic plasticity, and reduces cognitive dysfunction. To establish the potential for impact on peripheral neuropathy, we first showed that NSI-189 enhances neurite outgrowth and mitochondrial functions in cultured adult rat primary sensory neurons. Oral delivery of NSI-189 to murine models of type 1 (female) and type 2 (male) diabetes prevented multiple functional and structural indices of small and large fiber peripheral neuropathy, increased hippocampal neurogenesis, synaptic markers and volume, and protected long-term memory. NSI-189 also halted progression of established peripheral and central neuropathy. NSI-189, which is currently in clinical trials for treatment of major depressive disorder, offers the opportunity for the development of a single therapeutic agent against multiple indices of central and peripheral neuropathy.


Assuntos
Aminopiridinas/uso terapêutico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Piperazinas/uso terapêutico , Células Receptoras Sensoriais/efeitos dos fármacos , Aminopiridinas/farmacologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/fisiopatologia , Feminino , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Piperazinas/farmacologia , Ratos , Sinapses/efeitos dos fármacos
16.
Gait Posture ; 74: 114-120, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499405

RESUMO

PURPOSE: The aim of the study was to evaluate the effect of sensorimotor training on balance measures, and proprioception, among middle-aged and older adults with diabetic peripheral neuropathy (DPN). METHODS: A randomized controlled study with four parallel arms (two intervention groups and two control groups) was conducted at CPRS, Jamia Millia Islamia. Thirty-seven individuals were selected on the basis of inclusion and exclusion criteria. Of these, 16 middle-aged and 21 older adults were randomly allocated to intervention and control groups, respectively. Subjects in the intervention group were administered eight weeks (3days/week) of sensorimotor training, involving 10 different types of exercises, progressed from easy to hard every two weeks, along with diabetes and foot care education; subjects in control group received diabetes and foot care education only. Outcomes measures involved static and dynamic balance measures, centre of pressure (COP) range, COP sway, and proprioception, measured before and after eight weeks. RESULTS: Baseline measures showed significant age effect for timed up and go test (TUG) (p =  0.002), one leg stance (OLS) in eyes open (EO) and eyes closed (EC) (p ≤ 0.041), COP range in front (p =  0.007), back (p =  0.009) and right direction (p =  0.013), COP sway with visual feedback in front-back direction (p =  0.027), COP sway without visual feedback in left-right direction (p =  0.028), and proprioception in right direction (p =  0.026). After intervention, OLS EO and EC on both legs showed significant time effect (p ≤  0.003), group effect as well as time×group interaction (p <  0.05), and age effect and time×age interaction (p ≤  0.04). Functional reach test, TUG, COP range, COP sway, and proprioception were found with significant time effect (p <  0.03), group effect, and time×group interaction (p ≤  0.035). Age effect and time×age interaction were found to be non-significant for all COP ranges and COP sway. CONCLUSION: Sensorimotor training improved static and dynamic balance as well as proprioception measures after eight weeks of exercise intervention. Static balance showed greater improvement in the middle-aged than older aged adults, while dynamic balance and proprioception showed similar results for both.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Terapia por Exercício/métodos , Transtornos Neurológicos da Marcha/fisiopatologia , Modalidades de Fisioterapia , Equilíbrio Postural/fisiologia , Propriocepção/fisiologia , Idoso , Análise de Variância , Retroalimentação Sensorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Tempo e Movimento
17.
Clin Neurophysiol ; 130(10): 1981-1987, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476704

RESUMO

OBJECTIVE: Detection of motor involvement in diabetic polyneuropathy (DPN) by nerve conduction studies (NCS) does not occur until there is substantial loss of motor units, because collateral reinnervation maintains compound muscle action potential (CMAP) amplitude. Motor unit number estimation (MUNE) methods may therefore be more sensitive. This study was undertaken to test whether the novel method, MScanFit MUNE (MScan) can detect motor involvement in DPN despite normal NCS. METHODS: Fifty-two type-2 diabetic patients and 38 healthy controls were included. The median nerve was examined in all participants using standard NCS and a detailed CMAP scan, used for MScan. Additional lower extremity NCS in patients were used for DPN diagnosis. RESULTS: Of 52 diabetic patients, 21 had NCS-defined DPN while lower extremity NCS were normal in 31 patients. MScan motor unit number and size showed higher sensitivity and incidence of abnormality than motor NCS parameters, and a similar sensitivity to sensory NCS. CONCLUSIONS: MScan is able to detect motor axonal damage at times when collateral reinnervation limits NCS changes. SIGNIFICANCE: MScan is a sensitive method to detect motor involvement in DPN, which our data suggests is present as early as sensory.


Assuntos
Potenciais de Ação/fisiologia , Neuropatias Diabéticas/fisiopatologia , Neurônios Motores/fisiologia , Condução Nervosa/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia
18.
J Diabetes Res ; 2019: 7395769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380446

RESUMO

The abnormal plantar pressure distribution and value play a key role in the formation of plantar calluses and diabetic foot ulcer. The prevalence of the highest pressure different distribution and its association with various factors among patients with diabetes is not well known. The study purpose was to evaluate the prevalence of different regions for the highest pressure on the sole and its association with selected factors among patients with diabetes. Medical records of nonulcer patients were retrospectively analysed. The relationship between pressure patterns on the sole obtained during a pedobarographic test as a semiquantitative assessment with colourful print analysis and neuropathy, gender, age, and BMI was searched. The most common location of the highest pressure was the central part of the forefoot. No association was found between the different highest pressure regions and age, sensory neuropathy, calluses, and foot deformities. The highest pressure on the lateral part of the foot and midfoot was observed more often in females and in patients with a BMI ≥ 35. The prevalence of the highest pressure on the forefoot was more common in patients with a BMI < 35. Conclusions. The most frequent regions of the highest pressure on the sole in patients with diabetes were the central part of the forefoot (2-3 metatarsal heads) with no simple relationship to the assessed variables other than BMI < 35. Female gender and higher BMI seem to be responsible for shifting the place of the highest pressure to other places of the foot.


Assuntos
Diabetes Mellitus/fisiopatologia , Neuropatias Diabéticas/epidemiologia , Deformidades Adquiridas do Pé/fisiopatologia , Pé/fisiologia , Pressão , Caminhada/fisiologia , Idoso , Calo Ósseo/fisiopatologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Pé Diabético/complicações , Pé Diabético/epidemiologia , Pé Diabético/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Deformidades Adquiridas do Pé/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ortopedia/métodos , Estudos Retrospectivos
19.
Endocrinology ; 160(9): 2119-2127, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318414

RESUMO

Worldwide, the most prevalent metabolic disorder is diabetes mellitus (DM), an important condition that has been widely studied. Diabetic peripheral neuropathy (DPN), a complication that can occur with DM, is associated with pain and can result in foot ulcers and even amputation. DPN treatments are limited and mainly focus on pain management. There is a clear need to develop treatments for DPN at all stages. To make this progress, it is necessary to understand the molecular signaling pathways related to DPN. For this review, we aimed to concentrate on the main signaling cascades that contribute to DPN. In addition, we provide information with regard to treatments that are being explored.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Transdução de Sinais/fisiologia , Animais , Neuropatias Diabéticas/fisiopatologia , Dislipidemias/complicações , Glicosilação , Humanos , Fatores de Crescimento Neural/fisiologia , Estresse Oxidativo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Proteína Quinase C/fisiologia
20.
J Diabetes Res ; 2019: 2435261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355291

RESUMO

Diabetic peripheral neuropathy (DPN) involves sensory and motor nerves, resulting in demyelination as well as axonal degeneration. This study was conducted to describe the pattern of lower limb nerve involvement in children with type 1 diabetes mellitus (DM) based on the parameters of nerve conduction study (NCS). This cross-sectional study recruited 50 children with type 1 DM having mean disease duration of 4.92 ± 3.84 years who attended the referred clinic in Sudan Childhood Diabetes Center. Their mean age was 15.00 ± 2.19 years, 42% were males, and 58% were females. Twenty six matched healthy control subjects were involved; their mean age was 13.88 ± 2.46 years, 38.46% were males, and 61.54% were females. Bilateral NCS of the sensory and motor lower limb nerves was performed using Medelec Synergy machine. Interpretation of the patients' results was based on our own control reference values. Data was analysed using IBM SPSS statistics. Out of the 50 diabetic patients, 44 (88%) had electrophysiological evidence of peripheral neuropathy (abnormalities in at least two of the electrophysiological parameters). The majority (68.2%) had motor involvement and 31.8% had sensorimotor, while none of them (0%) had pure sensory involvement. Regarding abnormal NCS parameters (conduction velocity vs. amplitude of the compound action potential), conduction slowing feature predominated in 61.4% and only few (6.8%) showed amplitude reduction, while 31.8% showed mixed features. The most frequently affected nerve was the common peroneal, followed by posterior tibial, and the least was the sural nerve. The most sensitive parameter was the common peroneal conduction velocity. Motor precedes sensory nerve involvement. The most frequent neurophysiological abnormality was the conduction slowing, and the common peroneal was the most vulnerable nerve. These findings signify generation of a protocol for early screening of neuropathy in children with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/fisiopatologia , Potenciais de Ação , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Condução Nervosa , Nervo Fibular/fisiopatologia , Sudão/epidemiologia , Nervo Tibial/fisiopatologia
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