Monotherapy Versus Combination Therapy in the Treatment of Painful Diabetic Neuropathy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy. METHODS: PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool. RESULTS: A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy. CONCLUSION: In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.

Papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético / Role of Diabetic Neuropathy in the Onset and Development of Diabetic Foot Syndrome

Introducción: La neuropatía diabética es la complicación más frecuente de la diabetes mellitus y una de sus posibles consecuencias es el síndrome del pie diabético. Los médicos del primer nivel de atención deben conocer el comportamiento clínico de la neuropatía diabética y, sobre todo, como influye en la aparición y desarrollo del síndrome del pie diabético. Objetivo: Describir el papel de la neuropatía diabética en la aparición y desarrollo del síndrome del pie diabético. Métodos: Para la obtención de la información se utilizaron como motores de búsqueda de información científica los correspondientes a Scielo, Pubmed, y Google Académico. Se usaron como palabras clave: diabetes mellitus; neuropatía diabética; pie diabético; síndrome de pie diabético; úlcera de pie diabético; ataque de pie diabético. Se evaluaron diferentes trabajos de revisión, investigación y páginas web, y se excluyeron los artículos que tuvieran más de 10 años de publicados, en idiomas diferentes al español, portugués e inglés y que no se refirieran al tema de estudio a través del título. Esto permitió la cita de 45 referencias bibliográficas. Conclusiones: La neuropatía diabética constituye el principal factor de riesgo en la aparición y desarrollo del síndrome del pie diabético, sobre todo cuando se asocia a artropatía (defectos podálicos), enfermedad vascular periférica y/o sepsis. El control de la glucemia, la detección temprana del pie de riesgo y el cuidado preventivo de los miembros inferiores, repercutirá favorablemente en la salud y bienestar del paciente(AU)

Introduction: Diabetic neuropathy is the most frequent complication of diabetes mellitus and one of its possible consequences is diabetic foot syndrome. First level of care physicians should know the clinical behavior of diabetic neuropathy and, above all, how it influences the appearance and development of diabetic foot syndrome. Objective: To describe the role of diabetic neuropathy in the appearance and development of diabetic foot syndrome. Methods: To obtain the information, SciELO, PubMed and Google Scholar were used as search engines for scientific information. The keywords used were: diabetes mellitus; diabetic neuropathy; diabetic foot; diabetic foot syndrome; diabetic foot ulcer; diabetic foot attack. Different review papers, research papers and web pages were evaluated and articles that were more than 10 years old and published in languages other than Spanish, Portuguese and English and that did not refer to the subject of the study through the title were excluded. This allowed the citation of 45 bibliographic references. Conclusions: Diabetic neuropathy constitutes the main risk factor in the appearance and development of diabetic foot syndrome, especially when associated with arthropathy (foot defects), peripheral vascular disease and/or sepsis. Glycemic control, early detection of the foot at risk and preventive care of the lower limbs will have a favorable impact on the patient's health and well-being(AU)

Polineuropatia diabética assintomática induzida pelo uso crônico de metformina e correlação com vitamina B12 / Asymptomatic diabetic polyneuropathy induced by chronic metformin use and correlation with vitamin B12

Introdução: Diabetes Mellitus é doença metabólica, caracterizada pela deficiência absoluta ou relativa de insulina, que acomete cerca de 382 milhões de pessoas em todo mundo, tendo uma das complicações mais comuns a polineuropatia. A Metformina, medicamento amplamente utilizado como tratamento do Diabetes, foi descrita como responsável, em algumas literaturas, por causar ou agravar deficiência de vitamina B12, que está similarmente relacionada ao desenvolvimento de polineuropatia.Métodos: Nesse sentido, foi conduzido um estudo no município de Soledade ­ RS, com objetivo de verificar se essa relação é condizente com a realidade da localidade. Foram escolhidos 58 pacientes, dos quais 30 responderam questionários adaptados baseados na literatura e na Classificação de Neuropatia de Michigan (MNSS-Brasil), então colhidos 5 ml de sangue venoso da fossa antecubital, preparado soro do qual uma alíquota foi separada para determinação bioquímica da vitamina B12.Resultados: Analisando os resultados, a maioria dos pacientes analisados apresentou sintomas de polineuropatia, e 10% deste, deficiência vitamínica.Conclusão: nenhuma variável explicou a correlação do uso crônico da Metformina, dose e gênero com a deficiência da vitamina B12, o que indica que não há evidências fortes o suficiente que sustentem esse fato, de acordo com as particularidades da localidade analisada.

Introduction: Diabetes Mellitus is a metabolic disease, characterized by absolute or relative insulin deficiency, which affects about 382 million people, with polyneuropathy being one of the most common complications. Metformin, a drug widely used as a treatment for diabetes, has been described as responsible, in some literature, for causing or aggravating vitamin B12 deficiency, which is similarly related to the development of polyneuropathy.Methods: In this sense, a study was conducted in Soledade ­ RS, in order to verify whether this relationship is consistent with the reality of the locality. Fifty-eight patients were selected, of which 30 answered adapted questionnaires based on the literature and on the Michigan Neuropathy Classification (MNSS-Brazil), then 5 ml of venous blood was collected from the antecubital fossa, serum prepared from which an aliquot was separated for biochemical determination of the vitamin B12.Results: Analyzing the results, most of these patients presented symptoms of polyneuropathy and, 10% of them, vitamin deficiency.Conclusion: no variable explained the correlation of chronic use of Metformin, dose and gender with vitamin B12 deficiency, which indicates that there is not enough evidence to support this fact, according to the particularities of the analyzed locality.

Exame do pé diabético: fatores de risco de ulceração em pacientes com diabetes mellitus / Examen del pie diabético: factores de riesgo de ulceración en pacientes con diabetes mellitus / Diabetic foot exam: risk factors of ulceration in patients with diabetes mellitus

Objetivo: descrever a evolução dos fatores de risco para o desenvolvimento de úlceras nos pés de pacientes com DM, em três exames subsequentes num período de 3 anos, num centro de especialidades médicas. Método: estudo descritivo, retrospectivo e longitudinal, com 102 pacientes, entre os anos de 2016 e 2019, que realizaram três exames dos pés sequenciais, fundamentado no padrão estabelecido pelo consenso internacional do pé diabético, sendo eles avaliação neuropática, vascular, dermatológica e uso dos calçados, coletado do Sistema do Pé Diabético. Resultados: 86,27% dos pacientes declararam sintomas neuropáticos, principalmente queimação, dormência e formigamento. A maioria hipertensos (74,71%) e idosos (67,65%), desses 13,73% com infarto prévio e 72,55% eram do sexo feminino. Do primeiro ao terceiro exame, o "risco muito baixo" aumentou 7,84% e "risco baixo" 8,83%, já o "risco elevado" reduziu 17,65%. Conclusão: a realização sistemática do exame clínico dos pés, associado a estratégias educativas efetivas, resultam num controle mais eficaz do risco de ulceração.

Objetivo: Describir la evolución de los factores de riesgo para el desarrollo de úlceras en los pies de pacientes con DM, en tres exámenes subsecuentes en un período de 3 años, en un centro de especialidades médicas. Método: estudio descriptivo, retrospectivo y longitudinal, con 102 pacientes, entre los años 2016 y 2019, que realizaron tres exámenes de los pies secuenciales, fundamentado en el patrón establecido por el consenso internacional del pie diabético, siendo ellos evaluación neuropática, vascular, dermatológica y uso de calzado, recogido del Sistema del Pie Diabético. Resultados: 86,27% de los pacientes declararon síntomas neuropáticos, principalmente ardor, entumecimiento y hormigueo. La mayoría hipertensos (74,71%) y ancianos (67,65%), de esos 13,73% con infarto previo y 72,55% eran mujeres. Del primero al tercer examen, el "riesgo muy bajo" aumentó un 7,84% y "riesgo bajo" un 8,83%, mientras que el "riesgo alto" redujo un 17,65%. Conclusión: la realización sistemática del examen clínico de los pies, asociado a estrategias educativas efectivas, resultan en un control más eficaz del riesgo de ulceración.

Objective: to describe the evolution of risk factors for the development of foot ulcers in patients with DM, in three subsequent exams over a period of 3 years, in a medical specialty center. Method: a descriptive, retrospective and longitudinal study, with 102 patients, between the years 2016 and 2019, who performed three sequential foot exams, based on the standard established by the international consensus of the diabetic foot, being use of footwear, collected from the Diabetic Foot System. Results: 86.27% of patients reported neuropathic symptoms, mainly burning, numbness and tingling. Most were hypertensive (74.71%) and elderly (67.65%), of these, 13.73% had previous infarction and 72.55% were female. From the first to the third examination, the "very low risk" increased 7.84% and the "low risk" 8.83%, while the "high risk" reduced 17.65%. Conclusion: the systematic clinical feet exam, associated with effective educational strategies, results in a more effective control of the risk of ulceration.

The PPARγ agonist pioglitazone produces a female-predominant inhibition of hyperalgesia associated with surgical incision, peripheral nerve injury, and painful diabetic neuropathy.

Pioglitazone, an agonist at peroxisome proliferator-activated receptor gamma, is FDA-approved for the treatment of insulin resistance in type 2 diabetes. Numerous studies in male rodents suggest that pioglitazone inhibits inflammatory and neuropathic pain, but few included female subjects. To address this gap, we compared the effects of pioglitazone in both sexes in the intraplantar methylglyoxal model (MG) model of chemical pain and painful diabetic neuropathy (PDN), the plantar incision model (PIM) of postoperative pain, the spared nerve injury (SNI) model of traumatic nerve injury, and the ZDF rat and db/db mouse models of PDN. We administered pioglitazone by one-time intrathecal or intraperitoneal injection or by adding it to chow for 6 weeks, followed by measurement of hypersensitivity to non-noxious mechanical, noxious mechanical, heat, and/or cold stimuli. In all mouse models, injection of pioglitazone decreased pain-like behaviors with greater potency and/or efficacy in females as compared to males: heat and mechanical hypersensitivity in the MG model (0.1-10 mg/kg); mechanical hypersensitivity in the PIM model (10 µg); mechanical and cold hypersensitivity in the SNI model (100 mg/kg); and heat hypersensitivity in the db/db model (100 mg/kg). Furthermore, co-administration of low doses of morphine (1 mg/kg) and pioglitazone (10 mg/kg) decreased SNI-induced mechanical and cold hypersensitivity in female but not male mice. In the ZDF rat, pioglitazone (100 mg/kg) decreased heat and mechanical hypersensitivity with no sex difference. In the db/db model, pioglitazone had no effect when given into chow for 6 weeks at 0.3, 3 or 30 mg/kg doses. We conclude that females exhibit greater anti-hyperalgesic responses to pioglitazone in mouse models of chemical-induced nociception, postsurgical pain, neuropathic pain, and PDN. These findings set the stage for clinical trials to determine whether pioglitazone has analgesic properties across a broad spectrum of chronic pain conditions, particularly in women.

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. OBJECTIVE: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. METHODS: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. RESULTS: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. CONCLUSION: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Maior frequência de neuropatia periférica diabética associada ao hiperparatireoidismo secundário / Higher prevalence of diabetic peripheral neuropathy associated with secondary hyperparathyroidism

INTRODUÇÃO: A neuropatia periférica diabética (ND) é comum na nefropatia diabética (NFD) e não há informações se o hiperparatireoidismo secundário (HPS) aumenta seus sintomas. O objetivo foi determinar ND por sinais em pacientes com HPS. MATERIAL E MÉTODOS: É um estudo caso-controle. O Grupo Controle (GC) é composto por doentes com NFD e valores de paratormônio (PTH)<60pg / ml. O Grupo de Hiperparatireoidismo (GH) engloba pacientes com NFD e PTH≥60pg/ml e critérios bioquímicos de HPS. As variáveis foram, entre outras, a presença de sinais de ND e foram comparados com o teste t de Student e o qui-quadrado. RESULTADOS: Foram 60 participantes em cada grupo, sendo 35 (58,3%) homens no GC vs 33 (55,0%) em GH (p = 0,713). A idade do GC foi de 67±11,0 anos, vs 72±11 anos GH (p=0,009). A taxa de filtração glomerular (TFG) no GC foi 53,82±25,13 vs GH 35,34±18,43ml/min/1,73m2 (p <0,001). O PTH no GC foi de 38,02±15,32 pg/ml, em GH 119,07±84,33 pg/ml (p <0,001). A ND, devido aos sintomas no GC, foi de 28,3% e 36,6% no GH (p=0,330). A neuropatia por sinais no GC foi de 38,3% e no GH 83,3% (p<0,001). O odds ratio de GH para neuropatia presente devido a sinais foi de 8,044 (IC 95% 3,42­8,92). CONCLUSÃO: Constatou-se uma maior presença de sinais de NPD em pacientes com HPS em nosso centro.

BACKGROUND: Diabetic peripheral neuropathy (DN) is common in diabetic nephropathy (DNP), and there is no information if secondary hyperparathyroidism (SHP) increases its symptoms. The purpose was to determine DN by signs in patients with SHP. METHODS: It is a case-control study. Control patients (CG) with DN and parathyroid hormone (PTH) values<60pg/ml. The Hyperparathyroidism group (HG), patients with DNP and PTH≥60pg/ml and HPS biochemical criteria. The variables were, among others, the presence of DN signs, and were compared with Student's t and chi-square. RESULTS: There were 60 participants in each group, 35(58.3%) men in CG vs.33(55.0%) in GH (p=0.713). The age of the CG was 67±11.0 years, vs 72±11years HG (p=0.009). The glomerular filtration rate (GFR) in the CG was 53.82±25.13 vs in HG 35.34±18.43ml/min/1.73m2(p<0.001). The PTH in the CG were 38.02±15.32pg/ml and in GH 119.07±84.33pg/ml(p<0.001). The DN due to symptoms in CG was 28.3% and in GH 36.6%(p=0.330). Neuropathy due to signs in the CG was 38.3% and in GH 83.3% (p<0.001). The HG odds ratio to present neuropathy due to signs was 8.044 (95% CI 3.42­18.92). CONCLUSION: There was a statistical association between HPS and signs of DN in patients with DNP in our canter.

Correlates of diabetic polyneuropathy of the elderly in Sub-Saharan Africa.

BACKGROUND: Diabetic polyneuropathy is associated with significant physical disability among older adults. However, their frequency and correlates are not well known in the older adults in Sub-Saharan-Africa. The objectives were to evaluate the hospital-based prevalence of diabetic polyneuropathy and identify its correlates in older adults. METHODS: Over a period of 5 months, a cross-sectional survey was carried out at Douala Laquintinie Hospital (DLH), a main reference hospital in Douala, the economic capital of Cameroon. Participants in our study group comprised all patients with type 2 diabetes, whatever the reason for their reporting to the hospital. Diabetic Polyneuropathy was defined according to a Diabetic Neuropathy Examination score > 3/16. RESULTS: A total of 159 older adults with diabetes were examined during this recruitment period, among whom 106 (66.7%) were women. The mean age was 68.3 ± 6.5 years. Diabetes median duration was 108 months. For all patients assessed using the Diabetic Neuropathy Examination score, polyneuropathy was reported in 31.4%; among them, polyneuropathy proved symptomatic in 78% of them. Correlates of polyneuropathy were glycated hemoglobin (p = 0.049), HIV infection (p = 0.031) and albuminuria (p< 0.001), even after adjustment for age, gender and duration of diabetes. CONCLUSION: A third of older adults with diabetes who visited our hospital were diagnosed with prevalent diabetes-related polyneuropathy. It shows that early detection is required through routine screening and regular follow-up examinations in order to reduce the risk of disability and improve the quality of life in elderly diabetics.

Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System.

Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations-no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125-25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy.

Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study.

The paucity of epidemiological data regarding diabetes complications in Brazil motivated us to evaluate the prevalence rates of distal symmetric polyneuropathy (DSP) and of cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes (T2D) followed in a primary care unit. A total of 551 individuals (59.3% women, 65 years old; diabetes duration of 10 years; HbA1c of 7.2%, medians) were included in this cross-sectional study. DSP was diagnosed by sum of the Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score (NDS) and by the Semmes-Weinstein monofilament. CAN was diagnosed by cardiovascular autonomic reflex tests combined with spectral analysis of heart rate variability. The prevalence rates of DSP were 6.3% and 14.3%, as evaluated by the sum of NSS and NDS and by the Semmes-Weinstein monofilament, respectively. Those with DSP diagnosed by monofilament presented longer diabetes duration, worse glycemic control and a higher stature. The prevalence rates of incipient and definitive CAN were 12.5% and 10%, respectively. Individuals with definitive CAN presented a higher frequency of hypercholesterolemia and of arterial hypertension. The higher prevalence rate of DSP with the use of the monofilament suggests that it may be a more appropriate tool to diagnose DSP in the primary care setting in Brazil.

The prevalence of peripheral neuropathy severe enough to cause a loss of protective sensation in a population-based sample of people with known and newly detected diabetes in Barbados: a cross-sectional study.

AIMS: To determine the prevalence and potential risk factors for diabetic peripheral neuropathy with a loss of protective sensation in Barbados. METHODS: A representative population sample aged > 25 years with previously diagnosed diabetes or a fasting blood glucose ≥ 7 mmol/l or HbA1c ≥ 48 mmol/mol (6.5%) was tested by 10 g monofilament at four plantar sites per foot and a 28 Hz tuning fork and neurothesiometer at the hallux. Data were adjusted to the age structure of people with diabetes in Barbados. Multivariable logistic regression assessed associations with peripheral neuropathy with a loss of protective sensation. RESULTS: Of 236 participants [74% response rate, 33% men, 91% black, median age 58.6 years, mean BMI 30.1 kg/m2 , mean HbA1c 54 mmol/mol (7.1%)], 51% had previously diagnosed diabetes. Foot examination demonstrated that 25.8% (95% CI 20.2 to 31.5) had at least one insensate site with monofilament testing, 14.8% (95% CI 10.2 to 19.4) had an abnormal tuning fork test and 10.9% (95% CI 6.9 to 14.9) had a vibration perception threshold > 25 V. Peripheral neuropathy with a loss of protective sensation prevalence was 28.5% (95% CI 22.7 to 34.4) as indicated by monofilament with ≥ 1 insensate site and/or vibration perception threshold > 25 V. With previously diagnosed diabetes the prevalence was 36.4% (95% CI 27.7 to 45.2) with 98.4% of cases identified by monofilament testing. Increasing age, previously diagnosed diabetes, male sex and abdominal obesity were independently associated with peripheral neuropathy with a loss of protective sensation. CONCLUSIONS: Over a third of people with previously diagnosed diabetes had evidence of peripheral neuropathy with a loss of protective sensation. Monofilament testing alone may be adequate to rule out peripheral neuropathy with a loss of protective sensation. Monofilament and neurothesiometer stimuli are reproducible but dependent on participant response.

α5GABAA receptors play a pronociceptive role and avoid the rate-dependent depression of the Hoffmann reflex in diabetic neuropathic pain and reduce primary afferent excitability.

Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. However, the role of extrasynaptic α5 subunit-containing GABAA (α5GABAA) receptors in this process is not known. The purpose of this study was to investigate the role of α5GABAA receptors in diabetes-induced tactile allodynia, loss of rate-dependent depression (RDD) of the Hoffmann reflex (HR), and modulation of primary afferent excitability. Intraperitoneal administration of streptozotocin induced tactile allodynia. Intrathecal injection of α5GABAA receptor inverse agonist, L-655,708, produced tactile allodynia in naive rats, whereas it reduced allodynia in diabetic rats. In healthy rats, electrical stimulation of the tibial nerve at 5 Hz induced RDD of the HR, although intrathecal treatment with L-655,708 (15 nmol) abolished RDD of the HR. Streptozotocin induced the loss of RDD of the HR, while intrathecal L-655,708 (15 nmol) restored RDD of the HR. L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4 to L6 dorsal root ganglion. Streptozotocin increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4 to L6 dorsal root ganglia in 10-week diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively, and are tonically active in primary afferents.

Comparative study on laser and LED influence on tissue repair and improvement of neuropathic symptoms during the treatment of diabetic ulcers.

To compare the influence of laser and LED on tissue repair and neuropathic symptoms during treatment of diabetic foot. An intervention survey conducted in a health center located in Brazil, contemplating ten sessions, twice a week, with randomization in two groups. In one group, the wounds were treated with GaAlAs laser, with a wavelength of 830 nm, 30 mW, and power density 0.84 W/cm2, the other group by LED 850 nm, 48 mW, and power density 1.05 W/cm2. For the analysis of wound size, photographic records analyzed by the ImageJ® software were used, and the neuropathy evaluation card examined. With regard to the laser group, a reduction in wound extension of 79.43% was observed at the end of the 10th session; the patients in the LED group had a 55.84% decrease in the healing process; comparing the two therapies was observed a better healing in the participants of the laser group, with 81.17%, in relation to the LED after the end of the sessions; regarding the evaluation of the neuropathic condition, there was a significant improvement in both therapies. There was improvement of the neuropathic signs and symptoms, also improvement of the tissue repair in the two therapeutic modalities; however, the laser presented a higher rate of speed in relation to the LED.

Interleukin-1beta in synergism gabapentin with tramadol in murine model of diabetic neuropathy.

Neuropathic pain is a complication of cancer and diabetes mellitus and the most commonly used drugs in the treatment of the diabetic neuropathic pain have only limited efficacy. The aim of this study was to evaluate the role of the biomarker interleukin-1beta (IL-1ß) in the pharmacological interaction of gabapentin with tramadol in a model of diabetic neuropathic pain. CF-1 male mice, pretreated with 200 mg/kg i.p. of streptozocin (STZ), were used and at day 3 and 7 were evaluated by the hot plate test and the spinal cord level of IL-1ß was determined. Antinociceptive interaction of the coadministration i.p. of gabapentin with tramadol, in basic of the fixed the ratio 1:1 of their ED50 values alone, was ascertained by isobolographic analysis. Tramadol was 1.13 times more potent than gabapentin in saline control mice, 1.40 times in STZ mice at 3 days and 1.28 times in STZ at 7 days. The interaction between gabapentin and tramadol was synergic, with an interaction index of 0.30 and 0.22 for mice pretreated with STZ at 3 and 7 days. The combination of gabapentin with tramadol reversed the increased concentration of IL-1ß induced by STZ in diabetic neuropathic mice. These findings could help clarify the mechanism of diabetic neuropathy.

Degree of risk for foot ulcer due to diabetes: nursing assessment.

OBJECTIVE: To classify the level of risk for foot ulcers in people with diabetes mellitus and identify their main predictive risk factors. METHOD: Exploratory, descriptive study, in which patients were assessed in a municipal ambulatory of São Paulo through nursing consultation, following the guidelines of the International Consensus on the Diabetic Foot. Data were descriptively analyzed. RESULTS: The analyzed population was composed of 50 longevous and retired people, with household income of up to two minimum wages, with dermato-neurofunctional risk factors and unfavorable clinical indicators, and 66% had Risk 1; 16% Risk 2; 6% Risk 3 and 12% Risk 4. Of this analyzed total, 96% never had their feet examined with the Semmes-Weinstein monofilament. CONCLUSION: The data found indicate the importance of careful feet examination in people with diabetes by the nursing staff to identify future risks of ulcers and, thus, prevent them.

Degree of risk for foot ulcer due to diabetes: nursing assessment / Grado de riesgo para las úlceras en los pies por diabetes: evaluación de enfermería / Grau de risco para úlceras nos pés por diabetes: avaliação de enfermagem

ABSTRACT Objective: To classify the level of risk for foot ulcers in people with diabetes mellitus and identify their main predictive risk factors. Method: Exploratory, descriptive study, in which patients were assessed in a municipal ambulatory of São Paulo through nursing consultation, following the guidelines of the International Consensus on the Diabetic Foot. Data were descriptively analyzed. Results: The analyzed population was composed of 50 longevous and retired people, with household income of up to two minimum wages, with dermato-neurofunctional risk factors and unfavorable clinical indicators, and 66% had Risk 1; 16% Risk 2; 6% Risk 3 and 12% Risk 4. Of this analyzed total, 96% never had their feet examined with the Semmes-Weinstein monofilament. Conclusion: The data found indicate the importance of careful feet examination in people with diabetes by the nursing staff to identify future risks of ulcers and, thus, prevent them.

RESUMEN Objetivo: Clasificar el grado de riesgo para las ulceraciones en los pies de las personas con diabetes mellitus e identificar sus principales factores de riesgo predictivos. Método: Estudio exploratorio, descriptivo, en el cual los pacientes fueron evaluados en un ambulatorio municipal de São Paulo por medio de la consulta de enfermería, según las directrices del International Consensus on the Diabetic Foot. Los datos fueron analizados descriptivamente. Resultados: La población analizada fue de 50 personas, longevos jóvenes, jubilados, con ingresos familiares de hasta dos salarios mínimos, con factores de riesgo dermato-neurofuncionales e indicadores clínicos desfavorables, siendo que el 66% presentó riesgo 1; el 16% de riesgo 2; el 6% riesgo 3; y el 12% de riesgo 4. De ese total analizado, el 96% nunca tuvo los pies examinados con el monofilamento de Semmes-Weinstein. Conclusión: Los datos encontrados apuntan la importancia de la evaluación cuidadosa de los pies de las personas con diabetes por la enfermería para identificar los riesgos futuros de ulceraciones y, de esta forma, prevenirlos.

RESUMO Objetivo: Classificar o grau de risco para ulcerações nos pés de pessoas com diabetes mellitus e identificar seus principais fatores de risco preditivos. Método: Estudo exploratório, descritivo, onde os pacientes foram avaliados em um ambulatório municipal de São Paulo por meio da consulta de enfermagem, segundo diretrizes do International Consensus on the Diabetic Foot. Os dados foram analisados descritivamente. Resultados: a população analisada foi de 50 pessoas, longevos jovens, aposentados, renda familiar de até dois salários mínimos, com fatores de risco dermato-neuro-funcionais e indicadores clínicos desfavoráveis, sendo que 66% apresentaram risco 1; 16% risco 2; 6% risco 3 e 12% risco 4. Dentre estes, 96% nunca tiveram seus pés examinados com o monofilamento de Semmes Weinstein. Conclusão: Os dados encontrados apontam a importância da avaliação criteriosa dos pés das pessoas com diabetes pela enfermagem para identificar os riscos futuros de ulcerações, e desta forma trabalhar a prevenção dos mesmos.

Caracterización del riesgo de presentar pie diabético. Servicio Provincial de Angiología de Matanzas. 2014-2015 / Characterization of the risk of developing diabetic foot. Provincial Service of Angiology of Matanzas. 2014-2015

RESUMEN Introducción: la identificación del pie en riesgo de las personas con diabetes permite su estratificación como paso previo para establecimiento de futuras estrategias preventivas para evitar la aparición de la úlcera del pie diabético. Objetivo: caracterizar el riesgo de presentar el pie diabético en los pacientes ingresados con esta afección en el Servicio Provincial de Angiología y Cirugía Vascular de Matanzas, entre septiembre 2014 y mayo 2015. Materiales y métodos: se realizó una investigación descriptiva, retrospectiva de corte transversal. La muestra de estudio estuvo constituida por 111 pacientes hospitalizados con diagnóstico de pie diabético en el Servicio Provincial de Angiología y Cirugía Vascular de Matanzas, en el periodo comprendido desde septiembre 2014 hasta mayo 2015. Resultados: en la estratificación del riesgo, predominaron los diabéticos con pie de riesgo 4, el uso de calzado inadecuado y el deficiente cuidado de los pies fueron los factores de riesgo relacionados con la educación del diabético que predominaron; la neuropatía diabética fue la condición más frecuente en los pacientes con pie de riesgo; sin embargo, las deformidades podálicas y la ausencia de pulsos periféricos también estuvieron presentes en un porciento elevado de los pacientes. Conclusiones: constituyeron riesgo para desarrollar un pie diabético: la neuropatía, el antecedente de úlcera y/o amputación, uso de calzado inadecuado y el deficiente cuidado de los pies (AU).

ABSTRACT Introduction: the identification of the foot at risk of people with diabetes allows its stratification as a preliminary step for the establishment of future preventive strategies to prevent the onset of the diabetic foot ulcer. Objective: to characterize the risk of developing diabetic foot in patients who entered the Provincial Service of Angiology and Vascular Surgery of Matanzas with this affection from September 2014 until May 2015. Material and method: a descriptive, retrospective, cross-sectional research was carried out. The studied sample was constituted by 111 hospitalized patients diagnosed with diabetic foot in the Provincial Service of Angiology and Vascular Surgery of Matanzas, in the period from September 2014 to May 2015. Results: in the stratification of risk, diabetic patients with risk 4 foot prevailed; the use of inadequate footwear and deficient feet care were the predominant risk factors related to the education of the diabetic patients; diabetic neuropathy was the most frequent condition in patients with compromised foot; however, podalic deformities and the absence of peripheral pulses were also present in a high percentage of patients. Conclusions: neuropathy, the antecedent of ulcer and / or amputation, the use of inadequate footwear and deficient care of the feet represent risk to develop a diabetic foot (AU).

Quadriceps muscle architecture ultrasonography of individuals with type 2 diabetes: Reliability and applicability.

Muscle architecture parameters performed using ultrasound serve as an aid to monitor muscle changes derived from diseases, however there are no studies that determine the reliability and applicability of this evaluation in individuals with type 2 diabetes (DM2). Three raters captured three images of measurements of thickness of the rectus femoris (RF), vastus intermedius and anterior quadriceps, RF muscle cross-sectional area, RF pennation angle in 17 individuals with DM2 above 50 and sedentary. Intra and inter-raters analysis showed reliability from high to very high for the three raters (ICC> 0.87), except for the RF pennation angle with moderate to low intra-raters (ICC = 0.58, 0.48, 0.51), and high inter-rater reliability (ICC = 0.70). Ultrasound measurements of quadriceps muscles showed high to very high intra and inter-raters reliability, thus allowing its use to monitor muscle changes provoked by diabetes or interventions in individuals with DM2.

[Frequency and associated risk factors of cardiovascular autonomic neuropathy among patients with type 2 Diabetes.] / Frecuencia y factores de riesgo asociados de Neuropatía Autonómica Cardíaca en pacientes con Diabetes tipo 2.

Background: Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes and is associated with cardiovascular morbidity and mortality. Despite its prevalence, it is usually underdiagnosed. Objective to assess frequency of CAN in type 2 diabetes, treated at the Diabetology Service at Cordoba Hospital, Argentina. Method: Cross-sectional study was conducted from May 2015 to May 2016. Cardiovascular Autonomic Tests (Ewing´s battery) were performed: response to Valsalva maneuver, expiration-to-inspiration ratio (E/I ratio), standing to lying flat and postural hypotension. Results: 100 type 2 diabetes patients, 53% females. The mean age and diabetes duration 52 years old and 8.4 years, respectively. Hemoglobin A1c level of 8.7% and 47% were insulin-requiring type 2 diabetes patients. 29% had early CAN, 54% confirmed CAN (10% severe CAN) and 17% normal cardiovascular tests. Confirmed CAN was higher in those with longer duration of diabetes; longer duration of insulin therapy, older patients and severe hypoglycemia events was higher in those with confirmed CAN versus without CAN or early CAN (p 0.003). The risk factors associated were hypertension OR 2.55 (p 0.02), peripheral neuropathy OR 11.7 (p <0.0001), diabetic retinopathy OR 9.03 (p 0.001), diabetic nephropathy OR 3.12 (p 0.03) and hemoglobin A1c > 7% OR 2.57 (p 0, 03). Conclusions: frequency of CAN was high, was associated with hypertension, microvascular complications, older age, poor metabolic control, longer duration of disease and insulin therapy. Patients with a higher risk of developing CAN should be identified, in order to reduce the impact of this complication.

Introducción: La neuropatía autonómica cardíaca (NAC) es una complicación frecuente de la diabetes y aumenta la morbimortalidad cardiovascular. A pesar de su prevalencia e impacto está subdiagnosticada. Objetivo: Determinar la frecuencia de NAC y factores de riesgo asociados en pacientes con diabetes tipo 2(DM2), en el Servicio de Diabetología del Hospital Córdoba. Material y Métodos: estudio transversal, desde Mayo de 2015 a Mayo de 2016. Se realizó Test Autonómicos Cardiovasculares: Maniobra de Valsalva (MV), Respiración Profunda (RP), Razón 30/15 e Hipotensión ortostática. Resultados: Se reclutaron 100 pacientes con DM2. 53 % sexo femenino. Edad promedio 52 años, IMC 30,9; HbA1c 8,7 % y evolución de la enfermedad 8,4 años. El 17 % presentaron test normales. El 29 % tenía NAC temprana y 54% NAC confirmada (10 % NAC severa). Los pacientes con NAC confirmada tenían mayor tiempo de evolución (11 vs 5 años ), mayor duración de insulinoterapia (5 vs 1,5 años ), mayor edad ( 54 vs 49 años ) y mayor riesgo de hipoglucemias severas comparado con pacientes sin NAC o NAC temprana (p 0,003).Factores de riesgo asociados hipertensión arterial OR 2,55 (p 0,02), neuropatía periférica OR 11,7 (p<0,0001) , retinopatía OR 9,03 (p 0,001), nefropatía OR 3,12 (p 0,03) y HbA1c > 7% OR 2,57(p 0,03). Conclusiones: Hubo una alta frecuencia de NAC, se asoció con hipertensión, complicaciones microvasculares, mayor edad, duración de la enfermedad, de la insulinoterapia y mal control metabólico. Se debería identificar a pacientes con mayor riesgo, para reducir su aparición e impacto.

Caracterización del riesgo de presentar pie diabético. Servicio Provincial de Angiología de Matanzas. 2014-2015 / Characterization of the risk of developing diabetic foot. Provincial Service of Angiology of Matanzas. 2014-2015

RESUMEN Introducción: la identificación del pie en riesgo de las personas con diabetes permite su estratificación como paso previo para establecimiento de futuras estrategias preventivas para evitar la aparición de la úlcera del pie diabético. Objetivo: caracterizar el riesgo de presentar el pie diabético en los pacientes ingresados con esta afección en el Servicio Provincial de Angiología y Cirugía Vascular de Matanzas, entre septiembre 2014 y mayo 2015. Materiales y métodos: se realizó una investigación descriptiva, retrospectiva de corte transversal. La muestra de estudio estuvo constituida por 111 pacientes hospitalizados con diagnóstico de pie diabético en el Servicio Provincial de Angiología y Cirugía Vascular de Matanzas, en el periodo comprendido desde septiembre 2014 hasta mayo 2015. Resultados: en la estratificación del riesgo, predominaron los diabéticos con pie de riesgo 4, el uso de calzado inadecuado y el deficiente cuidado de los pies fueron los factores de riesgo relacionados con la educación del diabético que predominaron; la neuropatía diabética fue la condición más frecuente en los pacientes con pie de riesgo; sin embargo, las deformidades podálicas y la ausencia de pulsos periféricos también estuvieron presentes en un porciento elevado de los pacientes. Conclusiones: constituyeron riesgo para desarrollar un pie diabético: la neuropatía, el antecedente de úlcera y/o amputación, uso de calzado inadecuado y el deficiente cuidado de los pies (AU).

ABSTRACT Introduction: the identification of the foot at risk of people with diabetes allows its stratification as a preliminary step for the establishment of future preventive strategies to prevent the onset of the diabetic foot ulcer. Objective: to characterize the risk of developing diabetic foot in patients who entered the Provincial Service of Angiology and Vascular Surgery of Matanzas with this affection from September 2014 until May 2015. Material and method: a descriptive, retrospective, cross-sectional research was carried out. The studied sample was constituted by 111 hospitalized patients diagnosed with diabetic foot in the Provincial Service of Angiology and Vascular Surgery of Matanzas, in the period from September 2014 to May 2015. Results: in the stratification of risk, diabetic patients with risk 4 foot prevailed; the use of inadequate footwear and deficient feet care were the predominant risk factors related to the education of the diabetic patients; diabetic neuropathy was the most frequent condition in patients with compromised foot; however, podalic deformities and the absence of peripheral pulses were also present in a high percentage of patients. Conclusions: neuropathy, the antecedent of ulcer and / or amputation, the use of inadequate footwear and deficient care of the feet represent risk to develop a diabetic foot (AU).