Efeito da suplementação de altas doses de vitamina D sobre a neuropatia autonômica cardiovascular em pacientes com diabetes mellitus tipo 1

Cardiovascular autonomic neuropathy (CAN), associated with diabetes mellitus (DM), despite being a subclinical condition, is an important morbidity and mortality factor in these patients. In type 1 diabetes mellitus (DM1) CAN is so alarming that it must be screened after the first 5 years of illness. Few therapeutic measures are recommended in international guidelines on the subject. Some authors have been studying drugs that can modified natural history of disease and then improve outcomes. Vitamin D seems promising resource and low cost. The aim of our study was to evaluate the effects of high-dose vitamin D (DV) supplementation on CAN in patients with DM1. We performed a prospective, interventional study in which 17 patients diagnosed with DM1 and CAN were included. Patients with VD levels below 30 ng / mL received 10,000 IU / day, and when 30-60 ng / mL, they used 4,000 IU / day. Serum VD dosage and CAN tests were performed before and after 12 weeks of treatment. There was an improvement in the parameters related to resting heart rate (HR) variability, which were: LF (1.9 ± 0.4 vs 2.2 ± 0.7 sec, p = 0.05), TP (2.5 ± 0.3 vs 2.7 ± 0.5 sec, p <0.05) , RRmax (0.8 ± 0.09 vs 0.9 ± 0.23 sec, p <0.05), RRNN (0.72 ± 0.09 vs 0.76 ± 0.09 sec, p <0.05) and SDNN (0.015 ± 0.005 vs 0.026 ± 0.018 sec; p <0.05). In addition, it was demonstrated that the variation of the RV level correlated with both the final HF (after treatment) and the LF / HF ratio (r = 0.57, p <0.05). Our pilot study is the first to suggest a strong association between high-dose vitamin D supplementation and improved cardiovascular autonomic neuropathy in DM1 patients. This occurred without any variation in HbA1C, blood pressure levels, lipids and insulin doses usedA neuropatia autonômica cardiovascular (NAC), associada ao diabetes mellitus (DM), apesar de ser uma condição subclínica, é um importante fator de morbimortalidade nesses pacientes. No diabetes mellitus tipo 1 (DM1) a NAC é tão alarmante que deve ser rastreada após os cinco primeiros anos de doença, entretanto, poucas medidas terapêuticas são recomendadas nas diretrizes internacionais sobre o assunto. Alguns autores têm avaliado o uso de drogas que possam interferir na história natural da doença e, por conseguinte melhorar a evolução do paciente e reduzir a mortalidade relacionada a esta complicação. A vitamina D aparece como um recurso promissor e de baixo custo. O objetivo de nosso estudo foi avaliar os efeitos da suplementação de altas doses de vitamina D (VD) sobre a NAC em pacientes com DM1. Realizamos um estudo prospectivo, intervencionista, no qual 17 pacientes com diagnóstico de DM1 e NAC foram incluídos. Pacientes com níveis de VD inferiores a 30 ng/mL receberam 10.000 UI/ dia, e quando de 30 a 60 ng/mL, utilizaram 4.000 UI/dia. Dosagem sérica de VD e testes de NAC foram realizados antes e após 12 semanas de tratamento. Houve melhora dos parâmetros relacionados à variabilidade da frequência cardíaca (FC) de repouso, quais sejam: LF (1.9 ± 0.4 vs 2.2 ± 0.7 seg; p=0.05), TP (2.5 ± 0.3 vs 2.7 ± 0.5 seg; p<0.05), RRmax (0.8 ± 0.09 vs 0.9 ± 0.23 seg; p<0.05), RRNN (0.72 ± 0.09 vs 0.76 ± 0.09 seg; p<0.05) e SDNN (0,015 ± 0,005 vs 0,026 ± 0,018 seg; p<0.05). Adicionalmente, foi demonstrado que a variação do nível sérico de VD correlacionou-se tanto com o HF (%) final (pós-tratamento) quanto com a relação LF/HF (r=0,57; p<0,05). Nosso estudo piloto é o primeiro a sugerir uma forte associação entre a suplementação com altas doses de vitamina D e a melhora da neuropatia autonômica cardiovascular em pacientes DM1. Isso ocorreu sem que houvesse variação na HbA1C, níveis pressóricos, lípides e doses de insulina utilizadas.HUJBB - Hospital Universitário João de Barros Barret

Cochlear dysfunction and microvascular complications in patients with type 1 diabetes mellitus

Abstract Sensorineural hearing impairment has been associated with DM, and it is probably linked to the same pathophysiological mechanisms as well-established in microvascular diabetes complications. The study of otoacoustic emissions (OAEs) is useful to identify subclinical cochlear dysfunction. Therefore, the aim of this study was to evaluate the association between abnormal OAEs responses, diabetic kidney disease (DKD) and diabetic cardiac autonomic neuropathy (CAN). We performed a cross-sectional study with 37 type 1 DM patients without auditory symptoms, submitted to the study of Distortion Product Otoacoustic Emissions (DPOAEs) and screened for DKD and CAN. The otoacoustic emissions responses were considered abnormal in 27/37 (73%) patients. A correlation was found between abnormal OAEs responses and presence of DKD (r = 0.36, p < 0.05), and 14/16 (88%) patients with a lower amplitude of OAEs in 8 kHz frequency band presented DKD. Abnormal OAEs responses in the 6 kHz frequency band were correlated with the presence (r = 0.41, p = 0.01) and severity of CAN (r = 0.44, p < 0.001). Additionally, 7/9 (78%) patients with abnormal OAE responses in this frequency also presented abnormal CAN scores. Our results suggest that abnormal otoacoustic emissions responses in high frequency bands are associated with diabetes microvascular complications and could be a risk marker for DKD and CAN, presenting low sensitivity and high specificity. Therefore, assuming that hearing impairment is a pre-clinical stage of hearing loss, performing distortion product otoacoustic emissions in T1DM patients with microvascular complications could be useful to identify those who would be benefit with regular audiologic follow up and tighter diabetes control