Inter-relações entre hipoglicemia e disfunção autonômica cardiovascular no Diabetes Mellitus tipo 1
Data
2015-10-31
Autores
Silva, Ticiana Paes Batista da 
Orientadores
Dib, Sergio Atala
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: a hipoglicemia é um dos principais efeitos colaterais da terapêutica com insulina atual nos pacientes com diabetes mellitus e pode limitar a obtenção do bom controle da glicemia. A percepção à hipoglicemia ocorre através dos sintomas autonômicos e é fundamental para o seu tratamento imediato. A ausência destes sintomas aumenta a chance de evolução para hipoglicemia grave. Outro fator preditivo importante de hipoglicemia grave é a neuropatia autonômica cardiovascular (NAC). Objetivos: o presente estudo tem por objetivo analisar as inter-relações entre grau de hipoglicemia e a percepção clínica à hipoglicemia com disfunção autonômica cardiovascular em pacientes com diabetes mellitus do tipo 1 (DM1). PACIENTES E Métodos: a gravidade da hipoglicemia foi analisada através de um escore de hipoglicemia (EH) e os pacientes foram classificados em dois grupos: hipoglicemia ausente/leve e moderada/grave. O grau de percepção a hipoglicemia foi avaliado através do método de Pedersen-Bjergaard classificando os pacientes em 3 grupos: percepção normal a hipoglicemia, percepção alterada a hipoglicemia e percepção ausente à hipoglicemia. A função autonômica cardiovascular foi determinada pelos Testes de Ewing e pelas medidas da variabilidade da frequência cardíaca (VFC) no domínio do tempo e da frequência. NAC incipiente foi definida pela presença de um teste alterado e NAC clínica pela presença de dois testes alterados dentre os 4 testes de Ewing. Alteração da análise espectral foi definida por alteração de ao menos um teste dentre a banda de baixa frequência (BF) e/ou alta frequência (AF). Resultados: a média de idade dos 99 pacientes incluídos foi de 25,8±10,9 anos, duração média do diabetes foi de 12,8±8 anos e a média da HbA1c foi de 8,4±1,3% (68±10,4 mmol/mol). Os pacientes classificados com hipoglicemia moderada/grave apresentaram maior frequência de retinopatia (p=0,03), nefropatia (p=0,001), complicações macrovasculares (p=0,007) e alteração da análise espectral (p=0,027) quando comparados aos pacientes com hipoglicemia ausente/leve. Após ajuste para características clínicas, alteração da análise espectral (OR: 3,85; IC 95% 1,23?12,02; p=0,020), nefropatia (OR: 4,15; IC 95% 1,27?13,54; p=0,018) e complicações macrovasculares (OR: 12,18; IC 95% 1,14?129,84; p=0,038) permaneceram como preditores independentes de hipoglicemia moderada/grave. A prevalência de percepção alterada a hipoglicemia e ausência de percepção à hipoglicemia foi de 28%. O grau de percepção a hipoglicemia mostrou uma relação inversa com a idade (p=0,001), duração do diabetes (p=0,027), número de episódios de hipoglicemia grave (p=0,005) e prevalência de NAC incipiente (p=0,017). Índices da VFC no domínio da frequência (banda de AF (p=0,027) e poder total do espectro (p=0,037) foram menores no grupo com ausência da percepção à hipoglicemia. Conclusão: disfunção autonômica cardiovascular, avaliada através da alteração da análise espectral, foi preditor independente de hipoglicemia moderada/grave. Ainda, houve uma associação inversa entre o grau de percepção a hipoglicemia e a perda da VFC no domínio da frequência. Nesses pacientes a perda da proteção do sistema nervoso parassimpático representa um componente significativo na disfunção autonômica cardiovascular relacionada a hipoglicemia moderada/grave ou assintomática.
INTRODUCTION: hypoglycemia is the most important side effect of insulin therapy for diabetes and may limit the achievement of good glycemic control. The perception of occurrence of hypoglycemia is dependent of the autonomic symptoms. The absence of these symptoms increases the chance of progression to severe hypoglycemia. Another important predictor of severe hypoglycemia is cardiovascular autonomic neuropathy (CAN). OBJECTIVE: the aim of this study is to evaluate the relationship between the severity of hypoglycemia and hypoglycemia unawareness with cardiovascular autonomic dysfunction in type 1 diabetes mellitus patients. PATIENTS AND METHODS: the degree of hypoglycemia was evaluated by a hypoglycemia score (HYPOsc) and patients were classified into absent/minor or moderate/severe hypoglycemia groups. The patients were assessed for hypoglycemia awareness with the Pedersen-Bjergaard method and were classified into three groups: normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Cardiovascular autonomic function was assessed by the Ewing battery of tests and also by indices of Heart rate variability (HRV) in time and frequency domain. Early CAN was defined by the presence of one abnormal test out of four of the Ewing battery and CAN was defined by the presence of at least two abnormal tests out of four of the Ewing battery. Impaired HRV in the frequency domain (spectral analysis) was defined by an abnormal result of Low Frequency (LF) and/ or High Frequency (HF) of spectral analysis. RESULTS: the mean age of 99 patients included was 25.8±10.9 years. The mean diabetes duration was 12.8±8 years and the mean of HbA1c was 8.4±1.3% (68±10.4 mmol/mol). Patients with moderate/severe hypoglycemia had higher rates of diabetic retinopathy (p=0.03), nephropathy (p=0.001), macrovascular complications (p=0.007) and impaired HRV in the frequency domain (p=0.027) than patients in the absent/minor group. After adjusting for baseline clinical characteristics, impaired spectral analysis (OR: 3.85; 95% IC 1.23–12.02; p=0.020), nephropathy (OR: 4.15, 95% IC 1.27–13.54; p=0.018) and macrovascular complications (OR: 12.18, 95% IC 1.14–129.84; p=0.038) appeared as independent predictors of moderate/severe hypoglycemia. The prevalence of impaired hypoglycemia awareness and hypoglycemia unawareness altogether was 28%. The degree of perception of hypoglycemia showed an inverse correlation with age (p=0.001), diabetes duration (p=0.027), severe hypoglycemia episodes (p=0.005) and the presence of early cardiovascular autonomic dysfunction (p=0.017). HRV measures in frequency domain (high frequency band (p=0.027) and total power (p=0.037)) were significantly lower in the group of unawareness of hypoglycemia. CONCLUSIONS: cardiovascular autonomic dysfunction, assessed by spectral analysis, is an independent predictor of moderate/severe hypoglycemia by the HYPOsc. There is a significant inverse association between the degree of hypoglycemia awareness and loss of HRV in frequency domain. In these patients, the loss of parasympathetic nervous system protection represents a significant component of cardiovascular autonomic dysfunction associated to moderated/severe hypoglycemia or hypoglycemia unawareness.
INTRODUCTION: hypoglycemia is the most important side effect of insulin therapy for diabetes and may limit the achievement of good glycemic control. The perception of occurrence of hypoglycemia is dependent of the autonomic symptoms. The absence of these symptoms increases the chance of progression to severe hypoglycemia. Another important predictor of severe hypoglycemia is cardiovascular autonomic neuropathy (CAN). OBJECTIVE: the aim of this study is to evaluate the relationship between the severity of hypoglycemia and hypoglycemia unawareness with cardiovascular autonomic dysfunction in type 1 diabetes mellitus patients. PATIENTS AND METHODS: the degree of hypoglycemia was evaluated by a hypoglycemia score (HYPOsc) and patients were classified into absent/minor or moderate/severe hypoglycemia groups. The patients were assessed for hypoglycemia awareness with the Pedersen-Bjergaard method and were classified into three groups: normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Cardiovascular autonomic function was assessed by the Ewing battery of tests and also by indices of Heart rate variability (HRV) in time and frequency domain. Early CAN was defined by the presence of one abnormal test out of four of the Ewing battery and CAN was defined by the presence of at least two abnormal tests out of four of the Ewing battery. Impaired HRV in the frequency domain (spectral analysis) was defined by an abnormal result of Low Frequency (LF) and/ or High Frequency (HF) of spectral analysis. RESULTS: the mean age of 99 patients included was 25.8±10.9 years. The mean diabetes duration was 12.8±8 years and the mean of HbA1c was 8.4±1.3% (68±10.4 mmol/mol). Patients with moderate/severe hypoglycemia had higher rates of diabetic retinopathy (p=0.03), nephropathy (p=0.001), macrovascular complications (p=0.007) and impaired HRV in the frequency domain (p=0.027) than patients in the absent/minor group. After adjusting for baseline clinical characteristics, impaired spectral analysis (OR: 3.85; 95% IC 1.23–12.02; p=0.020), nephropathy (OR: 4.15, 95% IC 1.27–13.54; p=0.018) and macrovascular complications (OR: 12.18, 95% IC 1.14–129.84; p=0.038) appeared as independent predictors of moderate/severe hypoglycemia. The prevalence of impaired hypoglycemia awareness and hypoglycemia unawareness altogether was 28%. The degree of perception of hypoglycemia showed an inverse correlation with age (p=0.001), diabetes duration (p=0.027), severe hypoglycemia episodes (p=0.005) and the presence of early cardiovascular autonomic dysfunction (p=0.017). HRV measures in frequency domain (high frequency band (p=0.027) and total power (p=0.037)) were significantly lower in the group of unawareness of hypoglycemia. CONCLUSIONS: cardiovascular autonomic dysfunction, assessed by spectral analysis, is an independent predictor of moderate/severe hypoglycemia by the HYPOsc. There is a significant inverse association between the degree of hypoglycemia awareness and loss of HRV in frequency domain. In these patients, the loss of parasympathetic nervous system protection represents a significant component of cardiovascular autonomic dysfunction associated to moderated/severe hypoglycemia or hypoglycemia unawareness.
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Citação
SILVA, Ticiana Paes Batista da. Inter-relações entre hipoglicemia e disfunção autonômica cardiovascular no Diabetes Mellitus tipo 1. 2015. 85 f. Dissertação (Mestrado em Medicina Translacional) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.