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Avaliação da influência dos polimorfismos genéticos da dopamina e enzima IDO no consumo alimentar e biomarcadores nutricionais na diabetes mellitus tipo 2
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INTRODUÇÃO: A diabetes mellitus tipo 2 é uma doença metabólica que se caracteriza por um estado crónico de hiperglicemia. Um dos fatores de risco para desenvolvimento de diabetes mellitus tipo 2 é a adoção de uma alimentação desequilibrada. A dopamina é um neurotransmissor associado ao mecanismo de recompensa, que desempenha um papel fulcral no controlo do comportamento alimentar. A enzima IDO participa no metabolismo do triptofano e compete para a produção da serotonina, uma hormona também envolvida no comportamento alimentar. A doença cardiovascular é uma das complicações mais comuns da diabetes e o seu risco é também modificável pelo comportamento alimentar. OBJETIVOS: 1) Avaliar a ingestão alimentar pelo método do registo alimentar das 72 horas; 2) Comparar a ingestão alimentar dos participantes pelos métodos de Questionário de Frequência e Consumo Alimentar e registo alimentar das 72 horas; 3) Determinar os polimorfismos genéticos relacionados com o transportador e o recetor da dopamina (DAT e DRD2); 4) Determinar os polimorfismos genéticos do gene codificador da enzima IDO; 5) Avaliar a influência dos polimorfismos estudados com o consumo alimentar e os níveis plasmáticos de biomarcadores em pessoas com diabetes tipo 2; 6) Relacionar os polimorfismos estudados com a suscetibilidade para o desenvolvimento de angiopatia. MÉTODOS: Foi utilizada uma amostra constituída por 150 adultos portugueses, caucasianos, de ambos os géneros, com idades compreendidas entre os 40 e os 75 anos. Foi aplicado o método do registo alimentar das 72 horas. Os dados recolhidos (alimentos e bebidas) foram convertidos em nutrientes utilizando o software Nutrium®. Os dados alimentares recolhidos no Questionário de Frequência e Consumo Alimentar, bem como as variáveis antropométricas, fisiológicas e bioquímicas foram obtidos por consulta da base de dados criada no âmbito do projeto “Hábitos alimentares, hiperhomocisteinémia e doença cardiovascular na diabetes do tipo 2”. Os métodos de recolha de dados alimentares foram comparados através de uma análise de Bland Altman. Os polimorfismos genéticos foram avaliados por PCR e por real time PCR. A análise estatística dos dados foi realizada utilizando os softwares SPSS®, versão 26.0, considerando valores estatisticamente significativos para p<0,05. RESULTADOS: Os resultados obtidos na comparação dos valores médios de ingestão alimentar obtidos pelo Questionário de Frequência do Consumo Alimentar e pelo registo alimentar das 72 horas permitem encontrar diferenças estatisticamente significativas para a ingestão energética e ingestão de proteína, hidratos de carbono dos quais açúcares, gordura monoinsaturada, gordura trans e sódio. De acordo com a análise de Bland-Altman realizada, é possível concluir que existe concordância entre os dois métodos. No entanto, os valores de erro total e as fraca robustez das correlações analisadas requerem algum cuidado na aplicação dos métodos. Não foram encontradas diferenças estatisticamente significativas na avaliação da ingestão alimentar para cada um dos polimorfismos estudados. Na avaliação dos parâmetros antropométricos, fisiológicos e bioquímicos com os polimorfismos e a presença de angiopatia diabética, foi possível obter resultados significativos para os três polimorfismos. No polimorfismo da DAT foram obtidos valores significativos para o retinol, pressão arterial sistólica, colesterol HDL e triglicéridos no alelo 10 e para o colesterol HDL no alelo 9. Para DRD2 foram observados valores significativos para a homocisteína, cisteína e retinol no alelo A; malondialdeído, homocisteína, cisteína, retinol, pressão arterial sistólica, colesterol HDL e triglicéridos no alelo G; e pressão arterial sistólica e triglicéridos no alelo AG. Para IDO foram obtidos resultados significativos para o retinol, pressão arterial sistólica e triglicéridos no alelo C; homocisteína, cisteína, vitamina B6, retinol e pressão arterial sistólica no alelo T; homocisteína, cisteína, retinol, pressão arterial diastólica e triglicéridos no alelo CT. CONCLUSÃO: Os métodos de avaliação da ingestão alimentar estudados parecem ser concordantes entre si. Não foi possível estabelecer associações diretas entre os polimorfismos estudados e o comportamento alimentar. A avaliação dos parâmetros antropométricos, fisiológicos e bioquímicos com os polimorfismos estudados e a presença de angiopatia diabética permitiu abrir novos caminhos de investigação de acordo com os resultados estatisticamente significativos que foram alcançados.
INTRODUCTION: Type 2 diabetes mellitus is a metabolic disease characterized by a chronic state of hyperglycemia. One of the risk factors for developing type 2 diabetes mellitus is the adoption of an unbalanced diet. Dopamine is a neurotransmitter associated with the reward mechanism, which plays a central role in controlling eating behavior. The enzyme IDO participates in the metabolism of tryptophan and competes to produce serotonin, a hormone also involved in eating behavior. Cardiovascular disease is one of the most common complications of diabetes and its risk is also modifiable by eating behavior. OBJECTIVES: 1) To assess food intake by the 72-hour food record method; 2) To compare the food intake of the participants by the Food Frequency Questionnaire and 72-hour food record methods; 3) To determine the genetic polymorphisms related to dopamine transporter and dopamine receptor (DAT and DRD2); 4) To determine the genetic polymorphisms of the gene encoding the IDO enzyme; 5) To evaluate the influence of the polymorphisms studied with food intake and plasma levels of biomarkers in people with type 2 diabetes; 6) To relate the polymorphisms studied with the susceptibility for the development of angiopathy. METHODS: A sample of 150 Portuguese adults, Caucasian, of both genders, aged between 40 and 75 years was used. The 72-hour food record method was applied. The collected data (food and beverages) were converted into nutrients using the Nutrium® software. The food data collected in the Food Frequency Questionnaire, as well as the anthropometric, physiological and biochemical variables were obtained by consulting the database created within the project "Dietary habits, hyperhomocysteinemia and cardiovascular disease in type 2 diabetes". Dietary data collection methods were compared using a Bland-Altman analysis. Genetic polymorphisms were assessed by PCR and real time PCR. Statistical analysis was performed using SPSS® software, version 26.0, considering statistically significant values for p<0.05. RESULTS: The results obtained from the comparison of the mean values of food intake obtained by the Food Frequency Questionnaire and the 72-hour food record show statistically significant differences for energy intake and intake of protein, carbohydrates of which sugars, monounsaturated fat, trans fat, and sodium. According to the Bland Altman analysis performed, it can be concluded that there is agreement between the two methods. However, the total error values and the poor robustness of the correlations analyzed require some caution in applying the methods. No statistically significant differences were found in the evaluation of food intake for each of the polymorphisms studied. In the evaluation of anthropometric, physiological, and biochemical parameters with the polymorphisms and the presence of angiopathy, it was possible to obtain significant results for the three polymorphisms. In the DAT polymorphism, significant values were obtained for retinol, systolic blood pressure, HDL cholesterol and triglycerides at allele 10 and for HDL cholesterol at allele 9. For DRD2 significant values were observed for homocysteine, cysteine, and retinol on allele A; malondialdehyde, homocysteine, cysteine, retinol, systolic blood pressure, HDL cholesterol, and triglycerides on allele G; and systolic blood pressure and triglycerides on allele AG. For IDO, significant results were obtained for retinol, systolic blood pressure, and triglycerides on the C allele; homocysteine, cysteine, vitamin B6, retinol, and systolic blood pressure on the T allele; homocysteine, cysteine, retinol, diastolic blood pressure, and triglycerides on the CT allele. CONCLUSION: The dietary intake assessment methods studied seem to be concordant with each other. It was not possible to establish direct associations between the polymorphisms studied and eating behavior. The evaluation of anthropometric, physiological, and biochemical parameters with the polymorphisms studied and the presence of diabetic angiopathy allowed opening new avenues of investigation according to the statistically significant results that were achieved.
INTRODUCTION: Type 2 diabetes mellitus is a metabolic disease characterized by a chronic state of hyperglycemia. One of the risk factors for developing type 2 diabetes mellitus is the adoption of an unbalanced diet. Dopamine is a neurotransmitter associated with the reward mechanism, which plays a central role in controlling eating behavior. The enzyme IDO participates in the metabolism of tryptophan and competes to produce serotonin, a hormone also involved in eating behavior. Cardiovascular disease is one of the most common complications of diabetes and its risk is also modifiable by eating behavior. OBJECTIVES: 1) To assess food intake by the 72-hour food record method; 2) To compare the food intake of the participants by the Food Frequency Questionnaire and 72-hour food record methods; 3) To determine the genetic polymorphisms related to dopamine transporter and dopamine receptor (DAT and DRD2); 4) To determine the genetic polymorphisms of the gene encoding the IDO enzyme; 5) To evaluate the influence of the polymorphisms studied with food intake and plasma levels of biomarkers in people with type 2 diabetes; 6) To relate the polymorphisms studied with the susceptibility for the development of angiopathy. METHODS: A sample of 150 Portuguese adults, Caucasian, of both genders, aged between 40 and 75 years was used. The 72-hour food record method was applied. The collected data (food and beverages) were converted into nutrients using the Nutrium® software. The food data collected in the Food Frequency Questionnaire, as well as the anthropometric, physiological and biochemical variables were obtained by consulting the database created within the project "Dietary habits, hyperhomocysteinemia and cardiovascular disease in type 2 diabetes". Dietary data collection methods were compared using a Bland-Altman analysis. Genetic polymorphisms were assessed by PCR and real time PCR. Statistical analysis was performed using SPSS® software, version 26.0, considering statistically significant values for p<0.05. RESULTS: The results obtained from the comparison of the mean values of food intake obtained by the Food Frequency Questionnaire and the 72-hour food record show statistically significant differences for energy intake and intake of protein, carbohydrates of which sugars, monounsaturated fat, trans fat, and sodium. According to the Bland Altman analysis performed, it can be concluded that there is agreement between the two methods. However, the total error values and the poor robustness of the correlations analyzed require some caution in applying the methods. No statistically significant differences were found in the evaluation of food intake for each of the polymorphisms studied. In the evaluation of anthropometric, physiological, and biochemical parameters with the polymorphisms and the presence of angiopathy, it was possible to obtain significant results for the three polymorphisms. In the DAT polymorphism, significant values were obtained for retinol, systolic blood pressure, HDL cholesterol and triglycerides at allele 10 and for HDL cholesterol at allele 9. For DRD2 significant values were observed for homocysteine, cysteine, and retinol on allele A; malondialdehyde, homocysteine, cysteine, retinol, systolic blood pressure, HDL cholesterol, and triglycerides on allele G; and systolic blood pressure and triglycerides on allele AG. For IDO, significant results were obtained for retinol, systolic blood pressure, and triglycerides on the C allele; homocysteine, cysteine, vitamin B6, retinol, and systolic blood pressure on the T allele; homocysteine, cysteine, retinol, diastolic blood pressure, and triglycerides on the CT allele. CONCLUSION: The dietary intake assessment methods studied seem to be concordant with each other. It was not possible to establish direct associations between the polymorphisms studied and eating behavior. The evaluation of anthropometric, physiological, and biochemical parameters with the polymorphisms studied and the presence of diabetic angiopathy allowed opening new avenues of investigation according to the statistically significant results that were achieved.
Descrição
Tese de mestrado, Doenças Metabólicas e do Comportamento Alimentar, Universidade de Lisboa, Faculdade de Medicina, 2022
Palavras-chave
Diabetes mellitus tipo 2 Ingestão alimentar Dopamina Doença cardiovascular Indolamina 2,3-dioxigenase Teses de mestrado - 2022