Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/15628
Título: Hábitos alimentares, hiperhomocisteinémia e doença cardiovascular na diabetes do tipo 2
Autor: Valente, Ana Margarida Saraiva, 1979-
Orientador: Costa, Helena Soares
Bicho, Manuel Pires, 1950-
Palavras-chave: Homocisteína
Doenças cardiovasculares
Diabetes Mellitus Tipo 2
Teses de doutoramento - 2014
Data de Defesa: 2014
Resumo: Diabetes mellitus is a chronic disease with high social, human and financial costs. Nowadays it is considered one of the greatest public health problems and only in Portugal there are over a million of diabetics. Type 2 diabetes and changes of homocysteine metabolism are both associated with the cardiovascular disease. Several epidemiological studies indicate that moderate hyperhomocysteinemia increases oxidative stress by promoting the formation of atheroma plaque. This mechanism can be reduced by a rich diet in antioxidant micronutrients. Several studies have shown that increasing the intake of good food sources of vitamins A, C, E and carotenoids, reduces atherosclerosis progression and prevents the development of cardiovascular disease. The quantification and assessment of plasma homocysteine levels in type 2 diabetics is not a common practice in Portugal. National studies on this topic, do not characterize the overall risk of development and/or progression of vascular complications by increasing plasma levels of homocysteine and cysteine, and also by serum or plasma changes of oxidative stress markers and antioxidant vitamins in type 2 diabetes. AIMS: (1) To assess the nutritional status of a sample of the Portuguese population and to relate obesity with serum or plasma levels of biochemical compounds under study, (2) To characterize the dietary habits of the study population and to correlate them with its plasma levels of homocysteine and cysteine; (3) To relate the presence of type 2 diabetic angiopathy with hyperhomocysteinaemia, hypercysteinaemia, oxidative stress and decreased levels of plasma or serum antioxidants (vitamins A, C and E and carotenoids) and cofactors of homocysteine metabolism (vitamins B12, B6 and folate) and, (4) to evaluate the contribution of genetic variation of Hp and the C667T polymorphism of methylenetetrahydrofolate reductase with plasma levels of homocysteine and cysteine in diabetic angiopathy. METHODS: A population-based case-control study in 300 Portuguese adults of both genders, aged 40 to 75 years was performed. The study population was divided into three groups: group I - 75 type 2 diabetics with angiopathy, group II - 75 type 2 diabetics without angiopathy, group III - 150 controls. Plasma levels of homocysteine, cysteine, malondialdehyde, vitamins B6, C, A and E and carotenoids were measured by high-performance liquid chromatographic methods. The assay to measure vitamin B12 and folate in serum was carried out by an electrochemiluminescence method. The polymorphisms of haptoglobin and the C677T of methylenetetrahydrofolate reductase were identified in both of the studied diabetic groups. Anthropometric data were obtained by standard techniques and the prevalence of obesity was assessed by three different methodologies. The body composition of the participants was assessed by applying the tetrapolar bioimpedance method. The percentage of body fat was also calculated by applying 9 anthropometric equations. The agreement between anthropometric equations and bioimpedance method was evaluated by performing the Bland-Altman analysis and applying the Lohman criterion. A standard questionnaire was also performed to obtain general data, clinical and physical activity. The eating habits of the participants in the past 12 months were assessed by applying a food frequency questionnaire validated for the Portuguese adult population. The statistical analysis was performed using SPSS® version 20.0 and MedCalc® version 12.3.0. RESULTS: According to the evaluation criteria of body mass index, the prevalence of obesity was higher in both diabetic groups (group I: 57.3% vs. Group II: 45.4%) compared with the group of nondiabetic (16.8%). When the abdominal waist methodology was applied, the prevalence of obesity was very high in all groups (>50%) and significantly higher in groups I and II (70.7%) compared to group III (51.0 %). Obesity prevalence assessed by the percentage of body fat (bioimpedance method) was also very high in the whole population (>75%), but not statistically different between groups. The Deurenberg equation (1998) was the most consistent with the bioimpedance method. The method of body mass index underestimated the prevalence of obesity in the studied population. The body composition results showed that the average of body fat percentage, lean body mass and total body water were similar between groups. The prevalence of dehydration in the study population was very high (>55%). The average daily intake of energy and total fat was higher in group I than in group III. The average daily intake of carbohydrates was similar in all groups and that of protein was higher in diabetic patients compared to controls. The average daily intake of water for all groups was lower than the values recommended by the European Food Safety Authority. The prevalence of inadequate intake of total dietary fiber was greater than 50% in all groups. Inadequate intake of eicosapentaenoic acid, docosahexaenoic acid, omega-6 and omega-3 fatty acids was very high for the whole study population (>70%). The prevalence of total dietary sodium intake above the amount recommended by the World Health Organization was very high in all groups (>80%). The prevalence of inadequate intake of eight micronutrients was above 55% in all groups and the non-diabetic group showed the highest prevalence of inadequacy for ten of the 24 micronutrients assessed. The pattern of intake of vitamins and minerals in the two groups of type 2 diabetes was very similar. The presence of type 2 diabetes increases the risk of hyperhomocysteinemia, high levels of malondialdehyde and that of hypovitaminosis C. Angiopathy increases the occurrence probability of hyperhomocysteinemia and oxidative stress but not hypovitaminosis C. The prevalence of low plasma levels of ascorbic acid and pyridoxal-5-phosphate in the studied population was relevant (>30%). Direct associations of homocysteine, cysteine and malondialdehyde with body mass index, waist circumference and body fat were observed. In turn, there was an inverse relationship of ascorbic acid, lutein and β-cryptoxanthin with the same anthropometric parameters. In the relation between food intake and serum concentrations of aminothiols, a direct association of homocysteine and cysteine with the intake of methionine and lysine was observed. The distribution of haptoglobin and the C667T methylenetetrahydrofolate reductase polymorphisms was similar in both groups of the studied diabetics. The presence of the Hp 2-1 genotype was associated with a predisposition to the occurrence of hyperhomocysteinemia and hypercysteinemia in type 2 diabetics with angiopathy. The diabetic patients of group I who carry the genotypes Hp 2-1 or Hp 2-2 had a probability risk four times higher to have an elevated plasma homocysteine level than diabetics without angiopathy. The presence of 667TT and C667T genotypes in diabetic patients of group I increases in five times the occurrence probability to have hyperhomocysteinemia in relation to diabetic patients of group II. The combined effect of the polymorphism of haptoglobin and the C667T of methylenetetrahydrofolate reductase polymorphism increased the occurrence probability of hypercysteinemia in diabetics with angiopathy. CONCLUSION: The prevalence of obesity was greater than 70% in the whole population when evaluated by the criteria of body fat percentage or abdominal waist. The Deurenberg equation (1998) proved to be the most suitable for measuring the body fat percentage in Caucasian adults with or without type 2 diabetes. Both diabetic groups showed a similar pattern of nutrient intake and a prevalence of inadequate intake lower than the obtained in the control group for 10 of the 24 assessed micronutrients. Diabetes mellitus type 2 is a predisposing factor for hyperhomocysteinemia, hypercysteinemia, oxidative stress and hypovitaminosis C. Obesity in type 2 diabetes is directly associated with homocysteine, cysteine and malondialdehyde and inversely with ascorbic acid, lutein and β-cryptoxanthin. The presence of genotypes Hp 2-1 and Hp 2-2 in type 2 diabetics with angiopathy predisposes to hyperhomocysteinemia and hypercysteinemia. Angiopathy in type 2 diabetic patients with the CT or TT genotypes of the C667T polymorphism of methylenetetrahydrofolate reductase promotes hyperhomocysteinemia. The interaction between the genotypes of C667T and Hp 2-1 methylenetetrahydrofolate reductase enhances the presence of hypercysteinaemia.
Descrição: Tese de doutoramento, Ciências e Tecnologias da Saúde (Nutrição), Universidade de Lisboa, Faculdade de Medicina, 2013
URI: http://hdl.handle.net/10451/15628
Designação: Doutoramento em Ciências e Tecnologias da Saúde
Aparece nas colecções:FM - Teses de Doutoramento

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