Avaliação dos níveis de óxido nítrico e estresse oxidativo e sua associação com a enzima conversora de angiotensina em pacientes com diabetes mellitus tipo 2
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Data
2014-03-31
Autores
Mouro, Margaret Gori [UNIFESP]
Orientadores
Higa, Elisa Mieko Suemitsu [UNIFESP]
Tipo
Dissertação de mestrado
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O diabetes mellitus tipo 2 (DM2) é uma das doenças que tem atingido a população mundial ocasionando graves consequências para a saúde deste contingente. O objetivo deste estudo foi avaliar os níveis de óxido nítrico (NO), estresse oxidativo, correlacionando com a atividade da enzima conversora de angiotensina (ECA), em pacientes com DM2. Foram coletadas amostras de sangue e urina isolada em pacientes saudáveis (CTL) e diabéticos tipo 2 (DM2) de ambos os sexos. Nestes pacientes avaliamos: índice de massa corporal (IMC), pressão arterial média (PAM), glicemia de jejum, hemoglobina glicada, creatinina sérica, colesterol, triglicérides, albuminúria, NO, substâncias reativas ao ácido tiobarbitúrico (TBARS) e a atividade da ECA. Nossos resultados mostraram alterações em alguns parâmetros dos pacientes diabéticos. O IMC (Kg/m2) apresentou diferença significante somente no gênero feminino (29,6±5 mulher DM2 vs 25,8±4 mulher CTL; P<0,05). A PAM (mmHg) mostrou diferenças entre: mulher CTL vs homem CTL (88,4±8 vs 100,9±12; P<0,05) e mulher DM2 vs mulher CTL (100,0±14 vs 88,4±8; P<0,05). Já as medidas a seguir foram significantes em ambos os gêneros, mulher DM2 vs mulher CTL e homem DM2 vs homem CTL: glicemia de jejum (mg/dL) (141±64 vs 77±11; P<0,05) e (146±6 vs 81±11; P<0,05); hemoglobina glicada (%) (8,00±2 vs 4,99±5; P<0,05) e (8,00±2 vs 5,09±0,4; P<0,05) e triglicérides (mg/dL) (177,00±90 vs 88,5±27; P<0,05) e (187,00±102 vs 121±88; P<0,05), ou seja, todos elevados quando comparados a seus respectivos controles. Os resultados do NO (µmol/L) apresentaram tendência de aumento nos níveis urinários; entretanto houve um significante aumento nos níveis séricos de ambos os gêneros (67,69 ± 0,5 mulher DM2 vs 37,85 ± 0,3 mulher CTL) e (72,81 ± 0,6 homem DM2 vs 37,05 ± 0,3 homem CTL) P<0,05. A atividade da ECA (nmol/mL) tendeu a aumentar nos pacientes DM2 do gênero masculino; entretanto houve um significante aumento no gênero feminino (73,33 ± 3,24 mulher DM2 vs 46,83 ± 2,61 nulher CTL; P<0,05). As alterações da pressão associadas ao
DM2 poderiam ser responsáveis pelo aumento dos níveis de albuminúria (mg/L), como observado em ambos os gêneros: mulher DM2 vs mulher CTL (82,56±4,08 vs 5,13±0,1; P<0,05) e homem DM2 vs homem CTL (113,15±3,87 vs 5,65±0,3; P<0,05). Notavelmente, os níveis de TBARS no soro não mostraram alterações, contudo os níveis urinários de TBARS (nmol/L) encontravam-se mais elevados no grupo homem DM2 quando comparado ao grupo mulher DM2. Em suma, nosso estudo sugere que o DM2 induz mudanças nos níveis de NO em ambos os gêneros. A atividade da ECA e o TBARS apresentaram diferenças entre os gêneros. Os níveis de NO não estão associados à atividade da ECA. Mais estudos são necessários para esclarecer se as diferenças entre os gêneros na atividade da ECA e no TBARS poderiam estar associadas com a progressão da nefropatia diabetica ou na progressão do DM2 nos pacientes.
The type 2 diabetes mellitus (DM2) is one of the diseases which has hit the world population causing serious health consequences. The aim of this study was to evaluate the levels of nitric oxide (NO), oxidative stress, correlating it with the activity of angiotensin converting enzyme (ACE), in patients with DM2. Blood and urine samples were collected both in healthy (CTL) and type 2 diabetic (DM2) subjects of both genders. The following parameters were evaluated: body mass index (BMI), mean arterial pressure (MAP), fasting plasma glucose, glycated hemoglobin, serum creatinine, cholesterol, triglycerides, albuminuria, NO, substances reacting to thiobarbituric acid (TBARS) and ACE activity. Our results showed changes in some parameters of diabetic patients. BMI (kg/m2) presented a significant difference only in females (29.6±5 DM2 women vs. 25.8±4 CTL women; P<0.05). MAP (mmHg) showed differences both between CTL women and CTL men (88.4±8 vs 100.9±12; P<0.05) and DM2 vs. CTL women (100.0±14 vs 88.4±8; P<0.05). The following measures were significant in both DM2 women vs. CTL women and DM2 men vs CTL men: fasting glucose (mg/dL) (141±64 vs 77±11; P<0.05 and 146±6 vs 81±11; P<0.05); glycated hemoglobin (%) (8.00±2 vs 4.99±5; P<0.05 and 8.00±2 vs 5.09±0.4; P<0.05) and triglycerides (mg/dL) (177.00±90 vs 88.5±27; P<0.05 and 187.00±102 vs 121±88; P<0.05), that is, all high when compared to their respective controls. The results of NO (mol/L) showed a trend of increase in urinary levels, plus a significant increase in serum levels of both genders: (67.69 ± 0.5 DM2 women vs 37.85 ± 0.3 CTL women and 72.81 ± 0.6 DM2 men vs 37.05 ± 0.3 CTL men; P<0.05). ACE activity (nmol/mL) tended to increase in male DM2 patients. However, there was a significant increase in DM2 females as compared to their CTL (73.33 ±3.24 vs 46.83 ± 2.61; P<0.05). Increased levels of albuminuria (mg/L), were observed in both genders: DM2 women vs. CTL women (82.56±4.08 vs 5.13±0.1; P<0.05) and DM2 men vs CTL men (113.15±3.87 vs 5.65±0.3; P<0.05). Notably, the levels of TBARS in serum showed no changes, differently from urinary TBARS levels (nmol/L), which were higher in the DM2 men group compared to the DM2 women group. In conclusion, our study suggests that DM2 induces changes in the levels of NO in both genders. ACE activity and TBARS presented differences between genders. NO levels were not associated with ACE activity. Further studies are necessary to clarify if the gender differences in ACE activity and TBARS could be associated to the progression of diabetic nephropathy or to the outcome of DM2 patientes.
The type 2 diabetes mellitus (DM2) is one of the diseases which has hit the world population causing serious health consequences. The aim of this study was to evaluate the levels of nitric oxide (NO), oxidative stress, correlating it with the activity of angiotensin converting enzyme (ACE), in patients with DM2. Blood and urine samples were collected both in healthy (CTL) and type 2 diabetic (DM2) subjects of both genders. The following parameters were evaluated: body mass index (BMI), mean arterial pressure (MAP), fasting plasma glucose, glycated hemoglobin, serum creatinine, cholesterol, triglycerides, albuminuria, NO, substances reacting to thiobarbituric acid (TBARS) and ACE activity. Our results showed changes in some parameters of diabetic patients. BMI (kg/m2) presented a significant difference only in females (29.6±5 DM2 women vs. 25.8±4 CTL women; P<0.05). MAP (mmHg) showed differences both between CTL women and CTL men (88.4±8 vs 100.9±12; P<0.05) and DM2 vs. CTL women (100.0±14 vs 88.4±8; P<0.05). The following measures were significant in both DM2 women vs. CTL women and DM2 men vs CTL men: fasting glucose (mg/dL) (141±64 vs 77±11; P<0.05 and 146±6 vs 81±11; P<0.05); glycated hemoglobin (%) (8.00±2 vs 4.99±5; P<0.05 and 8.00±2 vs 5.09±0.4; P<0.05) and triglycerides (mg/dL) (177.00±90 vs 88.5±27; P<0.05 and 187.00±102 vs 121±88; P<0.05), that is, all high when compared to their respective controls. The results of NO (mol/L) showed a trend of increase in urinary levels, plus a significant increase in serum levels of both genders: (67.69 ± 0.5 DM2 women vs 37.85 ± 0.3 CTL women and 72.81 ± 0.6 DM2 men vs 37.05 ± 0.3 CTL men; P<0.05). ACE activity (nmol/mL) tended to increase in male DM2 patients. However, there was a significant increase in DM2 females as compared to their CTL (73.33 ±3.24 vs 46.83 ± 2.61; P<0.05). Increased levels of albuminuria (mg/L), were observed in both genders: DM2 women vs. CTL women (82.56±4.08 vs 5.13±0.1; P<0.05) and DM2 men vs CTL men (113.15±3.87 vs 5.65±0.3; P<0.05). Notably, the levels of TBARS in serum showed no changes, differently from urinary TBARS levels (nmol/L), which were higher in the DM2 men group compared to the DM2 women group. In conclusion, our study suggests that DM2 induces changes in the levels of NO in both genders. ACE activity and TBARS presented differences between genders. NO levels were not associated with ACE activity. Further studies are necessary to clarify if the gender differences in ACE activity and TBARS could be associated to the progression of diabetic nephropathy or to the outcome of DM2 patientes.
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Citação
MOURO, Margaret Gori. Avaliação dos níveis de óxido nítrico e estresse oxidativo e sua associação com a enzima conversora de angiotensina em pacientes com diabetes mellitus tipo 2. São Paulo, 2014. 58 f. Dissertação (Mestrado em Medicina Translacional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2014.