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Doctoral Thesis
DOI
10.11606/T.98.2014.tde-16032015-083602
Document
Author
Full name
Adriana Bertolami Manfredi
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Hirata, Mario Hiroyuki (President)
Araujo, Daniel Branco de
Santos Filho, Raul Dias dos
Spósito, Andrei Carvalho
Title in Portuguese
Aterosclerose subclínica e marcadores de inflamação, de resistência à insulina e genéticos em portadores de hiperglicemia
Keywords in Portuguese
Aterosclerose; Estado pré-diabético; Transtornos do metabolismo de glucose; Ultrassonografia doppler; Tomografia; Teste de esforço.
Abstract in Portuguese
A doença aterosclerótica macrovascular se inicia em fases precoces das alterações do metabolismo glicídico. Este estudo teve por objetivos: 1) avaliar a prevalência de aterosclerose subclínica diagnosticada por métodos não-invasivos em indivíduos com indicação de teste oral de tolerância a glicose; 2) avaliar a distribuição de biomarcadores e de marcadores genéticos nessa população; e 3) determinar os fatores de risco para aterosclerose subclínica em pacientes disglicêmicos. Indivíduos em prevenção primária foram inicialmente submetidos a teste oral de tolerância a glicose e classificados em grupos controle, glicemia de jejum alterada, intolerância à glicose e diabete melito; posteriormente, foram submetidos a pesquisa de aterosclerose subclínica e de biomarcadores, e a avaliação de polimorfismos genéticos e expressão gênica. Foram incluídos 103 pacientes no grupo controle, 80 no grupo glicemia de jejum alterada, 98 no grupo tolerância diminuída à glicose e 59 no grupo diabete melito, com média de idade de 59 + 7,4 anos, sendo 62,4% mulheres. Não foram encontradas diferenças quanto às características clínicas e laboratoriais entre os grupos. Foi observada alta prevalência de aterosclerose subclínica na população (77,1%) e, apesar de não haver diferença entre os grupos, houve tendência a prevalência crescente de acordo com a piora do perfil glicídico. Dentre os biomarcadores, foi encontrada diferença entre os grupos na análise de microalbuminúria, resistina, fator de necrose tumoral alfa e fosfolipase A2 associada a lipoproteína. Não houve diferença com relação aos polimorfismos, mas o grupo glicemia de jejum alterada apresentou maior expressão de mRNA do gene da fosfolipase A2 associada a lipoproteína. Concluímos que indivíduos com indicação de teste oral de tolerância a glicose têm alta prevalência de aterosclerose subclínica, independentemente do perfil glicídico. Após análise multivariada, os fatores que determinaram aterosclerose subclínica foram idade, pressão arterial sistólica, colesterol ligado à lipoproteína de alta densidade, fator de necrose tumoral alfa e uso de estatinas.
Title in English
Subclinical atherosclerosis and inflammation, insulin resistance and genetic markers in hyperglycemic patients
Keywords in English
Atherosclerosis; Pre diabetic state; Disorders of glucose metabolism; Doppler ultrasonography; Tomography; Exercise testing.
Abstract in English
Atherosclerotic macrovascular disease begins in early phases of glucose metabolism alterations. The objectives were: 1) To evaluate the prevalence of subclinical atherosclerosis diagnosed by non-invasive methods in patients with an indication for oral glucose tolerance test. 2) To evaluate the distribution of biomarkers and genetic markers in this population. 3) Determine the risk factors for subclinical atherosclerosis in dysglycemic patients. Individuals in primary prevention underwent oral glucose tolerance test and were classified as controls, impaired fasting glucose, decreased glucose tolerance and diabetics and submitted to subclinical atherosclerosis search, evaluation of biomarkers, genetic polymorphisms and gene expression. A group of 103 patients were included as controls, 80 as impaired fasting glucose, 98 as decreased glucose tolerance and 59 as diabetes with a mean age of 59 ± 7.4 years, 62.4% women. No differences were found between clinical and laboratory characteristics of the groups. High prevalence of subclinical atherosclerosis (77.1%) was observed, although there was no significant difference between groups, a tendency of higher prevalence according to worsening of glucose increasing profile was verified. Among the biomarkers difference between groups were found in the analysis of microalbuminuria, resistin, tumor necrosis factor alfa and phospholipase A2 associated with lipoprotein. There was no difference regardind the polymorphisms, but the impaired fasting glucose group had higher expression of PLA2G7. After multivariate analysis, the factors that determined subclinical atherosclerosis were age, systolic blood pressure, HDL-cholesterol, tumor necrosis factor alfa and statins. We concluded that individuals with indication of oral glucose tolerance test have a high prevalence of subclinical atherosclerosis regardless of glucose profile. The factors that determine the presence of subclinical atherosclerosis were age, systolic blood pressure, HDL-cholesterol, tumor necrosis factor alfa and statins.
 
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Publishing Date
2015-05-12
 
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