The prevalence of insulin resistance and type 2 diabetes mellitus (T2DM) in obese children and adolescents is growing at an alarming rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds vary in their metabolic response to excessive adiposity. Differences in lipid partitioning in the abdominal fat compartments have been observed among different ethnic groups. The aim of this study was to evaluate whether there are ethnic differences in intramyocellular lipid (IMCL) levels that are related to differences in insulin sensitivity. Eighty-two obese children and adolescents underwent 1) 1H nuclear magnetic resonance (NMR) spectroscopy to non-invasively quantify IMCL levels in their soleus muscle, 2) an oral glucose tolerance test and (in a subset of subjects) a euglycemic-hyperinsulinemic clamp to assess insulin sensitivity, 3) a dual-energy X-ray absorptiometry (DEXA) scan to measure total percent body fat, and 4) magnetic resonance imaging to measure abdominal fat distribution. IMCL levels in Hispanic children and adolescents (1.50 ± 0.64%) were significantly greater than in their Caucasian (1.19 ± 0.40%) and African-American (1.09 ± 0.49%) peers. Visceral fat was significantly lower in African Americans (42.7 ± 18.8cm2) and were similar in Caucasians (70.9 ± 27.5cm2) and Hispanics (77.3 ± 41.9cm2). The three groups were not different with respect to insulin sensitivity. For the entire cohort, IMCL levels were inversely related to insulin sensitivity. There was a significant correlation between visceral fat and insulin resistance in Hispanics and Caucasians but not in African Americans. In conclusion, these data suggest that there are significant ethnic differences in lipid partitioning in both the muscle and abdominal compartment. These findings may explain ethnic differences in insulin sensitivity and further the understanding of the pathogenesis of insulin resistance and T2DM.

10,291 participants, aged 20 to 85 years of age, available from the 1999 through 2002 NHANES databases participated in this study. Only 8,485 (82%) of these participants were included in the data analysis. Participants who were pregnant (n = 603), not examined at a mobile examination center (n = 820), or had missing values for height (n = 164) and/or weight (n = 125) were eliminated. Individuals were classified into four groups (underweight, normal, overweight and obese) based on body mass index (BMI). Variables measured in the study included body mass index, physical fitness, dietary folic acid, c-reactive protein, homocysteine, folate, serum total cholesterol, serum triglycerides, HDL-C, and glucose. All data was collected at Mobile Examination Centers (MEC). The results of the present study showed that being overweight and obese were associated with a poor serum lipid profile, higher serum glucose levels, lower participation in physical activity and a lower physical fitness level. Being overweight and obese was also associated with higher serum levels of inflammatory markers for cardiovascular disease (CVD). Overweight and obese individuals are also being diagnosed with coronary heart disease (CHD) at a younger age.

Made available in DSpace on 2017-07-21T19:59:57Z (GMT). No. of bitstreams: 1 Lucia Hoffmann.pdf: 1860358 bytes, checksum: d1a047a5d9cc402bd848a17fc42409b4 (MD5) Previous issue date: 2012-12-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Apolipoprotein B (apoB) is the principal protein from low density lipoprotein (LDL) involved in cholesterol metabolism and transport. Single nucleotide polymorphisms (SNPs) in the human apoB gene have been associated with cardiovascular disease risk, such as Coronary Artery Disease (CAD), dyslipidemia and atherosclerosis. These multifactorial diseases are generated by interaction between environmental and genetic factors. Previous works investigated the genetic causative components of these diseases and focused mainly on polymorphisms that occur in genes encoding structural proteins and enzymes related to lipid profile. The present study aimed to investigate the MspI polymorphism in the apoB gene association with cardiovascular risk factors in a case-control patients group from the Campos Gerais region (Paraná, Brazil) population, moreover to determine this polymorphism allele and genotype frequencies, and also to associate the obtained genetic data with cardiac risk related variables by using correlation analysis. We evaluated 66 patients, from which 55 patients formed the cardiovascular risk group, and 11 others composed the group without risk – control. The patients mean age was 60 ± 10.0 years in the group with risk and 53 ± 14.0 years in the control group. The MspI polymorphism (exon 26) on apoB gene was characterized by PCR-RFLP and, after restriction, DNA fragments were identified by electrophoresis using agarose gel. The normal allele was named M1 and the mutated allele was called M2. The obtained values for MspI polymorphism genotypic frequencies were 0.82, 0.09, 0.09 for the control group, and 0.76, 0.24, 0.00 for the CAD risk group, respectively for genotypes M1M1, M1M2, M2M2. It was showed that the M1M1 homozygous was dominant in the genotype distribution for both groups. There was no significant difference between the allele and genotype frequencies for MspI polymorphism in the apoB gene (2 = 5.90, P > 0.05; Contingency Test) when comparing the two groups. Therefore, the distribution of the studied polymorphism in the Campos Gerais region population presented to be in Hardy-Weinberg equilibrium both for the control group and for the CAD risk patients group, keeping stable the polymorphism, what was already previously reported for Chinese and Korean populations. The Pearson correlation analysis performed between the risk variables (age, diabetes mellitus, high LDL, high triglycerides, low HDL, hypothyroidism, weight, body mass index) showed correlation between the most of the variables for M1M1 and M1M2 genotypes. But for the total population (n = 66), the association of the apoB gene polymorphism was not correlated with cardiac risk variables. In the end, this research presented data for understanding the association of apoB gene polymorphism with lipid metabolism disorder in the development of risk factors for cardiovascular disease in the population of Campos Gerais (PR). / A apolipoproteína B (apoB) é a principal proteína da lipoproteína de baixa densidade (LDL) que está envolvida no transporte e metabolismo do colesterol. Polimorfismos de único nucleotídeo (SNPs) no gene da apoB humana têm sido associados ao risco para doenças cardiovasculares, como a Doença Arterial Coronariana (DAC), as dislipidemias e a aterosclerose. Estas doenças são caracterizadas como multifatoriais, causadas pela interação entre fatores ambientais e genéticos. Estudos de investigação dos componentes genéticos causadores destas doenças têm focado principalmente em polimorfismos nos genes que codificam proteínas estruturais e enzimas relacionadas ao perfil lipídico. Este trabalho teve como objetivo investigar a associação do polimorfismo MspI no gene da apoB com os fatores de risco cardiovascular em um grupo de pacientes caso-controle na população da Região dos Campos Gerais (Paraná, Brasil), além de determinar as frequências alélicas e genotípicas deste polimorfismo, e associar os dados genéticos obtidos com as variáveis relacionadas aos riscos cardíacos através da análise de correlação. Foram avaliados 66 pacientes, dos quais 55 compuseram o grupo com risco cardiovascular, e os 11 demais formaram o grupo sem risco – controle. A idade média dos pacientes foi de 60 ± 10,0 anos no grupo com risco e 53 ± 14,0 anos no grupo controle. O polimorfismo MspI (exon 26) no gene da apoB foi caracterizado por PCR-RFLP, sendo os fragmentos de DNA, após a restrição, identificados por eletroforese em gel de agarose. O alelo normal foi denominado M1 e o alelo mutado M2. As frequências genotípicas encontradas para o polimorfismo MspI foram 0,82, 0,09 e 0,09 para o grupo controle; e 0,76, 0,24 e 0,00 para o grupo de pacientes com risco, respectivamente para os genótipos M1M1, M1M2 e M2M2. O homozigoto M1M1 foi predominante na distribuição genotípica para ambos os grupos. Não houve diferença significativa entre as frequências genotípicas e alélicas do polimorfismo MspI no gene da apoB (2 = 5,90; P > 0,05; Teste de Contingência), quando comparados os 2 grupos em estudo. Assim, a distribuição do polimorfismo estudado na população da região dos Campos Gerais (PR) se mostrou no equilíbrio de Hardy-Weinberg, tanto no grupo controle quanto no grupo de pacientes com risco cardíaco, mantendo o polimorfismo estável, sendo estes resultados também relatados para as populações chinesa e coreana. Na análise de correlação de Pearson entre as variáveis de risco (idade, diabetes mellitus, LDL alto, triglicerídios alto, HDL baixo, hipotireoidismo, peso, índice de massa corporal), observou-se que a maioria das variáveis analisadas se correlacionaram para os genótipos M1M1 e M1M2. Já para a população total estudada (n = 66), a associação do polimorfismo gênico da apoB não apresentou correlação com as variáveis de risco cardíaco. Enfim, esta pesquisa apresentou dados para o entendimento da associação do polimorfismo do gene da apoB com o distúrbio de metabolismo lipídico no desenvolvimento de fatores de risco para doenças cardiovasculares na população dos Campos Gerais (PR).