DIABETES MELLITUS TYPE II IN THE LIGHT OF METABOLIC SYNDROME Author: Eliška Hrnčířová ¹ Tutor: MUDr. PharmDr. Kamil Rudolf, Ph.D. ¹, š ¹ Department of Clinical and Social Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové š II. intern gastroenterology clinic University Hospital Hradec Králové Background: My thesis deals with diabetes mellitus, a common chronic civilization disease, the essence of its creation, including the issue of the treatment, regime measures and it also mentions the associated health problems connected to the diagnosis. The Aim of the study: The main purpose of this work based on a small sample of patients was to verify their level of information and knowledge of the disease, compliance, participation in home blood glucose measurements and to determine the health complications associated with diabetes and its treatment. Methods: The study was carried out by questionnaire in a paper form. Data were obtained in a pharmacy during a short interview with 209 randomly selected diabetics type II. The questionnaire included two main characteristics of respondents (gender, age) and 6 simple targeted questions. Results: In the survey 59 % female and 41% male took part. The mean age of patients was 66.9 years. Respondents were diagnosed with DM on average 11.1...

Dlabajová D., Antioxidants of natural origin influencing metabolic syndrome, Diploma thesis 2015/2016, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, pp. 61. Large amounts of substances are extracted from plants found all over the world that show antioxidant activity, which prohibits the formation of free radicals. This activity could be beneficial in preventing and curing risk factors of metabolic syndrome. The selection of plants with this effect is shown in my diploma thesis (for example Salvia limbata, Lupinus luteus, Rosmarinus officinalis, Pueraria lobata etc.), which is divided into plant extracts, culinary plants and substances with significant antioxidant activity. Keywords: plants, antioxidants, metabolic syndrome

The aim of this thesis is to contribute to the understanding of iron metabolism, as a factor associated with cardiometabolic risk, by undertaking secondary data analyses. The objectives were to identify gaps in existing knowledge in terms of populations studied and alternative iron markers, and to attempt to fill the gaps with additional analyses and interpretation. Serum ferritin was the most widely available measure of iron status but the role of serum transferrin and soluble transferrin receptor (sTfR) levels was considered where available. I have taken a life-course approach with analyses in childhood and adulthood, and have included both intermediate factors such as the metabolic syndrome (MetS), and disease diagnoses of diabetes and cardiovascular disease as outcomes. Chapter one presents a review of empirical research literature on the relationship between iron metabolism and cardiometabolic risk, concepts surrounding iron markers and the study outcomes. This chapter also describes the gaps in understanding the iron-cardiometabolic risk relationship, which are subsequently explored in chapters two to six. Chapter two explores the link between serum ferritin and transferrin and MetS in cross-sectional and prospective studies of 725 Spanish children and 567 Chilean adolescents. I found associations between both ends of the ferritin distribution and MetS or glucose metabolism markers in different paediatric populations. For instance, whereas in the Spanish children there was a decrease of 0.02 SD units in the change of MetS score over time for every SD unit increase in ferritin, in the Chilean male adolescents being in the highest tertile of ferritin (v. the lowest) was associated with an increase of 0.25 SD units of MetS score. Furthermore, sustained high ferritin levels at various time points and gradual increase of ferritin during childhood were associated with higher MetS score in adolescence. The third chapter describes the association between serum ferritin status and MetS in adults in two cross-sectional studies of Scottish populations (2,047 individuals from Shetland Islands and 8,563 subjects from the Scottish Health Surveys (SHeS) 1995- 1998). I also examined the overall association between ferritin, MetS and each MetS component in adults, by conducting a meta-analysis and investigating potential relevant sources of heterogeneity for the association. Interestingly, ferritin levels were positively associated with MetS in the Scottish populations, but the association was not independent of the effect of covariates, mainly body mass index (BMI) and transaminase levels [Men Odds ratio (OR) 95% confidence interval (CI) 1.43(0.83- 2.46); Postmenopausal women OR (95%CI) 1.09(0.62-1.90); Premenopausal women OR (95%CI) 1.02(0.42-2.46), P > 0.05]. The meta-analysis supported this finding by describing hepatic injury markers and BMI as the major attenuating factors of the ferritin-MetS association. Chapter four investigates the association between sTfR or ferritin, and MetS in 725 Croatian adults in a cross-sectional study. There was no evidence of an association between sTfR and MetS [Men OR (95%CI) 1.35(0.90-2.02); Postmenopausal women OR (95%CI) 0.73(0.47-1.15); Premenopausal women OR (95%CI) 0.87(0.66-1.17), P > 0.05]. In contrast serum ferritin, was positively and independently associated with MetS in men and postmenopausal women (P < 0.05) [Men OR (95%CI) 1.78(1.31- 2.42); Postmenopausal women OR (95%CI) 1.71(1.12-2.62); Premenopausal women OR (95%CI) 1.24(0.85-1.80)]. These contrasting results suggest that different iron markers reflect different physiological processes other than iron metabolism. Chapter five evaluates the longitudinal association between serum ferritin and several cardiometabolic disease outcomes (CMDs) in the nationally representative SHeS 1995 and 1998 (n = 6,497). I found an independent positive longitudinal association between ferritin and cerebrovascular disease (CEVD), which was strengthened by using higher cut-points for increased ferritin [higher v. lowest sextile fully adjusted Hazard ratio(HR) 95%CI 2.08 (1.09-3.94), P=0.024], and a not significant association with coronary heart disease (CHD) after adjustment for covariates. My analyses confirmed the widely established association with type 2 diabetes (T2D) [whole sample fully adjusted HR 95% CI 1.59(1.10-2.34), P=0.006], even with serum ferritin within the normal range. The above set of observations confirm ferritin as biomarker mainly related to the development of T2D and identifies the need to investigate the association between ferritin and CEVD in other populations. Chapter six investigates whether ferritin is associated with risk for cardiovascular complications among people with T2D using cross-sectional study designs in two populations with differing baseline cardiovascular risk (Spanish study SIDIAP n=38,617) and (Edinburgh Type 2 Diabetes Study (ET2DS) n= 821) with additional analysis of follow-up data for ET2DS. Interestingly, ferritin levels were negatively associated with prevalence of cardiovascular disease, mainly CHD, in people with T2D in both studies [ET2DS OR (95%CI): 0.80(0.67-0.96), P=0.020; SIDIAP study: 0.85(0.83-0.88), P < 0.001). Ferritin was also negatively associated with incident cardiovascular disease in ET2DS: HR 95% CI: 0.39(0.16-0.93), P=0.035. Therefore, the association between iron status and CMD risk in people with T2D appears to differ from that in general populations in which a positive association has been more commonly described. In conclusion, serum ferritin is associated with cardiometabolic risk in different ways in a variety of populations. Inconsistent associations for other iron markers suggest that iron biomarkers reflect factors other than iron homeostasis that influence cardiometabolic risk. The association between iron markers and MetS appears to differ between populations. This thesis illustrates the complex relationship between iron metabolism markers, MetS and CMD, and identifies the need for further research on the topic in order to extend knowledge about pathophysiology and the potential for measures of iron status as biomarkers for CMD.

Metabolic syndrome (MetS) is a conglomeration of several risk factors for cardiovascular disease, with obesity currently being one of the common causes of disability and death in the United States.1 Underlying the obesity, however, there is metabolic imbalance that could be exacerbating the issue of metabolic syndrome.2 Approximately 34% of adults over 20 years old matched the criteria for metabolic syndrome.3 The risk factors for cardiovascular disease (CVD) associated with metabolic syndrome can, over time, lead to severe CVDs, such as heart failure (HF).4 Metabolic syndrome can also lead to developing metabolic heart disease over time. Understanding the development of cardiac hypertrophy and fibrosis in diet-induced metabolic heart disease allow development of an early treatment of metabolic heart disease (MHD) and HF. This study looked at one potential mediator and its role in cardiac hypertrophy and fibrosis, follistatin-like 3 (FSTL3). FSTL3 is an extracellular antagonist of members of the TGF-β superfamily. The goal of our study was to determine the effect, if any, a knockout of FSTL3 would have on the development of cardiac hypertrophy and fibrosis after a high-fat, high-sucrose diet for five months. FSTL3 knockout mice were given a high-fat, high-sucrose (HFHS) diet for five months. These mice were then sacrificed and their hearts were analyzed for cardiac myocyte hypertrophy and interstitial fibrosis using histological methods. After five months on the HFHS diet, wild-type (WT) mice had cardiac hypertrophy. In FLRG KO mice the diet-induced cardiac hypertrophy was attenuated. WT HFHS-fed mice developed interstitial fibrosis, and FLRG KO HFHS developed more accentuated interstitial fibrosis than WT HFHS diet fed mice. This study is useful in suggesting that FTSL3 contributes to the pathogenesis of cardiac hypertrophy in MHD. FTSL3 may be a useful biomarker for cardiac hypertrophy in patients with suspected MHD, and may be a viable target for therapeutic interventions aimed at decreasing pathologic myocardial hypertrophy.

A síndrome metabólica (SM) é um conjunto de alterações metabólicas caracterizadas por três de cinco fatores sendo estes; obesidade abdominal, resistência à insulina, hiperglicemia, dislipidemia e hipertensão. As alterações fisiopatológicas da SM são importantes fatores de risco para a doença cardiovascular que tem alta prevalência na maioria das populações. Estudos genéticos têm mostrado que polimorfismos em genes envolvidos em vias do metabolismo glicídico e lipídico estão relacionados com maior predisposição à SM, porém há poucos dados na nossa população. O objetivo deste projeto é estudar a relação entre polimorfismos nos genes LEP, FTO, APOA5, ADRB3, TCF7L2, ENPP1, CYP11B2 e PPARG e a SM. Foram avaliados parâmetros antropométricos, composição corporal, perfil metabólico e de adipocinas, em 167 indivíduos com SM e 262 sem SM, 321 mulheres e 108 homens, e idade entre 30 e 70 anos. Amostras de sangue periférico foram utilizadas para extração de DNA e determinações de perfil lipídico, glicêmico e de adipocinas. Os polimorfismos FTO (rs1421085 T>C, rs1558902 T>A, rs17817449 T>G, rs8050136 C>A, rs9939609 T>A e rs9930506 A>G), LEP rs7799039 G>A, APOA5 rs662799 T>C, ADRB3 rs4994 T>C, TCF7L2 rs7903146 C>T, ENPP1 rs1044498 A>C, CYP11B2 rs1799998 A>G e PPARG rs2972162 C>T foram analisados por PCR em tempo real. As frequências gênicas e alélicas dos polimorfismos estudados foram similares entre os grupos com e sem SM (p>0,05). O haplótipo FTO TTTCAG foi mais frequente no grupo SM (4,2%) do que sem SM (<1,0%, p=0,003), sugerindo que os portadores deste haplótipo tem maior risco de desenvolver síndrome metabólica. Maiores valores de índice de massa corporal (IMC), circunferência abdominal (CA) ou razão cintura-quadril (RCQ) foram observadas nos portadores dos polimorfismos FTO rs1481085 (alelo C), FTO rs1558902 (alelo A), FTO rs17817449 (alelo G), FTO rs8050136 (alelo A), FTO rs9939609 (alelo A), LEP rs7799019 (alelo A), TCF7L2 rs7903146 (alelo C) em comparação com os portadores de genótipos ancestrais (p<0,05), principalmente no grupo SM. Além disso, o polimorfismo FTO rs9930506 (alelo G) foi relacionado com maior teor de gordura corporal (p=0,040), no grupo SM. O SNP CYP11B2 rs1799998 (alelo G) foi relacionado com maior concentração sérica de LDL colesterol e menor concentração de apoAI (p<0,05), grupo SM. Enquanto que a variante ENPP1 rs1044498 (alelo C) foi associada com menor trigliceridemia (p=0,024), no grupo sem SM. Portadores do alelo A do SNP LEP rs7799019 tiveram maior insulinemia e maiores valores de HOMA-&#946; e HOMA-IR que os portadores do genótipo GG (p<0,05), em ambos os grupos, sugerindo a relação desta variante com resistência a insulina. Menores concentrações de leptina foram observadas nos portadores dos SNPs LEP rs7799019 (alelo A) (p=0,031) e ENPP1 rs1044498 (alelo C) (p=0,021) grupo SM; e FTO rs9939609 (alelo A) (p=0,047) no grupo sem SM. A variante FTO rs9930506 (alelo G) foi relacionada com maior adiponectinemia (p<0,05), no grupo SM. Enquanto o SNP ENPP1 rs1044498 (alelo C) foi relacionado com menor concentração sérica de adiponectina nos grupos com (p=0,010) e sem (p=0,006) SM. Em síntese, polimorfismos FTO, LEP e TCF7L2 tem importante papel na adiposidade associada com a síndrome metabólica, em nossa população, e junto com as variantes CYP11B2 ENPP1 contribuem para a variabilidade do perfil metabólico e de adipocinas principalmente em indivíduos com SM. / Metabolic syndrome (MS) is a group of metabolic disorders characterized by three of five factors, which are: abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. The pathophysiological changes of MS are important risk factors for cardiovascular disease that has a high prevalence in most populations. Genetic studies have shown that polymorphisms in genes involved in pathways of glucose and lipid metabolism are associated with increased predisposition to MS, but there are few data on our population. The objective of this project is to study the relationship between polymorphisms in LEP, FTO, APOA5, ADRB3, TCF7L2, ENPP1, PPARG and CYP11B2 and the SM. We evaluated anthropometric parameters, body composition, metabolic profile and adipokines in 167 individuals with MS and 262 without MS, 321 women and 108 men, aged between 30 and 70 years. Peripheral blood samples were used for DNA extraction and determination of lipid profile, glycemic and adipokines. The polymorphisms FTO (rs1421085 T>C rs1558902 T>A rs17817449 T>G rs8050136 C>A rs9939609 T>A and rs9930506 A>G), LEP rs7799039 G>A APOA5 rs662799 T>C ADRB3 rs4994 T>C TCF7L2 rs7903146 C>T, ENPP1 rs1044498 A>C CYP11B2 rs1799998 A>G and PPARG rs2972162C G>T were analyzed by real-time PCR. Genic and allelic frequencies of polymorphisms were similar between the groups with and without MS (p> 0.05). The FTO TTTCAG haplotype was more frequent in the SM group (4.2%) than without MS (<1.0%, p = 0.003), suggesting that carriers of this haplotype have higher risk of developing metabolic syndrome. Higher values of body mass index (BMI), waist circumference (WC) or waist-hip ratio (WHR) were observed in carriers of the FTO rs1481085 polymorphism (C allele), FTO rs1558902 (allele A), FTO rs17817449 (G allele), FTO rs8050136 (allele A), FTO rs9939609 (allele A), LEP rs7799019 (allele A), TCF7L2 rs7903146 (C allele) compared with those with ancestral genotypes (p <0.05), especially in the SM group. In addition, FTO rs9930506 polymorphism (G allele) was associated with higher fat body mass (p = 0.040) in MS group. CYP11B2 SNP rs1799998 (G allele) was associated with increased serum concentration of LDL cholesterol and apoAI lower concentration (p <0.05) SM group. While the ENPP1 variant rs1044498 (C allele) was associated with lower plasma triglycerides (p = 0.024) in the group without MS. Carriers of the A allele of SNP rs7799019 LEP had higher insulin and higher HOMA-&#946; and HOMA-IR than carriers of the GG genotype (p <0.05) in both groups, suggesting the relationship of this variant with insulin resistance. Lower concentrations of leptin were observed in carriers of the LEP SNPs rs7799019 (allele A) (p = 0.031) and ENPP1 rs1044498 (allele C) (p = 0.021) SM group, and FTO rs9939609 (allele A) (p = 0.047) in the group without MS. The variant FTO rs9930506 (G allele) was associated with higher adiponectinemia (p <0.05) in group SM. While the ENPP1 SNPs rs1044498 (C allele) was associated with lower serum concentration of adiponectin in groups with (p = 0.010) and without (p = 0.006) MS. In summary, polymorphisms FTO, TCF7L2 and LEP play an important role in adiposity associated with metabolic syndrome in our population, and along with the CYP11B2 ENPP1 variants contribute to the variability of the metabolic profile of adipokines, especially in individuals with MS.

Type 2 diabetes and metabolic syndrome are the metabolic disorders which constitute a major public health problem in both developed and developing countries. Various studies have suggested the genetic susceptibility to the disorders. The main aim of the thesis was to investigate the putative association of single nucleotide polymorphisms with Type 2 diabetes (T2D), metabolic syndrome (MetS) and the major components of metabolic syndrome. This study used meta‐analysis, polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) and Sanger sequencing methods to analyse the results. The single nucleotide polymorphism rs57829442 of peroxisome proliferator‐activated receptor‐γ coactivator‐1 (PPARGC1A) gene and its relation to risk of type 2 diabetes has been studied in the United Kingdom population. A meta‐analysis of genetic variant rs8192678 (Gly482Ser) of peroxisome proliferator‐activated receptor‐γ coactivator‐1 (PPARGC1A) gene and its association with the components of metabolic syndrome has been studied. An association of the genetic variants rs8192678 (Gly482Ser) of the PPARGC1A gene, rs7903146 of Transcription Factor 7 Like 2 (TCF7L2) gene, rs9939609 of Fat mass and obesity‐associated (FTO) gene and rs1801282 (Pro12Ala) of peroxisome proliferator‐activated receptor gamma (PPARG) gene with the metabolic syndrome and its components has been studied in the Nepalese population. The results showed that variant rs57829442 of PPARGC1A is not associated with T2D in the United Kingdom population. Further investigation with increased sample size is warranted. In the meta‐analysis, the variant rs8192678 (Gly482Ser) of PPARGC1A gene was found to be significantly associated with body mass index (BMI) in Asian populations under dominant genetic model, total cholesterol (TC) in non‐Asian population under recessive genetic model and with fasting plasma glucose (FPG) under a recessive model in overall and non‐Asian populations. No significant association of the variants rs8192678 (Gly482Ser), rs7903146, rs9939609 and rs1801282 (Pro12 Ala) was found associated with MetS under dominant, recessive, co‐dominant and additive models in the Nepalese population. However, the genotypes (AG and AA) of rs8192678 (Gly482Ser) had a statistically significant protective effect on systolic blood pressure. The genotypes with the risk allele of rs9930609 of FTO gene was significantly associated with weight, waist circumference and diastolic blood pressure under dominant genetic model and with BMI under both dominant and recessive genetic models in the Nepalese population. To the best of our knowledge, this is the first study to report the findings in the Nepalese population.

Made available in DSpace on 2014-06-11T19:30:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-11-01Bitstream added on 2014-06-13T19:19:35Z : No. of bitstreams: 1 cambri_lt_dr_rcla.pdf: 6115778 bytes, checksum: d91311fdbb6890a5a464bd78199ad770 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Este estudo teve por objetivo analisar as alterações que a desnutrição fetal provoca na homeostase glicêmica e na capacidade aeróbia, e quais alterações persistem na idade adulta, mesmo após a realimentação, em modelo experimental utilizando ratos. Adicionalmente, visou verificar a susceptibilidade de animais precocemente desnutridos aos efeitos metabólicos da sobrecarga de frutose. Ratas Wistar adultas (90 dias) foram alimentadas durante a prenhez com dieta balanceada (B) - 17% proteína ou hipoproteica (H) - 6% proteína. Imediatamente após o nascimento, as crias do sexo masculino foram distribuídas em grupos de acordo com o regime alimentar até o final do experimento: Balanceada: dieta B durante todo o período experimental; Balanceada/Frutose: dieta B até o nascimento e dieta rica em frutose (F) - 60% frutose até o final do experimento; Hipoproteica/Balanceada: dieta H até o nascimento e dieta B até o final do experimento; Hipoproteica/Frutose: dieta H até o nascimento e dieta F até o final do experimento. Realizou-se duas séries de experimentos, a primeira observando os animais até a idade adulta (90 dias) e a segunda até a idade jovem (60 dias). Os animais foram avaliados quanto a: tolerância à glicose (teste de tolerância à glicose); sensibilidade à insulina (teste de tolerância à insulina) e capacidade aeróbia (teste da máxima fase estável de lactato - MFEL). Foram também analisadas concentrações séricas de glicose, triglicerídeos, colesterol total, LDL-C, HDL-C, ácidos graxos livres, proteínas totais, albumina, concentrações de glicogênio e lipídios totais no fígado; peso e concentração de lipídios totais do tecido adiposo das regiões mesentérica, retroperitonial e subcutânea e metabolismo da glicose pelo músculo sóleo (captação e oxidação da glicose, síntese e concentração de glicogênio)... (Resumo completo, clicar acesso eletrônico abaixo / This study aimed to analyze the alterations that the fetal malnutrition causes in the glycemic homeostasis and in the aerobic capacity, and if this changes persist into adulthood, after the nutritional recovery in an experimental model using rats. Additionally, it aimed to verify the susceptibility of early malnourished animals metabolic effects of fructose overload. Pregnant Wistar rats were fed with a balanced (B) diet or a low-protein (L) diet. After birth and until the end of the experiment, the male offspring were distributed into four groups according to the diet received: B: B diet during the whole experiment; balanced/fructose (BF): B diet until birth and fructose-rich (F) diet afterwards; low protein/balanced (LB): L diet until birth and B diet afterwards; low protein/fructose (LF): L diet until birth and F diet afterwards. Two series of experiments were performed, in the first the animals were observed until adulthood (90 days) and in the second, until young age (60 days). The animals were evaluated for: glucose tolerance (glucose tolerance test), insulin sensitivity (insulin tolerance test) and aerobic capacity (maximal lactate steady state - MLSS). Serum concentration of glucose, triglycerides, total cholesterol, LDL-C, HDL-C, free fatty acids, total proteins and albumin, liver glycogen and liver total lipids, weight and total lipids in adipose tissue in mesenteric, retroperitoneal and subcutaneous regions, and glucose metabolism by soleous muscle (glucose uptake and oxidation, glycogen concentration and synthesis) were analyzed in two conditions: rest and after acute physical exercise in the intensity of MLSS. The results of the first series of experiments show that early high fructose consumption impaired body weight gain and reduced adipose tissue weight of some regions, independently of the nutritional... (Complete abstract click electronic access below)

Orientador: Roberto Carlos Burini / Banca: Luis Carlos Giarola / Banca: Wilson Luvizotto Medina / Resumo: Verificar quais os principais fatores associados com os maiores valores de uricemia, analisando a dieta, composição corporal e marcadores bioquímicos. Foram estudados 1075 indivíduos, de ambos os sexos, com idade entre 21 e 82 anos, participantes de projeto de mudança de estilo de vida. Ácido úrico, glicose, triglicerídios, colesterol total, uréia, creatinina, gama-GT, albumina e cálcio e HDL-c foram quantificados no soro pelo método de química seca. LDL-c foi calculado pela fórmula de Friedewald. Glóbulos brancos, linfócitos e leucócitos foram quantificados por automação. Proteína C-reativa ultra-sensível (PCR-US) pelo método de imunoquimioluminecência. A avaliação antropométrica foi composta pelas medidas de peso e estatura, com posterior cálculo do IMC. Também mediu-se a circunferência abdominal. Massa muscular e % de gordura pela bioimpedância. A ingestão dietética foi realizada através do recordatório de 24 horas, com posterior cálculo das porções da pirâmide e IAS adaptado. Os testes foram realizados utilizando o programa SAS versão 9.1 e o STATISTICA 6.0 e descritos em média + DP. Foi realizado o teste de ANOVA one-way. A nomalidade da amostra foi avaliada pelo teste de Shapiro-Wilk. Correlação de Pearson simples e parcial. Regressão linear (odds ratio), com intervalo de confiança (IC) de 95%, para observar a razão de chance de apresentar o AU acima do útimo quartil (♂AU > 6,5mg/dL e ♀ AU > 5mg/dL). Análise de regressão múltipla "backward stepwise" para determinação dos principais componentes responsáveis pelo aumento do AU.Os resultados foram discutidos com base no nível de significância de p<0,05. IMC e CA correlacionaram-se positivamente e IMM negativamente com as concentrações de AU ajustadas por sexo, idade e antropometria. Dos componentes dietéticos, apenas % de lipídio polinsaturado apresentou correlação... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To evaluate the main dietetic, anthropometric and blood chemistry factors associated with the highest uricemia quartile. One thousand and seventy-five male and female individuals were studied. They were 21 to 82 years old and clinically selected to participated in the lifestyle-change program. Uric acid (UA), glucose, triglycerides (TG), total cholesterol, urea, creatinine, gamma-Gt, albumin, calcium and HDL-c were quantified in serum by the dry chemistry method. LDL-c was calculated by the Friedewald's formula. White cells, lymphocytes and leukocytes were quantified by automation. Ultra-sensitive C-reactive protein (US-CRP) was measured by the immunochemiluminescence method. Anthropometric evaluation consisted of weight and height measurements, which was followed by estimation of the body mass index (BMI). Waist circumference (WC) was also measured. Muscle mass (MM) and fat percentages were estimated by bioimpedance. Dietary intake was evaluated by a 24-hour food recall, and the pyramid servings and the adapted health eating index (HEI) were then calculated. Tests were performed by using the SAS software, version 9.1, and STATISTICA and described by mean + SD. The one-way ANOVA test was also carried out. The sample's normality was evaluated by the Shapiro-Wilk's test, and simple and partial Pearson's correlation was also used. Linear regression (odds ratio) with a confidence interval (CI) of 95% was utilized to observe the odds ratio for presenting UA in the last quartile (♂UA > 6.5mg/dL and ♀UA > 5mg/dL). Backward stepwise multiple regression analysis was used to determine the main components responsible for UA increase. Results were discussed based on the level of significance of p<0.05. BMI and WC were positively correlated and the muscle mass index (MMI) was negatively correlated with UA concentrations adjusted for gender, age and anthropometry. Of the dietary components... (Complete abstract click electronic access below) / Mestre

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T18:24:07Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T18:24:24Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) / Made available in DSpace on 2016-09-22T18:24:24Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) Previous issue date: 2016-05-05 / A prevalência da síndrome metabólica (SM) vem crescendo com o passar dos anos, juntamente com a epidemia da obesidade na população de idosos. O atual processo de transição nutricional contribui para acelerar ainda mais o aparecimento de alterações metabólicas que levam ao diagnóstico da SM, e uma série de fatores ambientais se relacionam com o aparecimento desta doença. Hábitos alimentares inadequados os quais se destacam o consumo excessivo de alimentos refinados, ricos em gordura e uma ingestão reduzida de alimentos integrais, frutas, legumes e verduras, torna a dieta pobre em valor nutricional, possivelmente relacionado à incidência de SM. Além dos fatores mencionados a SM também pode estar relacionada a fatores genéticos, onde os níveis de adiponectina ao contrário das outras substâncias liberadas pelo tecido adiposo agem como fator de proteção para doenças cardiovasculares. Desta forma o presente estudo visou analisar uma possível associação entre o polimorfismo da ADIPOQ 45 T>G, dieta usual e SM em idosos. Foram avaliados marcadores inflamatórios e bioquímicos comparados com grupos de idosos (idade ≥60anos) com e sem SM, além das medidas antropométricas de peso, altura e circunferência da cintura, o polimorfismo ADIPOQ 45 T>G foi determinado através de PCR-RFLP e o consumo alimentar investigado através de questionário de frequência alimentar. Participaram do estudo 111 idosos, onde 53,2% sem SM e 46,8% com SM. Nossos principais resultados mostram que houve relação significativa entre o consumo habitual de leite para o grupo que possuía SM (p<0,05), os níveis de HDL-c, glicose, triglicerídeos e as medidas de peso, altura, circunferência da cintura e pressão arterial diastólica apresentaram-se alteradas no grupo com SM. Houve associação entre o consumo alimentar habitual de carnes brancas e legumes com os haplótipos TG e GG. Conclui-se que não há associação entre o polimorfismo ADIPOQ 45 T>G e SM no grupo de idosos estudados, contudo a relação entre consumo habitual de determinados grupos alimentares e ADIPOQ indicam a necessidade de estudos complementares melhor elucidação desta relação. / The prevalence of metabolic syndrome (MS) has been growing over the years, along with an epidemic obesity in the elderly population. The current nutritional transition contributes accelerate the beginning of metabolic alterations that leads to the diagnosis of MS, and a variety of environmental factors relate to the onset of this disease. Poor eating habits which stand out excessive consumption of refined foods, high in fat and low intake of whole foods, fruits and vegetables, makes the diet low in nutritional value, possibly related to the incidence of MS. In addition to the factors mentioned MS may also be related to genetic factors, which adiponectin levels unlike other substances released by adipose tissue act as a protective factor for cardiovascular disease. Thus, the present study aims to examine a possible association between the polymorphism ADIPOQ 45 T> G, usual diet and MS in the elderly. Inflammatory and biochemical markers compared with older age groups were analyzed (age ≥60 anos) with and without the MS. Also in addition to the anthropometric measurements of weight, height and waist circumference, the ADIPOQ polymorphism 45 T> G was determined by PCR-RFLP and investigated dietary intake through food frequency questionnaire. The study included 111 elderly people, where 53.2% had not the MS and 46.8% had such decease. Our main results show that there was significant relationship between habitual consumption of milk for the group had MS (p <0.05), HDL-C levels, glucose, triglycerides and weight, height, waist circumference and diastolic blood pressure had to be altered in patients with the MS. There was an association between habitual dietary intake of white meat and vegetables with the haplotype TG and GG. We conclude that there is no association between the polymorphism ADIPOQ 45 T> G and MS in the group of elderly studied, however the relationship between habitual consumption of certain food groups and ADIPOQ indicate the need for further studies elucidate this relationship.

abstract: The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has shown that high-fat diet (HFD) consumption can alter the microbial composition of the gut by increasing the abundance of gram-positive bacteria associated with the onset of obesity and type 2 diabetes. Although, the most common form of obesity and metabolic syndrome intervention is exercise and diet, these recommendations may not improve severe cases of obesity. Thus, an important relevance of my project was to investigate whether the intake of an organometallic complex (OMC) would prevent the onset of metabolic and gastrointestinal complications associated with high-fat diet intake. I hypothesized that the consumption of a HFD for 6 weeks would promote the development of metabolic and gastrointestinal disease risk factors. Next, it was hypothesized that OMC treatment would decrease metabolic risk factors by improving insulin sensitivity and decreasing weight gain. Finally, I hypothesized that HFD-intake would increase the abundance of gram-positive bacteria associated with gastrointestinal disease. My preliminary data investigated the effects of a 6-week HFD on the development of hepatic steatosis, intestinal permeability and inflammation in male Sprague Dawley rats. I found that a 6-week HFD increases hepatic triglyceride concentrations, plasma endotoxins and promotes the production of pro-inflammatory cytokines in the cecum wall. I then investigated whether OMC treatment could prevent metabolic risk factors in male Sprague-Dawley rats fed a HFD for 10 weeks and found that OMC can mitigate risk factors such hyperglycemia, liver disease, impaired endothelial function, and inflammation. Lastly, I investigated the effects of a 10-week HFD on the gastrointestinal system and found an increase in liver triglycerides and free glycerol and alterations of the distal gut microbiome. My results support the hypothesis that a HFD can promote metabolic risk factors, alter the gut microbiome and increase systemic inflammation and that OMC treatment may help mitigate some of these effects. Together, these studies are among the first to demonstrate the effects of a soil-derived compound on metabolic complications. Additionally, these conclusions also provide an essential basis for future gastrointestinal and microbiome studies of OMC treatment. / Dissertation/Thesis / Doctoral Dissertation Biology 2019