Thesis (M.S.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 90-99). Also available on the World Wide Web.

Background: Sedentary behaviour is waking activity in a seated or reclined position that involves little energy expenditure. It is gaining attention as an important cardiometabolic risk factor, independent of physical activity. Studies assessing the relationship between sedentary behaviour and cardiometabolic risk have not accounted for sleep duration as a potential covariate, although there is evidence that sleep duration may be related to both sedentary behaviour and cardiometabolic risk. Objectives: To examine the associations between sleep duration and sedentary behaviour in adults, and determine if sedentary behaviour is related to the metabolic syndrome (MetS) after controlling for sleep duration. Methods: This cross-sectional study used data from the 2003-2006 National Health and Nutrition Examination Survey, a representative sample of Americans. There were 1371 adults over the age of 20 that were studied. Average daily sedentary time and sleep duration were determined via 7-day accelerometry. Screen time (television, computer) was determined via questionnaire. The MetS was determined using standard criteria. Analysis of variance was used to examine relationships among sedentary time and screen time with sleep duration. Multiple logistic regression was used to examine associations between total sedentary time, screen time, and sleep duration with the MetS after controlling for several covariates. Results: Sedentary time and screen time did not vary across sleep duration quartiles (p=0.08 and p=0.87, respectively), and therefore were unrelated to sleep duration. The relative odds of the MetS was significantly higher in participants in the highest quartile of sedentary time than in participants in the lowest quartile (OR=1.60, 95% CI:1.05-2.45). The relative odds of the MetS was higher in participants in the highest screen time tertile than in participants in the lowest tertile (OR =1.67, 95% CI:1.13-2.48). Short sleep duration was not independently related to the MetS, but was borderline related to waist circumference (OR=1.25, 95% CI:0.85-1.84). Conclusion: Highly sedentary individuals and individuals with a high screen time are more likely to have the MetS, independent of sleep duration. Future studies in this area would benefit from using more advanced objective measures of sedentary behaviour and sleep duration and a prospective study design. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2013-10-29 15:40:55.494

Total weekly moderate-to-vigorous (MVPA) accumulated in different patterns has not been well studied: it is not yet known whether sporadic MVPA (periods of <10 consecutive minutes) or whether the weekly frequency of MVPA is associated with health benefits in adults. For this reason, the physical activity guidelines recommend that adults aged 18 to 64 years accumulate at least 150 minutes of MVPA per week in bouts of at least 10 minutes. The overall objective of this thesis was therefore to study the relationships between different patterns of MVPA and the metabolic syndrome (MetS) – a clustering of risk factors that increases the risk of developing cardiovascular disease and type 2 diabetes in adults. Both manuscripts in this thesis used data from the Canadian Health Measures Survey (CHMS), a nationally-representative sample of Canadians. The MetS was determined from direct physical measurements and blood samples, while physical activity levels were assessed by accelerometers (also known as activity monitors). Complex statistical models were used to determine the relationship between patterns of MVPA and the MetS. The first study assessed whether bouted MVPA was associated with lower odds for MetS than an equal volume of sporadic MVPA. Results showed that both bouted and sporadic MVPA were equally related to the MetS; even small bursts of sporadic MVPA <3 minutes in length were meaningful when predicting the MetS. The second study evaluated whether more frequent weekly MVPA was associated with lower odds for the MetS in physically active adults. Among those who were considered physically active, there was no difference in the odds of the MetS between those who were infrequently or frequently active. Together, the results of this thesis suggest that the pattern in which weekly MVPA is accumulated is unimportant, provided that sufficient energy is expended. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2013-07-10 16:01:22.091

Motivation: The detrimental effects of obesity and insulin resistance in Caucasians and African-Americans have been the focus of many recent publications, and the association between PAI-1act and markers of the metabolic syndrome is well established but data on African subjects are still lacking. Objectives: To investigate possible differences between the association of PAI-1act with markers of the metabolic syndrome in Caucasian and African women. Methods We used cross-sectional data from the POWIRS I and II studies, involving 95 African and 114 Caucasian women respectively in the Potchefstroom district of the North West Province, South Africa. Results: Mean plasma PAI-1act was significantly higher in the Caucasian than in the African subjects (p < 0.001). Markers for the metabolic syndrome explained 60% of the variance of PAI-1act in the Caucasian group, but only 2.8% of the variance of PAI-1act in the African group. Waist circumference emerged as the strongest independent predictor of PAI-1act in the Caucasian (34%) as well as the African subjects (11%). Conclusion: This study showed clear differences in PAI-1act between African and Caucasian subjects, along with differences in the association of PAI-1act with markers of the metabolic syndrome. Apparent genetic differences between the two groups (especially the role of the 4G/5G genotype) may have an important influence on PAI-1act The role of PAI-1act in the metabolic syndrome may differ between Caucasians and Africans. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2005.

Background: The metabolic syndrome is associated with an increased risk of diabetes and vascular disease. In order to understand the pathophysiological processes underlying such risk, it is necessary to develop a better understanding of normal fat metabolism and abnormalities associated with the syndrome. The hypothesis tested in this thesis is that specific abnormalities in adipose tissue and muscle fat metabolism characterise the metabolic syndrome. Methods: Fasting biochemical parameters were measured in a cohort of overweight men with and without the metabolic syndrome. Stable-isotope labeling and arterio-venous difference measurements were conducted in 18 men to elucidate pathways of exogenous and endogenous fat metabolism under fasting and postprandial conditions in adipose tissue and skeletal muscle. In addition, a pilot study of the effects of heat and electrical stimulation on adipose tissue metabolism was undertaken. Results: Cohort study - The prevalence of the metabolic syndrome depended on the definition used. Total cholesterol and apoB were greater in those with the metabolic syndrome than in those without. There was no difference in fasting NEFAs. Metabolic investigation - There was significant postprandial uptake of NEFA from the circulating NEFA pool by adipose tissue. Chylomicrons were confirmed as the preferred substrate of LPL. There was preferential uptake of FAs derived from chylomicron hydrolysis. There was release of NEFA across muscle. In the metabolic syndrome, adipose tissue NEFA output is lower during fasting and falls less following a meal than in the healthy obese. Clearance of dietary-derived TG is lower across both adipose tissue and muscle in the metabolic syndrome. Pilot study – Heat increased measures of lipolysis whereas electrical stimulation had no effect. Conclusions: Fat metabolism in individuals with the metabolic syndrome is characterised by metabolic inflexibility but not insulin resistance.

AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype. METHODS Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3. RESULTS Three hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (Delta GT1, p and Delta GT3, p), with TCHOL increasing (+ 5.3, P = 0.005 and + 16.1, P < 0.001), HDL increasing (+ 12.5, P < 0.001 and + 7.9, P = 0.038), LDL increasing (+ 7.4, P = 0.058 and + 12.5, P < 0.001), and TG decreasing (-5.9, P = 0.044 and -9.80 P = 0.067). Among genotypes (Delta GT1 v.Delta GT2 v.Delta GT3, ANOVA), significant mean differences were seen with TCHOL (+ 5.3 v. + 0.1 v. + 16.1, P = 0.017) and HDL (+ 12.3 v. + 2 v. + 7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 (P = 0.028 and P = 0.019). CONCLUSION Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/ GT3. Changes are most pronounced in GT3.

Metabolic syndrome defines a cluster of related comorbidities including obesity, Type 2 diabetes, fatty liver disease, and cardiovascular diseases. Increasingly prevalent in Western countries, metabolic syndrome diseases are a major focus of efforts to understand the complex genetics that underlie disease risk and severity. Immunoglobulin domain-containing receptor 2 (ILDR2) is an ER transmembrane protein first identified as a candidate genetic modifier of diabetes susceptibility in the context of obesity. Obese, leptin-deficient mice with hypomorphic Ildr2 expression had hypoinsulinemic hyperglycemia with reduced beta cell mass, suggesting that ILDR2 plays a role in maintain beta cell mass and function. Further studies proposed a role for ILDR2 in hepatic lipid metabolism as Ildr2 shRNA-mediated knockdown (KD) caused hepatic steatosis in mice. The goal of this thesis work is to clarify the role of ILDR2 in diabetes and hepatic steatosis in an effort to elucidate the specific mechanism of ILDR2. We developed a conditional Ildr2 knockout (KO) allele, enabling tissue-specific ablation in mice. Liver-specific and hepatocyte-specific KO mice did not develop hepatic steatosis. However, liver-specific KO mice treated with adenoviral Ildr2 shRNA accumulated hepatic triglycerides, suggesting off-target effects of the shRNA. Using RNA sequencing and sequence alignment, several gene candidates for shRNA off-targeting effect were identified. Future studies are proposed to elucidate role(s) of these genes in the previously described phenotype of Ildr2 KD mice. I conclude that Ildr2 ablation may contribute to the development of hepatic steatosis, but does not play a major role in hepatic lipid metabolism. We also developed beta cell-specific (RIP2-cre) and pancreas-specific (Pdx-cre) Ildr2 KO mice and characterized them for diabetic phenotypes. Pancreas-specific KO mice displayed impaired glucose tolerance, reduced insulin secretion and decreased calcium signaling in islets. These results confirm a role for ILDR2 in islet cell function. Experiments performed in RIP2-cre beta cell-specific KO mice were confounded by effects of the Cre construct, prohibiting definitive conclusions about the role of ILDR2 in the beta cell. Additionally, because Ildr2 is expressed at low levels in beta cells, we propose that ILDR2 may function in islet macrophages. Overall, this work defines the metabolic functions of ILDR2, clarifying its role in hepatic lipid metabolism, and confirming its role in islet cell function. In addition, I discuss preliminary evidence suggesting that ILDR2 may function in the brain to regulate body weight and metabolism.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Nos Ãltimos anos, a sÃndrome metabÃlica tem despertado profundo interesse e debate na comunidade cientÃfica. A ascensÃo epidemiolÃgica deste distÃrbio ocorre nas mais diversas populaÃÃes e faixas etÃrias, somada à sua capacidade de agregar vÃrios fatores de risco para doenÃas cardiovasculares, como aumento das medidas antropomÃtricas, dislipidemias aterogÃnicas, hipertensÃo arterial sistÃmica, alteraÃÃes do metabolismo dos carboidratos, estado prÃ-inflamatÃrio e prÃ-trombÃtico. Mencionada sÃndrome està associada ao maior risco de desenvolver diabetes mellitus tipo 2, doenÃa coronariana precoce e altas taxas de morbimortalidade para complicaÃÃes cardiovasculares. Teve-se como objetivo geral analisar a circunferÃncia do pescoÃo como possÃvel marcador para a sÃndrome metabÃlica em estudantes de uma universidade pÃblica de Fortaleza-CE. Trata-se de um estudo exploratÃrio, quantitativo, transversal e observacional realizado de marÃo de 2010 a junho de 2011 na Universidade Federal do CearÃ, com 702 universitÃrios das seis grandes Ãreas do conhecimento. Participaram do estudo 440 mulheres e 262 homens com idade entre 16 e 58 anos. Percebeu-se associaÃÃo entre a CP e os dados sociodemogrÃficos; 43,9 % dos homens e 7,1% das mulheres apresentaram CP elevada, sendo estatisticamente significante, p < 0,0001 em ambos os sexos. SituaÃÃo semelhante se deu com a idade (p< 0,001), com a situaÃÃo laboral (p<0,031) e com o semestre (p < 0,012). Em relaÃÃo à prÃtica de atividade fÃsica, 22,4% dos sujeitos que praticam algum tipo de atividade fÃsica regular tiveram a CP elevada (p < 0,503). O IMC tambÃm se mostrou estatisticamente significante com p<0,0001. A CP denotou correlaÃÃo positiva com todos os componentes da sÃndrome metabÃlica segundo os critÃrios do NCEP/ATP III. Conforme se concluiu, a CP à um marcador preditor para sÃndrome metabÃlica numa populaÃÃo de universitÃrios. Contudo, ressalta-se a importÃncia de outros estudos sobre essa temÃtica. / In recent years, the metabolic syndrome has aroused profound interest and debate in the scientific community. The epidemiological ascent of this disorder occurs in a wide range of populations and age groups, in addition to its capacity to aggregate various risk factors for cardiovascular illnesses, such as increased anthropometric measures, atherogenic dyslipidemias, systemic arterial hypertension, alterations in carbohydrate metabolism, pro-inflammatory and pro-thrombotic status. This syndrome is associated with a greater risk of developing type 2 diabetes mellitus, early coronary disease and high morbidity and mortality levels for cardiovascular complications. The general aim was analyze neck circumference as a possible marker for the metabolic syndrome in students at a public university in Fortaleza-CE. An exploratory, quantitative, cross-sectional and observational study was developed between March 2010 and June 2011 at University Federal of CearÃ, involving 702 college students from the six large knowledge areas. Study participants were 440 women and 262 men between 16 and 58 years of age. An association was perceived between neck circumference (NC) and sociodemographic data: 43.9% of men and 7.1% of women showed altered NC, with statistical significance at p < 0.0001. A similar situation occurred for age (p< 0.001), occupational situation (p<0.031) and the semester (p < 0.012). Concerning physical exercise, 22.4% of the subjects who exercise regularly displayed altered NC (p < 0.503). The BMI also showed statistical significance with p<0.0001. NC indicated a positive correlation with all metabolic syndrome components according to NCEP/ATP III criteria. In conclusion, NC is a predictive marker of the metabolic syndrome in a population of college students. The importance of further research on this theme is highlighted though.

[Truncated abstract] Dyslipidaemia in obesity and the metabolic syndrome is typically characterized by elevated plasma concentrations of apolipoprotein (apo) B and chylomicron remnants, and low apoA-I levels. This may account for the increased risk of cardiovascularrelated diseases. Although the precise mechanisms whereby visceral obesity confers the onset of dyslipidaemia have not been fully established, it may relate chiefly to insulin resistance. Insulin resistance leads to increased hepatic secretion of very low density lipoprotein (VLDL) apoB, as well as impaired catabolism of VLDL, intermediate density lipoprotein (IDL), low-density lipoprotein (LDL) and chylomicron remnants, and high density lipoprotein (HDL) apoA-I. This thesis tests the unifying hypothesis that lipoprotein metabolism, in particular apoB, chylomicron remnants and apoA-I, is abnormal in the metabolic syndrome, and that medical intervention can correct for these abnormalities. The primary objectives were to examine firstly, the kinetics of apoB and apoA-I by stable isotope technology and secondly, chylomicron remnant kinetics by using an indirect assessment of a new breath test. Six observational statements and related hypotheses were constructed and derived from the unifying hypothesis that examine the kinetics of lipoprotein metabolism, adipose tissue mass compartments and liver fat accumulation, as well as the impact of plasma adipocytokines in subjects with visceral adiposity and features of the metabolic syndrome. The first four observational statements related to cross-sectional studies of lipoprotein kinetics, adipose tissue mass distribution and liver fat accumulation as well as plasma adipocytokines in both obese and non-obese men. The latter two observational statements related to the effect of statin therapy and dietary weight loss on the improvement of lipoprotein kinetics in obesity. The findings from these studies collectively support the unifying hypothesis. The kinetics of apoB in VLDL, IDL and LDL, and apoA-I in HDL were assessed by gas-chromatography mass spectrometry following either a primed-constant infusion of 13C-leucine or an intravenous bolus injection of d3-leucine. ... This is the first study to examine the effects of dietary weight loss on LDL and HDL metabolism and the relationships with adipocytokines in men with the metabolic syndrome. The data support the unifying hypothesis that medical intervention with dietary weight loss could correct the kinetic abnormalities in VLDL, LDL and HDL. The aforementioned studies showed that plasma lipid and lipoprotein abnormalities in visceral obesity are chiefly regulated by the combination of hepatic over-secretion of VLDL particles, and catabolic defects in apoB and chylomicron remnants as well as apoA-I-containing lipoprotein particles. These kinetic defects may also relate to low and high plasma adiponectin and RBP-4 levels, respectively. The data arising from the thesis are consistent with the unifying hypothesis and support the role of dietary intervention and pharmacotherapy as a recommended treatment in correcting the abnormalities in lipoprotein metabolism within the metabolic syndrome.

Introduction: Subjects with insulin resistance (IR) and diabetes are at increased risk of cardiovascular disease (CVD) than those without diabetes, however the mechanistic basis remains elusive. Despite LDL-cholesterol lowering by statin therapy, two-thirds of all CVD events remain, constituting a significant 'residual risk' for CVD. This ‘residual risk’ has been found to be greater for patients with diabetes than those without diabetes. This suggests the role for alternative sources of lipoprotein-derived cholesterol in CVD during diabetes. Both type-1 diabetic as well as IR subjects have been found to have increased plasma concentrations of fasting intestinal derived apoB48 containing remnants (CM-r). However it is not known if the diabetic metabolic milieu indeed increases the susceptibility of the arteries to CM-r and if these indeed bind to arterial proteoglycans (PGs). Objectives: To determine arterial retention of CM-r in type-1 diabetes and IR using ex vivo perfusion methodology in a streptozotocin rat model of type 1 diabetes and JCR-LA-cp rat model of IR. To determine the direct binding affinity and capacity of CM-r to biglycan using an in vitro approach. Methods and Results: We observed increased arterial CM-R retention in type 1 diabetic vessels as well as in IR vessels when compared to control vessels. The retained CM-r colocalized with arterial biglycan in type 1 diabetic vessels and a direct correlation was observed between the CM-r and the presence of glycated proteins in type I diabetic arteries. The increased arterial CM-r retention in the IR rats was associated with increased arterial biglycan protein content. We have conclusively demonstrated for the first time that CM-r indeed bind to human biglycan. Conclusion: Tight glycemic control in patients with type 1 diabetes can alleviate CVD by reducing hyperglycemia and subsequent retention of CM-r. A significant increase in biglycan protein core content during IR is suggestive of early vascular remodeling and may help to explain how CM-r accumulate more readily during diabetes induced CVD. Based on the results from this study, individuals with IR may be at increased risk for atherogenesis due to increased atherogenicity of the post-prandial CM-r when compared to normal population. / Nutrition and Metabolism