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.

[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

Disparities in medication adherence (MA) associated with African American (AA) adults may be related to a dynamic interplay between personal factors, behavioral capability, and environmental factors. The purpose of the study was to examine this relationship in AA adults with metabolic syndrome (MetS). A cross-sectional, correlational analysis was conducted from baseline data from a larger intervention study. Constructs from the Social Cognitive Theory were used to predict MA. The sample of 91 AA adults with MetS was primarily middle-aged (age range 45-70 years old; M 53, SD 6.3), female (79%), relatively well-educated, and married. Despite being on antihypertensive medications, 53% of the participants presented with uncontrolled high blood pressure (≥130/90 mmHg). Although the vast majority (95%) of the sample displayed adequate health literacy (HL), 30% of the sample was non-adherent to their medication regimen. A positive significant relationship was found between age and MA [χ2 (1, n = 90) = 6.71, p = .01)]. Stress [χ2 (1, n = 90) = 6.28, p = .012)] and social support (SS) [χ2 (1, n = 90) = 4.10, p = .04)] were the only significant relationships among environmental factors, barriers and hypertension MA. Highly stressed AA adults were significantly more likely to be non-adherent or had a 15% reduction in the odds of hypertension MA. Similarly, adults with a low income were 5.8 times more likely to be non-adherent (OR 5.828, 95% CI, 1.014-33.493, p= .0482), while those with low SS had a 9% reduction in the odds of MA; SS trended toward significance (OR.914. 95% CI .823-1.016, p =.09). With increasing age, AA adults were more likely to be non-adherent (OR 1.12, 95% CI 1.028-1.220, p =.0096). Most of the participants reported a high degree of autonomy, satisfaction with their health care climate, and the availability of SS. Although increasing age, adequate SS, high stress, and adequate HL appeared to influence MA in AA adults with MetS, the research questions were only partially answered. Further investigation of the relationships and potential mediating pathways between personal characteristics, environmental factors, behavioral capability and hypertension MA in AA adults with MetS is needed.

Resistin is an adipocytokine derived from adipose tissue. Studies showed that resistin is not only related to insulin resistance, but also possibly an important factor related to activating of inflammation and atherosclerosis. It influences the endothelial cells and the function of vessel. To investigate whether or not resistin play a role in the metabolic syndrome and ischemic stroke. we examined the plasma resistin concentrations as well as the 3¡¦ untranslated region +62 G/A polymorphism of resistin gene in a Taiwan population. In the first part of this study, 112 patients with ischemic cerebral vascular disease and 110 healthy subjects were included and analyses of demographic and biochemical parameter, high sensitive C-reactive protein and plasma resistin concentration measurements were performed. In the second part, 594 patients with ischemic cerebral vascular disease and 799 healthy control were examined for resistin 3¡¦ untranslated region +62 G/A polymorphism. Resistin concentration was analyzed by EIA method, and resistin 3¡¦ untranslated region +62 G/A polymorphism was done by PCR and RFLP. The mean plasma resistin concentration of 112 patients with ischemic cerebral vascular disease was significantly lower than that of the 110 controls (32 ¡Ó 59.7 ng/ml and 55.7 ¡Ó 82.5 ng/ml, p < 0.001).When the concentration of resistin was divided into 4 groups and analyzed as continuous variable, it was found that decreased plasma resistin concentration is associated with increased risk of ischemic cerebral vascular disease. After the multiple adjustment by logistic analysis, the adds ratio for the first, second and third quadrate were 7.8, 5.0 and 0.1, respectively). The genotype analysis of 594 patients with ischemic cerebral vascular disease and 799 healthy controls show that the resistin genotype was related statistically to the risk of ischemic stroke. In multiple regression analysis, resistin 3¡¦ untranslated region +62 G/A polymorphism was significantly associated with diastolic blood pressure (GA + AA : GG = 142.2 ¡Ó 19.2 : 139.3 ¡Ó 20.7 mmHg, p = 0.044) and fasting plasma sugar (GA + AA : GG : 83.4 ¡Ó 13.1 : 81.1 ¡Ó 13.1 mg/dl , p = 0.005). Our results indicated that resistin may be related to metabolic syndrome and ischemic cerebral vascular disease and possibly play a role in the development of atherosclerosis.