Browsing by Subject "Metabolic syndrome"

Now showing 1 - 3 of 3
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    An Apple from the Tree? A Look at Cardiometabolic Risk Factors in Parents and Offspring
    (2015-06) Halvorsen, Tanya
    Objectives: To relate parental cardiometabolic risk factors with corresponding values in their children and assess the influence of adiposity on these associations. Study Design: Associations of adiposity, blood pressure, lipids, fasting insulin and glucose, and a risk factor cluster score were evaluated in a cross sectional study of 179 parents and their children (6-18 years, N=255). Insulin resistance was assessed by euglycemic clamp in parents and children aged 10 or older. Metabolic syndrome in parents was defined by ATPIII criteria. Cluster scores of the risk factors were created based on age-specific z-scores. Analyses included Pearson correlation and linear regression, adjusted for parent and child age, sex, race, and body mass index (BMI), accounting for within-family correlation. Results: We found positive parent-child correlations for measures of adiposity (BMI, BMI percentile, waist, subcutaneous fat, and visceral fat; r=0.22-0.34, all p≤0.003), systolic blood pressure (SBP) (r=0.20, p=0.002), total cholesterol (r=0.39, p<0.001), low-density lipoprotein cholesterol (r=0.34, p<0.001), high density lipoprotein cholesterol (r=0.26, p<0.001) triglycerides (r=0.19, p=0.01) and insulin sensitivity (r=0.22, p=0.02) as well as cluster scores (r=0.15, p=0.02). After adjustment for BMI all parent-child correlations, except systolic blood pressure, remained significant. Conclusions: Although adiposity is strongly correlated between parents and children, many cardiometabolic risk factors correlate independent of parent and child BMI. Adverse parental cardiometabolic profiles may identify at-risk children independent of the child’s adiposity status.
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    Atrial fibrillation: relation to the metabolic syndrome, smoking, and development of a clinical risk score.
    (2009-11) Chamberlain, Alanna Marie
    This document provides information on the pathophysiology and epidemiology of atrial fibrillation, along with details on three manuscripts that together form the basis of a doctoral thesis. Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and poses a great economic burden on the healthcare system. Some well known cardiovascular risk factors, such as smoking and the metabolic syndrome, have not been widely studied in the context of AF. In addition, the majority of studies on AF have used primarily white cohorts from North America and Europe. This dissertation reports the associations of the metabolic syndrome and smoking with incident AF, and provides a 10-year risk prediction score for AF using the Atherosclerosis Risk in Communities (ARIC) study. The ARIC study is a bi-racial cohort of almost 16,000 participants followed since the baseline examination in 1987-1989. The first manuscript describes the association of the metabolic syndrome and the individual components of the metabolic syndrome with risk of incident AF over a mean follow-up of 15.4 years. A 67% increased risk of incident AF was reported for individuals with compared to those without the metabolic syndrome at baseline. Most of the metabolic syndrome components were associated with an increased AF risk, and of the individual components, elevated blood pressure appeared to contribute most to AF risk. In addition, a monotonically increasing risk of AF with increasing number of metabolic syndrome components was observed. In the second manuscript, the associations of smoking status and amount with incident AF in ARIC were examined, and a systematic literature review on prospective cohort studies investigating the effects of smoking on AF incidence was conducted. Current and former smokers exhibited a 98% and 30% increased risk of developing AF compared to never smokers. The risk of incident AF increased with increasing cigarette-years of smoking, and appeared to be somewhat greater among current smokers than former smokers with similar cigarette-years of smoking. However, no consistent association was apparent in previously published studies on smoking and incident AF. A 10-year risk score for AF was developed using risk factors commonly measured in clinical practice for the third manuscript. The risk score had good discrimination and better predicted who would develop AF than the Framingham AF risk score applied to the ARIC cohort. In addition, the Framingham and ARIC coronary heart disease risk scores did not predict the 10-year risk of AF well, highlighting the importance of a separate risk score to predict AF.
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    The Functional Role of Receptor-Interacting Protein 140 (RIP140) in Innate Immunity and Metabolic Syndrome
    (2016-12) Lin, Yi-Wei
    Metabolic diseases, such as type II diabetes (T2DM), atherosclerosis and other cardiovascular diseases, are prevalent and are important health issues in the modern world. T2DM contributes to the development of various metabolic diseases. Atherosclerosis is one of the major causes leading to multiple cardiovascular diseases. In order to develop therapeutic strategies, understanding the mechanisms of these metabolic diseases is crucial. It is known that the immune system is highly involved in initiation and progression of metabolic diseases. Macrophages are one of the major leukocytes in innate immunity. Macrophages have two major polarized phenotypes: classical/pro-inflammatory (M1) and alternative/anti-inflammatory (M2). It is widely accepted that M1-M2 switch in macrophage population is essential in disease progression or damage recovery; however, the detailed mechanism of macrophage phenotype switch has not been fully elucidated. In addition, the effect of altering the macrophage phenotype on treating metabolic diseases remains uncertain. Receptor-interacting protein 140 (RIP140) is a co-regulator of numerous nuclear receptors and transcription factors. RIP140 is expressed in various cell types including adipocytes, liver, muscle, heart, neurons, and cells in the monocyte–macrophage lineage. Studies showed that RIP140 expression is positively associated with the progression of metabolic disorders such as obesity, insulin resistance, and glucose intolerance. In addition, studies indicate that RIP140 acts as a co-activator of NFκB to promote macrophage M1 activation and pro-inflammatory responses. My studies further build on this knowledge to uncover the role of RIP140 in the metabolic diseases. First, it was found that RIP140 elevates cholesterol content in macrophages by reducing expression of ABC transporters, which are responsible for cholesterol efflux. The elevated cytosolic cholesterol induces foam cell formation and further enhances progression of atherosclerosis. This study indicated that reducing RIP140 levels effectively ameliorates high-cholesteroldiet-induced atherosclerosis. Second, my study found that reducing RIP140 in macrophages leads to macrophage M2 polarization, resulting in adipose tissue remodeling to brown/beige adipose tissue. This further ameliorates high fat diet-induced T2DM associated metabolic disorders. Moreover, later studies address how RIP140 mediates macrophage M2 activation and M1/M2 switch by its cytosolic function in a wound healing animal model. Final study is to identify a beneficial taxonomic repertoire from macrophage specific RIP140 knockdown (MφRIP140KD) mice. Fecal microbiota transplantation (FMT) from HFD-fed MφRIP140KD to wild type (WT) mice acquired the benefits from donors, which is resistant to development of HFD-induced metabolic diseases. Taken together, this thesis studies elucidate novel functions of RIP140 in polarization and inflammatory responses in macrophages, and identify the benefits of reducing RIP140 expression in macrophages. These findings contribute to our understanding of the relationship between immune and metabolic systems as well as provide a therapeutic target of resolving inflammation and preventing/improving metabolic profiles in T2DM, and atherosclerosis.