Aims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with... Show moreAims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. Methods: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. Results: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolicload factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. Conclusion: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased leftventricular diastolic function, more apparent in females than in males. Show less
Meulmeester, F.L.; Luo, J.; Martens, L.G.; Ashrafi, N.; Mutsert, R. de; Mook-Kanamori, D.O.; ... ; Noordam, R. 2021
Background and aims: The accumulation of fat increases the formation of lipid perox-ides, which are partly scavenged by alpha-tocopherol (a-TOH). Here, we aimed to investigate the associations... Show moreBackground and aims: The accumulation of fat increases the formation of lipid perox-ides, which are partly scavenged by alpha-tocopherol (a-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary a-TOH metab-olites in middle-aged individuals. Methods and results: In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N Z 511, 53% women; mean [SD] age of 55 [6.1] years), serum a-TOH and a-TOH metab-olites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (a-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (a-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were as-sessed using magnetic resonance imaging. Using multivariable-adjusted linear regression ana -lyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary a-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum a-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. Conclusions: Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized a-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
The aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as... Show moreThe aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as adipokines, inflammation, HDL-cholesterol and postprandial triglyceride response, and cholesteryl ester transfer protein (CETP). We showed that hs-CRP and GlycA as measures of inflammation, adiponectin, and leptin are not associated with clinical and subclinical cardiovascular disease in the general population. However, all may be relevant markers of disease risk. Also, postprandial triglyceride excursions, genetically-determined CETP and HDL-cholesterol, while not related with subclinical atherosclerosis in the general population, may be interesting targets to pursue in women and men separately, and in subgroups of individuals at high-cardiovascular risk. Show less
The prevalence of obesity is increasing worldwide. In particular abdominal obesity is a well-established risk factor for cardiometabolic diseases. The excess risk of abdominal obesity is due to fat... Show moreThe prevalence of obesity is increasing worldwide. In particular abdominal obesity is a well-established risk factor for cardiometabolic diseases. The excess risk of abdominal obesity is due to fat in the visceral area and in and around the organs (ectopic fat), such as in the liver. The main aim of this thesis was therefore to study whether lifestyle can reduce the amount of visceral fat and liver fat.Firstly, in a systematic review and meta-analysis of randomized controlled trials, we concluded that a diet high in proteins decreases liver fat compared with a diet high in carbohydrates. A diet high in fat did not lead to changes in liver fat compared with a diet high in carbohydrates. Within fat types, saturated fat leads to more liver fat accumulation than unsaturated fat. Secondly, we studied diet at multiple levels in the Netherlands Epidemiology of Obesity study, which is a population based cohort study of middle-aged men and women with directly assessed measured of adiposity. When studying food groups rather than nutrients, we observed that consumption of sweet snacks are positively associated with liver fat content, also after taking into account total body fat. Likewise, consumption of fruit and vegetables and plant-based fats and oils was associated with less visceral fat. A better adherence to the current Dutch dietary guidelines, as indicated by a higher score on the 15-component Dutch Healthy Diet Index, was associated with less total body fat, less visceral fat and liver fat. The associations with visceral fat and liver fat remained present after taking into account total body fat, indicating that the associations are indeed specific for visceral and liver fat rather than merely representing associations with overall adiposity. Associations were not driven by one component in particular, indicating the importance of an overall healthy diet. When we studied alcohol intake separately, each additional serving of alcoholic beverages per day was also associated with more liver fat. Moreover, replacing one alcoholic serving with one non-alcoholic serving was associated with less liver fat. Replacing the same amount of calories of alcoholic beverages with sugar sweetened beverages was equally associated with liver fat, whereas replacement with milk was associated with less liver fat. Lastly, we observed that objectively measured sedentary time was associated with more total body fat, visceral fat and liver fat. Replacing 30 minutes of sedentary time per day with moderate to vigorous physical activity, but not light physical activity was associated with less total body fat, visceral fat and liver fat. These associations with visceral fat and liver fat disappeared after additional adjustment for total body fat, indicating that there is no extra effect on visceral fat and liver fat beyond effects via total body fat.Results described in this thesis hint towards the importance of considering diet as a whole, instead of separate components, which is in line with the current dietary guidelines. Sedentary behaviour should be replaced with moderate to vigorous physical activity rather than light physical activity. Alcohol should not be replaced with sugar sweetened beverages, but rather with milk, coffee or tea. Show less
In this thesis, the importance of visceral obesity in the relation of obesity with cardiometabolic risk factors (chapter 2) was confirmed and it was shown that in individuals free of known... Show moreIn this thesis, the importance of visceral obesity in the relation of obesity with cardiometabolic risk factors (chapter 2) was confirmed and it was shown that in individuals free of known cardiovascular disease clustering of cardiometabolic risk factors is associated with changes in electrocardiographic parameters indicative of subclinical cardiovascular disease (chapter 3). The findings from chapter 3 also point to the importance of the prevention of these metabolic syndrome components, not only in obese, but also in non-obese individuals. Furthermore, both overall and abdominal adiposity were found to be associated with these deleterious changes in electrocardiographic parameters (chapter 4). Borderline Q-waves were associated with a negative cardiovascular risk profile and increased pulse wave velocity and intima-media thickness (chapter 5). Chapter 6 shows that several cardiovascular risk factors were associated with a wider spatial QRS-T angle, which reflects ventricular electrophysiological heterogeneity. Both carotid intima-media thickness, as measure of subclinical atherosclerosis, and pulse wave velocity, as measure of arterial stiffness, were associated with a wider spatial QRS-T angle. In chapter 7, improvement of electrocardiographic detection of left ventricular hypertrophy with conventional electrocardiographic criteria by taking into account body mass index and the spatial QRS-T angle is shown. Show less
Worldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of... Show moreWorldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of preventive and curative strategies for cardiometabolic disease is eagerly warranted. With the studies describes in this thesis, we aimed to disentangle the interwoven physiological, environmental and genetic factors that determine cholesterol and energy metabolism to increase our understanding of their contribution to cardiometabolic disease risk. The first part of this thesis focussed on the cholesteryl ester transfer protein (CETP). The lipid transfer properties of CETP induce a proatherogenic lipoprotein profile. Therefore, CETP inhibitory molecules have been developed and tested in clinical trials for their capability to improve the lipoprotein profile and reduce CVD risk. To fully understand the role of CETP in CVD, its physiology and biological function should be fully unravelled. The focus of the second part of this thesis was on the role of energy metabolism in cardiometabolic health. Specifically, we aimed to study the association of environmental and genetic factors, which were previously described to influence brown adipose tissue (BAT) activity, with energy expenditure and disease outcomes. Show less
Garessus, E.D.G.; Mutsert, R. de; Visser, A.W.; Rosendaal, F.R.; Kloppenburg, M. 2016
Conclusion: An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the... Show moreConclusion: An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the presence of sex differences in the pathogenesis of hand OA. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Gast, K.B.; Heijer, M. den; Smit, J.W.A.; Widya, R.L.; Lamb, H.J.; Roos, A. de; ... ; NEO Study Grp 2015
This thesis focuses on the incidence and risk factors for nephropathy in diabetic and non-diabetic Surinamese South Asians. The Surinamese South Asians, originally descended from the North-East... Show moreThis thesis focuses on the incidence and risk factors for nephropathy in diabetic and non-diabetic Surinamese South Asians. The Surinamese South Asians, originally descended from the North-East India. Due to the former colonial bounds with the Netherlands, a relatively young South Asian migrant population settled in the Netherlands. South Asians have a high prevalence of central obesity and an eight-fold higher prevalence for type 2 diabetes mellitus. We found the following conclusions: 1.Surinamese South Asian persons have a nearly 40-fold higher risk for end-stage diabetic nephropathy in comparison to Dutch European persons. 2.There was no familial predisposition for diabetic nephropathy among South Asian families. 3.South Asian type 2 diabetic patients have a three-fold higher risk for diabetic nephropathy and faster progression of renal insufficiency in comparison to Dutch European patients. 4.Central obesity is an early and independent risk factor for increased albuminuria in normoglycemic South Asian subjects. We assume that the nearly 40-fold higher risk of end-stage diabetic nephropathy in South Asian migrants is primarily caused by central obesity which leads to: a. Early renal injury in the pre-diabetic state. b. Eight-times higher prevalence of type 2 diabetes mellitus. b. More diabetic nephropathy and faster decline in renal function. Show less
