With ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is... Show moreWith ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is increasingly recognised as a key modifiable cause. This thesis aims to investigate biological pathways between risk factors of cardiometabolic disease and cognitive function, in a population of older adults at increased risk of cardiovascular disease (CVD). We hypothesise that changes in physiological functioning caused by (sub)clinical CVD are possible mediators within the pathway leading to cognitive dysfunction. In the first part of this thesis, we studied electrocardiogram-based intervals and serum cardiac biomarkers (such as troponin) in relation to cognitive function. In the second part of this thesis, we studied the interplay of body mass index and serum leptin, loss of body weight and body weight variability, as well as metabolomics-based health scores in relation to cognitive function. We found that various cardiometabolic risk factors are associated with worse cognitive function. The results of this thesis strongly suggest that subclinical changes in cardiometabolic health may exist before cognitive dysfunction becomes apparent. Treating these cardiometabolic risk factors may be of benefit to future cognitive health. Show less
De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. Show less
Rapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate... Show moreRapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate the impacts of urbanization on human health, especially metabolic health and allergic disease, by incorporating many aspects of scientific investigation. Our cluster-randomized-controlled trial showed that, helminth infection, a characteristic feature of rural areas, and anthelmintic treatment, could significantly affect metabolic profiles and hormones. Thus, the ongoing deworming program in Indonesia require in parallel, monitoring of the metabolic health. Additionally, based on our prospective cohort study and analysis on a large scale nationally representative data, although Indonesian rural populations have relatively better metabolic profiles compared to urban, lifelong residence in rural areas does not protect their community members from adverse metabolic changes due to urbanization. Next, we observed that majority of individuals with diabetes in Indonesia were undiagnosed and untreated, especially in rural populations, which warrants extensive action plan from all related stakeholders. Lastly, high-dimensional data analyses on the systemic and nasal mucosal immune profiles revealed a stronger inflammatory immune responses in the nasal mucosal of Indonesian urban young adults with allergic rhinitis compared to their rural counterparts. Show less
In the first part of this thesis we focus on the genetic determinants of lipid metabolism as atherogenic dyslipidemia is major component of cardiometabolic disease and consequently of CVD. In the... Show moreIn the first part of this thesis we focus on the genetic determinants of lipid metabolism as atherogenic dyslipidemia is major component of cardiometabolic disease and consequently of CVD. In the second part of the thesis, we study the age-related changes of cardiometabolic risk factors over the life course across four generations. In this thesis, we aimed to gain new insights into the underlying pathophysiology of cardiometabolic disease and the long-term and cumulative exposure of its risk factors over the life course, thereby facilitating the search for preventive and curative strategies of cardiometabolic disease. In the first part of this thesis, we focused on the genetic determinants of lipid metabolism during both fasting and postprandial states. In the second part, we studied the age-related changes of cardiometabolic risk factors, in particular of body weight, overweight and obesity, over the life course across four generations. An important finding of the thesis is that obesity has worsened in the younger generations, reaching almost double the prevalence of older generations. However, after midlife the levels of obesity levelled off, which could be a reason why the adverse shift in obesity was not associated with unfavourable changes in cardiometabolic risk factors. We also found out that some genes effect body weight differently at different ages, which suggests that gene-environment interactions play an important role in body weight and consequently in obesity. Show less
Background Migraine is a highly prevalent disorder with significant economical and personal burden. Despite the development of effective therapeutics, the causes which precipitate migraine attacks... Show moreBackground Migraine is a highly prevalent disorder with significant economical and personal burden. Despite the development of effective therapeutics, the causes which precipitate migraine attacks remain elusive. Clinical studies have highlighted altered metabolic flux and mitochondrial function in patients. In vivo animal experiments can allude to the metabolic mechanisms which may underlie migraine susceptibility. Understanding the translational relevance of these studies are important to identifying triggers, biomarkers and therapeutic targets in migraine. Main body Functional imaging studies have suggested that migraineurs feature metabolic syndrome, exhibiting hallmark features including upregulated oxidative phosphorylation yet depleted available free energy. Glucose hypometabolism is also evident in migraine patients and can lead to altered neuronal hyperexcitability such as the incidence of cortical spreading depression (CSD). The association between obesity and increased risk, frequency and worse prognosis of migraine also highlights lipid dysregulation in migraine pathology. Calcitonin gene related peptide (CGRP) has demonstrated an important role in sensitisation and nociception in headache, however its role in metabolic regulation in connection with migraine has not been thoroughly explored. Whether impaired metabolic function leads to increased release of peptides such as CGRP or excessive nociception leads to altered flux is yet unknown. Conclusion Migraine susceptibility may be underpinned by impaired metabolism resulting in depleted energy stores and altered neuronal function. This review discusses both clinical and in vivo studies which provide evidence of altered metabolic flux which contribute toward pathophysiology. It also reviews the translational relevance of animal studies in identifying targets of biomarker or therapeutic development. Show less
OBJECTIVES: The objective was to analyse associations between obesity and outcomes after left ventricular assist device (LVAD) implantation.METHODS: A retrospective analysis of the EUROMACS... Show moreOBJECTIVES: The objective was to analyse associations between obesity and outcomes after left ventricular assist device (LVAD) implantation.METHODS: A retrospective analysis of the EUROMACS Registry was performed. Adult patients undergoing primary implantation of a continuous-flow LVAD between 2006 and 2019 were included (Medtronic HeartWare((R)) HVAD((R)), Abbott HeartMate II (R), Abbott HeartMate 3 (TM)). Patients were classified into 4 different groups according to body mass index at the time of surgery (body mass index <20 kg/m(2): n = 254; 20-24.9 kg/m(2): n = 1281; 25-29.9 kg/m(2): n = 1238; >= 30 kg/m(2): n = 691).RESULTS: The study cohort was comprised of 3464 patients. Multivariable Cox proportional cause-specific hazards regression analysis demonstrated that obesity (body mass index >= 30 kg/m(2)) was independently associated with significantly increased risk of mortality (body mass index >= 30 vs 20-24.9 kg/m(2): hazard ratio 1.36, 95% confidence interval 1.18-1.57, overall P < 0.001). Moreover, obesity was associated with significantly increased risk of infection and driveline infection. The probability to undergo heart transplantation was significantly decreased in obese patients (body mass index >= 30 vs 20-24.9 kg/m(2): hazard ratio 0.59, 95% confidence interval 0.48-0.74, overall P < 0.001).CONCLUSIONS: Obesity at the time of LVAD implantation is associated with significantly higher mortality and increased risk of infection as well as driveline infection. The probability to undergo heart transplantation is significantly decreased. These aspects should be considered when devising a treatment strategy before surgery. Show less
Overweight and obesity are abnormal or excessive body fat accumulation that presents a risk to health. The World Health Organisation defines overweight and obesity with the Body Mass Index (BMI)... Show moreOverweight and obesity are abnormal or excessive body fat accumulation that presents a risk to health. The World Health Organisation defines overweight and obesity with the Body Mass Index (BMI) classification, which is a measure of a person’s weight in kilograms (kg) divided by the square of height in meters (m2). Overweight is defined as a BMI of 25 kg/m2 or higher, whereas obesity is defined as a BMI of 30 kg/m2 or higher. It is estimated that one of every three individuals in the global population has overweight. The prevalence of obesity is increased threefold from 1975 to 2016, with a faster-growing pace in low- and middle-income countries than high-income countries. One common complication of obesity is the metabolic syndrome, which is defined as the co-occurrence of at least three out of five cardiometabolic abnormalities (abdominal obesity, hypertension, hyperglycaemia, hypertriglyceridemia, and low HDL-cholesterol). The metabolic syndrome is a strong risk factor for type 2 diabetes and cardiovascular diseases, and is considered a pathway from obesity to the cardiometabolic diseases occurrence. Thus, if metabolic syndrome or its components are identified and treated early, type 2 diabetes and cardiovascular diseases may be prevented. In this multi-ethnic global population, it is well-established that different ethnic populations have different cardiometabolic risks. Studies have shown that Asian populations develop cardiometabolic complications earlier at the same amount of adiposity as the Western populations. Show less
Background: Hand osteoarthritis (HOA) is a highly prevalent rheumatic disease that predominates in females and causes pain and loss of functional capacity. Obesity and metabolic syndrome have been... Show moreBackground: Hand osteoarthritis (HOA) is a highly prevalent rheumatic disease that predominates in females and causes pain and loss of functional capacity. Obesity and metabolic syndrome have been previously suggested to associate with the severity of HOA, but clarity on these associations is yet to be achieved.Objective: Test the association between obesity and other components of the metabolic syndrome and disability in women with hand osteoarthritis (HOA).Design: Individuals from EpiReumaPt epidemiological community-based study (2011-2013) are representative of the Portuguese population. Women with diagnosis of primary HOA were included.Primary outcome: hand functional status, assessed by Cochin questionnaire.Secondary outcomes: hand pain, assessed by visual analogue scale and tender hand joint count (THJ).Explanatory variables: obesity, diabetes mellitus, arterial hypertension and hypercholesterolemia. Possible associations between obesity and the other components of metabolic syndrome with Cochin score, hand pain and THJ were tested in a multivariable linear regression model.Potential confounders considered: age, education level and countrywide distribution.Results: 473 women with primary HOA were included. Forty percent were overweight and 29% obese. Ninety-three (19.8%) participants had diabetes, 261 (55.8%) reported hypertension and 261 (55.9%) hypercholesterolemia. Mean Cochin score was 15.5 +/- 14.8, mean pain VAS was 4.7 +/- 2.6 and mean THJ 1.4 +/- 3. In the multivariable analysis, obesity (beta 4.6 CI 0.7;8.5) and diabetes (beta 4.0 CI 0.4;7.6) were found to significantly associate with HOA functional disability. In addition, diabetes, but not obesity, associated with hand pain. There was no association between obesity or diabetes with THJ.Conclusion: In a Portuguese female population with primary HOA, obesity and diabetes mellitus independently associated with a worse hand functional status. These data add to evidence suggesting a role of metabolic factors in the severity of HOA. Show less
Heparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune... Show moreHeparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune diabetes is well documented, its association with metabolic syndrome/type 2 diabetes attracted less attention. Our research was undertaken to elucidate the significance of heparanase in impaired glucose metabolism in metabolic syndrome and early type 2 diabetes. Here, we report that heparanase exerts opposite effects in insulin-producing (i.e., islets) vs. insulin-target (i.e., skeletal muscle) compartments, sustaining or hampering proper regulation of glucose homeostasis depending on the site of action. We observed that the enzyme promotes macrophage infiltration into islets in a murine model of metabolic syndrome, and fosters beta-cell-damaging properties of macrophages activated in vitro by components of diabetogenic/obese milieu (i.e., fatty acids). On the other hand, in skeletal muscle (prototypic insulin-target tissue), heparanase is essential to ensure insulin sensitivity. Thus, despite a deleterious effect of heparanase on macrophage infiltration in islets, the enzyme appears to have beneficial role in glucose homeostasis in metabolic syndrome. The dichotomic action of the enzyme in the maintenance of glycemic control should be taken into account when considering heparanase-targeting strategies for the treatment of diabetes. Show less
Objective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF ... Show moreObjective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF (< 3 months) with >= 1 stroke risk factors enrolled in the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) in Asia, Europe and North America were evaluated.Results: The cohort (n = 13,793) comprised patients from all BMI categories (kg/m(2)): 1.4% were underweight (<18.5), 27.3% had a normal BMI (18.5 to <25), 37.9% were overweight (25 to <30), 19.3% were moderately obese (30 to < 35), and 12.7% were morbidly obese (>= 35). The highest proportion of Asians had a BMI of 18.5 to <25 kg/m(2), while the highest proportion of patients from Europe and North America were overweight and a substantial proportion of North Americans morbidly obese. In the multivariable analysis, the probability ratio of non-prescription of OAC, as compared to normal BMI, decreased for overweight (RR = 0.907), moderately obese (RR = 0.802) and severe very severe obese patients (RR = 0.659). Moreover, the probability ratio of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe, in patients aged <65 years or female patients, as well as in patients with prior bleeding or vascular disease.Conclusions: The distribution of BMI differed among the continents. An increased BMI was associated with a lower probability of non-prescription of OACs, as compared with a normal BMI. The probability of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe. Show less
Kroon, F.P.B.; Veenbrink, A.I.; Mutsert, R. de; Visser, A.W.; Dijk, K.W. van; Cessie, S. le; ... ; Kloppenburg, M. 2019
Background & aims: Obesity is a well-established risk factor of vitamin D deficiency. However, it is unclear which fat deposit is most strongly related to serum 25-hydroxyvitamin D (25(OH)D)... Show moreBackground & aims: Obesity is a well-established risk factor of vitamin D deficiency. However, it is unclear which fat deposit is most strongly related to serum 25-hydroxyvitamin D (25(OH)D) concentrations. Our aim was to distinguish the specific contributions of total body fat (TBF), abdominal subcutaneous adipose tissue (aSAT), visceral adipose tissue (VAT) and hepatic fat on 25(OH)D concentrations.Methods: We performed a cross-sectional analysis of the Netherlands Epidemiology of Obesity study, a population-based cohort study. We used linear regression analyses to examine associations of TBF, aSAT, VAT (n = 2441) and hepatic fat (n = 1980) with 25(OH)D concentrations. Standardized values were used to compare the different fat deposits.Results: Mean (SD) age and 25(OH)D concentrations of the study population was 56 (6) years and 70.8 (24.2) nmol/L, respectively. TBF was inversely associated with 25(OH)D concentrations in women, but not in men. One percent higher TBF was associated with 0.40 nmol/L (95%CI: -0.67 to -0.13) lower 25(OH)D. aSAT was not associated with 25(OH)D concentrations. One cm 2 higher VAT was associated with 0.05 nmol/L (-0.09 to -0.02) lower 25(OH)D in men, and 0.06 nmol/L (-0.10 to -0.01) lower 25(OH)D in women. Hepatic fat was only associated with 25(OH)D in men. A tenfold increase in hepatic fat was associated with 6.21 nmol/L (-10.70 to -1.73) lower 25(OH)D. Regressions with standardized values showed VAT was most strongly related to 25(OH)D.Conclusions: In women, TBF and VAT were inversely related to 25(OH)D concentrations. In men, VAT and hepatic fat were inversely related to 25(OH)D concentrations. In both groups, VAT was most strongly associated with 25(OH)D concentrations. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Show less
Aims/hypothesis Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in... Show moreAims/hypothesis Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in rodents. This study aimed to evaluate the associations between plasma levels of these metabolites and adiposity and metabolic profile in humans. Methods Fasting plasma succinate and 12,13-diHOME levels were quantified using ultra HPLC-tandem MS in 2248 individuals (50% female, mean age 41.3 +/- 5.9 years, mean BMI 26.1 +/- 4.6 kg/m(2)) in addition to fasting plasma biochemistry. Total and regional adiposity were assessed with dual-energy x-ray absorptiometry. An age- and sex-adjusted linear regression model was used to determine the associations between succinate and 12,13-diHOME levels and body composition and metabolic profile. Two-sample Mendelian randomisation was used to assess the associations between genetically determined BMI and metabolic traits with circulating plasma succinate and 12,13-diHOME. Results A one-SD higher plasma succinate and 12,13-diHOME concentration was associated with a 0.15 SD (95% CI 0.28, 0.03) and 0.08 SD (0.15, 0.01) lower total fat mass respectively. Additionally, a one-SD higher plasma 12,13-diHOME level was associated with a 0.09 SD (0.16, 0.02) lower fasting plasma insulin and 0.10 SD (0.17, 0.04) lower plasma triacylglycerol. In Mendelian randomisation analyses, genetically determined higher BMI, fasting hyperinsulinaemia and elevated lipid levels were not associated with changes in either plasma succinate or plasma 12,13-diHOME concentrations. No indications of bias due to directional pleiotropy were detected in the Mendelian randomisation analyses. Conclusions/interpretation Our findings tentatively suggest that plasma succinate and 12,13-diHOME may play a role in the regulation of energy metabolism and brown adipose tissue activation in humans. Further studies encompassing direct assessment of brown adipose tissue activity and dietary supplementation are necessary to investigate the potential beneficial effects of these metabolites on systemic metabolism. Show less
Introduction We investigated improvement of electrocardiographic LVH detection by adding measures of adiposity and/or novel electrocardiographic measures. Left ventricular hypertrophy (LVH) is an... Show moreIntroduction We investigated improvement of electrocardiographic LVH detection by adding measures of adiposity and/or novel electrocardiographic measures. Left ventricular hypertrophy (LVH) is an important risk factor for adverse cardiovascular outcomes. Improvement of electrocardiographic criteria for LVH is desirable, since electrocardiography is widely used. Methods We included 1091 participants of the Netherlands Epidemiology of Obesity Study (NEO) who underwent cardiac magnetic resonance imaging (MRI). Performance of Sokolow-Lyon and Cornell voltage and product criteria was assessed. Stepwise regression analysis was performed with each conventional electrocardiographic criterion and age, sex, body mass index (BMI), waist circumference, and waist:hip ratio (p-entry < 0.05, p-removal > 0.10). T-wave abnormalities or the spatial QRS-T angle (SA) were added to the improved models. Results The study population had a mean (SD) age of 56 (6) years, BMI of 26.1 (4.0) kg/m(2) and 46% were men. MRI-LVH was present in 10% of participants. The c-statistic for Sokolow-Lyon voltage was 0.58, R-2 was 0.02 and sensitivity at 90% specificity was 16%, for Sokolow-Lyon product this was 0.62, 0.02, and 21%, for Cornell voltage 0.65, 0.04, and 28% and for Cornell product 0.67, 0.04, and 25%. Best performing models were obtained by addition of both BMI and SA (Sokolow-Lyon voltage: c-statistic 0.74, R-2 0.11, sensitivity of 41% at 90% specificity; Sokolow-Lyon product: 0.75, 0.12, 42%; Cornell voltage: c-statistic 0.70, R-2 0.08, sensitivity of 38% at 90% specificity; Cornell product: c-statistic 0.72, R-2 0.08, sensitivity of 44% at 90% specificity). Conclusions Electrocardiographic detection of LVH improved by adding BMI and SA to a model with conventional electrocardiographic criteria. This approach would require little extra effort and application in clinical practice is feasible. However, results should first be replicated in high-risk populations. Show less
Background & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity.... Show moreBackground & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity. However, there is a lack of consensus regarding the method of choice to analyze indirect calorimetry data from a CIT study. We analyzed the impact of methods for data selection and methods for data analysis on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates.Methods: Forty-four young healthy adults (22.1 +/- 2.1 years old, 25.6 +/- 5.2 kg/m(2), 29 women) participated in the study. Resting metabolic rate (RMR), cold-induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were estimated by indirect calorimetry under fasting conditions during 1 h of cold exposure combining air conditioning (19.5-20 degrees C) and a water perfused cooling vest set at a temperature of 4 degrees C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5 min (5min-TI), (ii) the most stable 5-min period of every forth part of the cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half part of the cold exposure (5min-SS-2P). Lately we applied two methods for data analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and; (ii) the difference between EE at the end of the cold exposure and baseline RMR (Last-RMR).Results: Mean overall CIT estimation ranged from 11.6 +/- 10.0 to 20.1 +/- 17.2 %RMR depending on the methods for data selection and analysis used. Regarding methods for data selection, 5min-SS-2P did not allow to observe physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P = 0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data selection seemed to be accurate enough to observe physiologically relevant phenomena (all P < 0.014), but not comparable for estimating over-all CIT and cold-induced nutrient oxidation rates (P < 0.01). Regarding methods for data analysis, the AUC seemed to be less affected for data artefacts and to be more representative in participants with a non-stable energy expenditure during cold exposure.Conclusions: The methods for data selection and analysis can have a profound impact on CIT and cold-induced nutrient oxidation rates estimations, and therefore, it is mandatory to unify it across scientific community to allow inter-study comparisons. Based on our findings, 5min-TI should be considered the method of choice to study dynamics (i.e. changes across time) of CIT and cold-induced nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice when computing CIT and cold-induced nutrient oxidation rates as a single value. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Show less
Turk, Y.; Sin, H.K.; Huisstede, A. van; Birnie, E.; Biter, U.; Hiemstra, P.S.; Braunstahl, G.J. 2019
Morbidly obese subjects with airflow obstruction who underwent laparoscopic bariatric surgery appear to have the greatest risk to develop complications. In a retrospective cohort study, we... Show moreMorbidly obese subjects with airflow obstruction who underwent laparoscopic bariatric surgery appear to have the greatest risk to develop complications. In a retrospective cohort study, we identified a waist circumference >= 120 cm, smoking history >= 5PY and history of obstructive lung disease as statistically significant predictors of airflow obstruction. The resulting algorithm, aimed to identify subjects with airflow obstruction before bariatric surgery, was validated in a prospective study. The algorithm was found to be effective in identifying patients with low risk of airflow obstruction (negative predictive value 94.7%). Airflow obstruction, however, was not associated with post-operative complications as we expected. In contrast, inspiratory capacity and the Epworth Sleepiness scale were more promising predictors for post-operative complications in subjects undergoing bariatric surgery. Show less
Christen, T.; Trompet, S.; Rensen, P.C.N.; Dijk, K.W. van; Lamb, H.J.; Jukema, J.W.; ... ; Mutsert, R. de 2019
Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In... Show moreChildhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In children with obesity and respiratory symptoms the diagnosis of asthma was studied and in children with ADHD dosing regimens. Overtreatment as a consequence of overdiagnosis was frequently observed in children with obesity and asthma and undertreatment due to relative underdosing in the ADHD population with obesity. This highlights the necessity for accurate diagnostic processes alongside dosing regimens based on pharmacokinetic changes caused by obesity. The focus in the second part of this thesis was on screening for complications of obesity namely insulin resistance and cardiovascular diseases. Given the high prevalence of insulin resistance and the observed changes of cardiovascular parameters, screening on cardiometabolic complications is warranted in all children with obesity. Pharmacological treatment with metformin in addition to lifestyle intervention was studied in the last part of this thesis. Given the favorable effect on BMI in children and adults and the maintenance of weight loss and reduction in progression towards T2DM in adults, metformin can be considered in children with obesity and insulin resistance in addition to lifestyle intervention. Show less
