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
Hany, M.; Demerdash, H.M.; Zidan, A.; Agayaby, A.S.S.; Torensma, B. 2022
Introduction Weight regain (WR) is described in approximately 30% of patient's post-bariatric surgery. It is related to the progression or recurrence of associated medical problems and decline in... Show moreIntroduction Weight regain (WR) is described in approximately 30% of patient's post-bariatric surgery. It is related to the progression or recurrence of associated medical problems and decline in health-related quality of life. This study aimed to test the return of body composition and metabolic biomarkers to pre-operative levels when WR occurs. Methods In this cross-sectional study conducted in 2021, patients were randomly selected from the hospital's electronic databases between 2001 and 2020. Patient demographic data, comorbidities, body compositions, and metabolic biomarkers were collected. Three groups were defined: groups A (WR), B (weight loss), and C (control group; patients with obesity who had not yet undergone bariatric surgery). Results A total of 88 patients were enrolled in this study and matched with the control group. The body mass index in group A was 43.8 +/- 6.9 kg/m(2); group B was 28.6 +/- 4.2; group C was 43.9 +/- 7.1. Body muscle mass, body fat mass, and visceral fat significantly differed between groups A and B (p < 0.001) but not between groups A and C (p = 0.8). There was a significant difference in leptin, ghrelin, postprandial glucagon-like peptide-1, insulin, and fibroblast growth factor-21 (but not retinol-binding protein-4) between groups A and B. Most metabolic biomarkers in group A returned to the pre-operative values as in group C. Conclusion WR had a direct negative effect on body composition and metabolic biomarkers, whereby the values returned to pre-operative levels. Early detection of WR and possible additional therapy are necessary to prevent associated medical problems. Show less
Akpinar, E.O.; Liem, R.S.L.; Nienhuijs, S.W.; Greve, J.W.M.; Marang-van de Mheen, P.J.; Dutch Audit Treatment Obesity Research Group 2022
Purpose: Hospitals performing a certain bariatric procedure in high volumes may have better outcomes. However, they could also have worse outcomes for some patients who are better off receiving... Show morePurpose: Hospitals performing a certain bariatric procedure in high volumes may have better outcomes. However, they could also have worse outcomes for some patients who are better off receiving another procedure. This study evaluates the effect of hospital preference for a specific type of bariatric procedure on their overall weight loss results. Methods: All hospitals performing bariatric surgery were included from the nationwide Dutch Audit for Treatment of Obesity. For each hospital, the expected (E) numbers of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB) were calculated given their patient-mix. These were compared with the observed (O) numbers as the O/E ratio in a funnel plot. The 95% control intervals were used to identify outlier hospitals performing a certain procedure significantly more often than expected given their patient-mix (defined as hospital preference for that procedure). Similarly, funnel plots were created for the outcome of patients achieving >= 25% total weight loss (TWL) after 2 years, which was linked to each hospital's preference. Results: A total of 34,558 patients were included, with 23,154 patients completing a 2-year follow-up, of whom 79.6% achieved >= 25%TWL. Nine hospitals had a preference for RYGB (range O/E ratio [1.09-1.53]), with 1 having significantly more patients achieving >= 25%TWL (O/E ratio [1.06]). Of 6 hospitals with a preference for SG (range O/E ratio [1.10-2.71]), one hospital had significantly fewer patients achieving >= 25%TWL (O/E ratio [0.90]), and from two hospitals with a preference for OAGB (range O/E ratio [4.0-6.0]), one had significantly more patients achieving >= 25%TWL (O/E ratio [1.07]). One hospital had no preference for any procedure but did have significantly more patients achieving >= 25%TWL (O/E ratio [1.10]). Conclusion: Hospital preference is not consistently associated with better overall weight loss results. This suggests that even though experience with a procedure may be slightly less in hospitals not having a preference, it is still sufficient to achieve similar weight loss outcomes when surgery is provided in centralized high-volume bariatric institutions. Show less
Hany, M.; Elfiky, S.; Mansour, N.; Zidan, A.; Ibrahim, M.; Samir, M.; ... ; Torensma, B. 2022
Purpose: To assess the effect of dialectical behavior therapy (DBT) on emotional and mindless eating and, consequently, body mass index (BMI) loss, in patients who have undergone bariatric surgery.... Show morePurpose: To assess the effect of dialectical behavior therapy (DBT) on emotional and mindless eating and, consequently, body mass index (BMI) loss, in patients who have undergone bariatric surgery. Materials and Methods: A prospective exploratory cohort study was conducted with two groups of patients who had undergone bariatric surgery: the DBT group received DBT group skills training sessions, while the control group received no intervention. Outcome measurements included BMI and scores of the Emotional Eating Scale (EES) and Mindful Eating Questionnaire (MEQ). Results: The study included 36 women: 18 in each group. In the DBT group, the interval from surgery was 11.17 +/- 7.12 months, and in the control group 10.89 +/- 5.74. Laparoscopic sleeve gastrectomy was done in 88.9% and 83.3% of patients in the DBT and control groups respectively. The rest underwent Roux-en-Y gastric bypass. The DBT group showed significant changes in overall and subscale scores of the EES and MEQ and BMI in kg/m(2) after 6 months of follow-up. BMI in kg/m(2) changed from mean +/- SD 35.45 +/- 6.17 to 28.47 +/- 4.28 in the DBT group, in control 35.88 +/- 5.07 to 31.56 +/- 3.71. The excess weight loss percentage (EWL%) in the DBT was mean +/- SD 75.3 +/- 17.9 and in the control was 63.6 +/- 14.5. In the DBT group, the EES score and MEQ score changed from mean +/- SD 45.06 +/- 20.19 to 20.50 +/- 13.40 and 11.52 +/- 2.02 to 15.87 +/- 1.92, respectively. The control group showed no significant change in scores. Conclusions: DBT skills training can reduce emotional eating, increase mindful eating, and facilitate weight loss after bariatric surgery. Show less
Janssen, L.G.M.; Nahon, K.J.; Bracké, K.F.M.; Broek, D. van den; Smit, R.; Mishre, A.S.D.S.; ... ; Rensen, P.C.N. 2020
Aims/hypothesis: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central... Show moreAims/hypothesis: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes.Methods: Twelve Dutch South Asian and 12 age- and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [F-18]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale.Results: Since the effect of exenatide onmetabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased bodyweight (-1.5 +/- 0.4 kg, p < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered tri-glycerides (-15%, p < 0.05) and total cholesterol (-5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([F-18]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI).Conclusions/interpretation: We show for the first time that GLP-1R agonism increases [F-18]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. (C) 2020 Elsevier Inc. All rights reserved. Show less
Janssen, L.G.M.; Nahon, K.J.; Bracke, K.F.M.; Broek, D. van den; Smit, R.; Mishre, A.S.D.S.; ... ; Rensen, P.C.N. 2020
Aims/hypothesis: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central... Show moreAims/hypothesis: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes.Methods: Twelve Dutch South Asian and 12 age- and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [F-18]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale.Results: Since the effect of exenatide onmetabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased bodyweight (-1.5 +/- 0.4 kg, p < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered tri-glycerides (-15%, p < 0.05) and total cholesterol (-5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([F-18]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI).Conclusions/interpretation: We show for the first time that GLP-1R agonism increases [F-18]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. (C) 2020 Elsevier Inc. All rights reserved. Show less
This thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients.... Show moreThis thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients. Because of the increasing number of patients with obesity and T2DM, more research is needed to identify patients at risk of developing T2DM and to elucidate specific therapeutic targets to improve insulin resistance. For now, the prevention of overweight and obesity is the most essential step in the fight against the worldwide obesity and T2DM epidemic Show less
Huisman, E.J.; Hoek, B. van; Soest, H. van; Nieuwkerk, K.M. van; Arends, J.E.; Siersema, P.D.; Erpecum, K.J. van 2012
The nuclear symptoms and signs of Huntington__s disease (HD) consist of motor, cognitive and behavioural disturbances. Other less well-known, but prevalent and debilitating features of HD include... Show moreThe nuclear symptoms and signs of Huntington__s disease (HD) consist of motor, cognitive and behavioural disturbances. Other less well-known, but prevalent and debilitating features of HD include unintended weight loss, sleep and circadian rhythm disturbances, as well as autonomic nervous system dysfunction. However, the pathogenesis of these less well-known features of HD is poorly understood and currently no effective treatment options are available. It is thus of paramount importance to elucidate the pathological basis of these symptoms and signs in order to design and apply more effective therapeutic interventions. Recently, substantial dysfunction of the hypothalamus was reported in both human studies and various knock-in and transgenic animal models of HD. The hypothalamus consists of groups of interconnected neuronal nuclei located at the base of the brain that regulate a broad array of physiologic, homeostatic and behavioural activities. Therefore, in this thesis we attempt to substantiate the premise that hypothalamic dysfunction per se, as well as secondary (neuro)endocrine and metabolic alterations could contribute to the pathogenesis of several non-motor symptoms and signs of HD. Show less
The evolutionary advantage to conserve energy in the form of adipose issue in order to survive long periods of food shortage in the past, turned into a major health problem in current times of... Show moreThe evolutionary advantage to conserve energy in the form of adipose issue in order to survive long periods of food shortage in the past, turned into a major health problem in current times of plenty. Excess accumulation of body fat, or "obesity", is associated with severely increased co-morbidity and mortality risks and is a global epidemical medical condition which is difficult to manage. The exact pathophysiologic mechanism of obesity remains elusive and various factors such as genetic, social, behavioral and physiological cues are involved in its development. From a biological point of view, obesity might be partly explained by differences in the regulation of energy intake, expenditure and storage (energy homeostasis) between obese and lean individuals. The neuroendocrine system provides a source of humoral messengers, which modulate energy homeostasis. This thesis will focus on changes of the neuroendocrine environment of obese women. First of all, spontaneous diurnal plasma hormone concentrations and secretion of different hormonal systems were studied. Secondly, the effect of weight loss on neuroendocrine perturbations of some of these hormonal axes was evaluated. Finally, the impact of modulation of potential physiological cues (increased circulating FFAs and deficit dopaminergic signaling), which might be involved in the neuroendocrine changes and metabolic alterations, was investigated. Show less
