Background and aim: Non-alcoholic fatty liver disease (NAFLD) is defined as a liver fat content >= 5.56%. It is of clinical interest to know the prevalence of NAFLD in people with a combination... Show moreBackground and aim: Non-alcoholic fatty liver disease (NAFLD) is defined as a liver fat content >= 5.56%. It is of clinical interest to know the prevalence of NAFLD in people with a combination of metabolic risk factors. We aimed to examine the prevalence of NAFLD, including groups with metabolic risk factors.Methods and results: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, liver fat content was assessed using proton magnetic resonance spectroscopy (H-MRS). Participants with excessive alcohol consumption or missing values were excluded, leaving a total of 1570 participants for the analyses. Mean (SD) age of the population was 55 years, BMI 25.9 (4.0) kg/m(2) and 46% were men. The prevalence of NAFLD was 27% (95% CI 24-30). The prevalence of NAFLD was increased in participants with hypertriglyceridemia (57%, 52-63), obesity (62%, 58-66) and diabetes (69%, 61-77). The prevalence of NAFLD was highest in those with diabetes and obesity (79%, 71-87), obesity and hypertriglyceridemia (81%, 76-86) and with diabetes and hypertriglyceridemia (86%, 77-95). NAFLD was also present in 12% (8-16) of participants without overweight.Conclusions: The prevalence of NAFLD in a middle-aged population in the Netherlands in 2010 was 27%. The prevalence of NAFLD is particularly increased in individuals with diabetes, obesity, and hypertriglyceridemia. This information may help clinicians and general practitioners in the risk stratification of their patients in daily practice.(c) 2023 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
BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic... Show moreBackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands’ immunometabolic health on siblings’ psychological symptoms and on the association between immunometabolic health and these symptoms in siblings.MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering.ResultsIn siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings.ConclusionsOur findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health. Show less
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
Kroon, J.; Viho, E.M.G.; Gentenaar, M.; Koorneef, L.L.; Kooten, C. van; Rensen, P.C.N.; ... ; Meijer, O.C. 2021
Glucocorticoids regulate numerous processes in human physiology, but deregulated or excessive glucocorticoid receptor (GR) signaling contributes to the development of various pathologies including... Show moreGlucocorticoids regulate numerous processes in human physiology, but deregulated or excessive glucocorticoid receptor (GR) signaling contributes to the development of various pathologies including metabolic syndrome. For this reason, GR antagonists have considerable therapeutic value. Yet, the only GR antagonist that is clinically approved to date - mifepristone - exhibits cross-reactivity with other nuclear steroid receptors like the progesterone receptor. In this study, we set out to identify novel selective GR antagonists by combining rational chemical design with an unbiased in vitro and in vivo screening approach. Using this pipeline, we were able to identify CORT125329 as the compound with the best overall profile from our octahydro series of novel GR antagonists, and demonstrated that CORT125329 does not exhibit cross-reactivity with the progesterone receptor. Further in vivo testing showed beneficial activities of CORT125329 in models for excessive corticosterone exposure and short- and long-term high-fat diet-induced metabolic complications. Upon CORT125329 treatment, most metabolic parameters that deteriorated upon high-fat diet feeding were similarly improved in male and female mice, confirming activity in both sexes. However, some sexually dimorphic effects were observed including male-specific antagonism of GR activity in brown adipose tissue and female-specific lipid lowering activities after short-term CORT125329 treatment. Remarkably, CORT125329 exhibits beneficial metabolic effects despite its lack of GR antagonism in white adipose tissue. Rather, we propose that CORT125329 treatment restores metabolic activity in brown adipose tissue by stimulating lipolysis, mitochondrial activity and thermogenic capacity. In summary, we have identified CORT125329 as a selective GR antagonist with strong beneficial activities in metabolic disease models, paving the way for further clinical investigation. Show less
Background: Major depressive disorder (MDD) is linked to higher cardio-metabolic comorbidity that may in part be due to the low-grade inflammation and poorer metabolic health observed in MDD.... Show moreBackground: Major depressive disorder (MDD) is linked to higher cardio-metabolic comorbidity that may in part be due to the low-grade inflammation and poorer metabolic health observed in MDD. Heterogeneity of MDD is however large, and immune-inflammatory and metabolic dysregulation is present in only part of the MDD cases. We examined the associations of four depression dimensional profilers (atypical energy-related symptom dimension, melancholic symptom dimension, childhood trauma severity, and anxious distress symptom dimension) with immuno-metabolic outcomes, both cross-sectionally and longitudinally.Methods: Three waves covering a 6-year follow-up (>7000 observations) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression profilers were based on the Inventory of Depressive Symptomatology, the Beck Anxiety Inventory, and the Childhood Trauma index. An inflammatory index (based on IL-6 and CRP), a metabolic syndrome index (based on the five metabolic syndrome components), and a combination of these two indices were constructed. Mixed models were used for cross-sectional and longitudinal models, controlling for covariates.Results: Of the four depression profilers, only the atypical, energy-related symptom dimension showed robust associations with higher scores on the inflammatory, metabolic syndrome and combined inflammatory-metabolic indexes cross-sectionally, as well as at follow-up. The melancholic symptom dimension was associated with lower scores on the metabolic syndrome index both cross-sectionally and longitudinally.Conclusion: The atypical energy-related symptom dimension was linked to poorer immune-inflammatory and metabolic health, while the melancholic symptom dimension was linked to relatively better metabolic health. Persons with high atypical energy-related symptom burden, representing an immuno-metabolic depression, may be the most important group to target in prevention programs for cardiometabolic disease, and may benefit most from treatments targeting immuno-metabolic pathways. Show less
Sigit, F.S.; Tahapary, D.L.; Trompet, S.; Sartono, E.; Dijk, K.W. van; Rosendaal, F.R.; Mutsert, R. de 2020
Background The prevalence of metabolic syndrome varies among populations with different ethnicities. Asian populations develop metabolic complications at lower amounts of adiposity than western... Show moreBackground The prevalence of metabolic syndrome varies among populations with different ethnicities. Asian populations develop metabolic complications at lower amounts of adiposity than western populations. The role of abdominal obesity in the metabolic differences between the two populations is poorly understood. Objectives Our objectives were to estimate the prevalence of metabolic syndrome and the relative contribution of its components in the Indonesian and the Dutch population, as well as to examine the associations of overall and abdominal obesity with metabolic syndrome. Methods In this cross-sectional study of middle-aged adults in the Netherlands Epidemiology of Obesity Study (n = 6602) and the Indonesian National Health Surveillance (n = 10,575), metabolic syndrome was defined by the unified IDF and AHA/NHLBI criteria. We performed logistic and linear regressions to examine associations of BMI and waist circumference with the metabolic syndrome, mutually adjusted for waist circumference and BMI. Results The prevalence of metabolic syndrome was 28% and 46% in Indonesian men and women, and 36% and 24% in Dutch men and women. The most prominent components were hypertension (61%) and hyperglycemia (51%) in the Indonesian, and hypertension (62%) and abdominal obesity (40%) in the Dutch population. Per SD in BMI and waist circumference, odds ratios (ORs, 95% CI) of metabolic syndrome were 1.5 (1.3-1.8) and 2.3 (1.9-2.7) in Indonesian men and 1.7 (1.2-2.5) and 2.9 (2.1-4.1) in Dutch men. The ORs of metabolic syndrome were 1.4 (1.2-1.6) and 2.3 (2.0-2.7) in Indonesian women and 1.0 (0.8-1.3) and 4.2 (3.2-5.4) in Dutch women. Conclusion More Indonesian women than men have metabolic syndrome, whereas the opposite is true for the Dutch population. In both the Indonesian and the Dutch populations, hypertension is the primary contributor to the prevalence of metabolic syndrome. In both populations, abdominal adiposity was more strongly associated with metabolic syndrome than overall adiposity. Show less
Veltman, E.M.; Lamers, F.; Comijs, H.C.; Waal, M.W.M. de; Stek, M.L.; Mast, R.C. van der; Rhebergen, D. 2017
