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Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy ( 1 H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1 H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity. Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1 H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.

Body fat distribution is, next to overall obesity, an important risk factor for cardiometabolic outcomes in the general population. In particular, visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Since it is unclear whether body fat distribution is also important in men and women with obesity we investigated the associations between measures of body fat distribution and cardiometabolic risk factors in men and women with obesity. In this cross-sectional analysis of obese men and women (BMI≥30 kg/m2) included in the Netherlands Epidemiology of Obesity Study, waist:hip ratio(WHR), waist circumference, and MRI-based abdominal subcutaneous adipose tissue (aSAT) and VAT were determined. Associations between measures of body fat distribution and presence of ≥1 risk factor, such as hypertension or hypertriglyceridemia, were examined using logistic regression analyses; stratified by sex and adjusted for age, ethnicity, education, tobacco smoking, alcohol consumption, physical activity and depending on the association additionally for total body fat or VAT. We included 2,983 obese individuals (57% women) with a mean age of 56 and standard deviation (SD) of 6 and mean BMI of 34.0 kg/m2 (4.0), after exclusion of individuals with missing values of cardiometabolic risk factors (n = 33). 241 individuals were obese without other cardiometabolic risk factors. In obese women, all measures of body fat distribution except aSAT (OR per SD:0.76, 95%CI: 0.53, 1.10) were associated with having ≥1 cardiometabolic risk factor, of which VAT most strongly associated (5.77; 3.02, 11.01). In obese men, associations of body fat distribution and the presence of cardiometabolic risk factors were attenuated. (e.g. VAT:1.42; 0.84, 2.41). In obese women, but less so in men, measures of body fat distribution, of which VAT most strongly, are associated with cardiometabolic risk factors.

Background 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.

IntroductionTo understand how individuals (self-)manage obesity, insight is needed into how patients perceive their condition and how this perception translates into health outcomes (e.g., health-related quality of life, HRQOL). Our objectives were (1) to examine illness perceptions in individuals with overweight and obesity, and (2) to investigate associations of these perceptions with physical and mental HRQOL.MethodsIn a cross-sectional analysis of the Netherlands Epidemiology of Obesity Study (n = 6432; 52% women), illness perceptions were assessed using the Brief Illness Perception Questionnaire, and HRQOL was assessed using the 36-Item Short-Form Health Survey. Illness perceptions were calculated for different categories of overall, abdominal, and metabolically unhealthy obesity. We investigated associations of illness perceptions with HRQOL using BMI-stratified multivariable linear regression analyses.ResultsCompared to individuals with normal weight, individuals with obesity believed to a higher extent that their condition had more serious consequences [Mean Difference (95%CI): 1.8 (1.6–2.0)], persisted for a longer time [3.4 (3.2–3.6)], manifested in more symptoms [3.8 (3.6–4.0)], caused more worry [4.2 (3.9–4.4)] and emotional distress [2.0 (1.8–2.2)], but was more manageable with medical treatment [3.1 (2.9–3.4)]. They perceived to a lesser extent that they had personal control [−2.2 (−2.4, −2.0)] and understanding [−0.3 (−0.5, −0.1)] regarding their condition. These negative perceptions were less pronounced in individuals with abdominal obesity. Behaviour/Lifestyle was attributed by 73% of participants to be the cause of their obesity. Stronger negative illness perceptions were associated with impaired HRQOL, particularly the physical component.ConclusionIndividuals with obesity perceived their conditions as threatening, and this seemed somewhat stronger in individuals with overall obesity than those with abdominal obesity. Behaviour/Lifestyle is a crucial target intervention and empowering self-management behaviour to achieve a healthy body weight may deliver promising results. In addition, strategies that aim to change negative perceptions of obesity into more adaptive ones may improve HRQOL.

Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to osteopenia or sarcopenia are scarce and inconsistent. To examine the associations of sleep parameters with osteopenia and sarcopenia, considering the influence of sex and menopause. Cross-sectional analysis of 915 participants (45-65 years, 56% women, BMI 26 (range: 18-56) kg/m2) in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. Sleep duration, quality, and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI); bone mineral density and relative appendicular muscle mass were measured by DXA scans. Linear and logistic regressions were performed to associate sleep parameters to bone mineral density, relative appendicular muscle mass, osteopenia (t-score between -1 and -2.5) and sarcopenia (1 SD below average muscle mass). After adjustment for confounding factors, one unit increase in PSQI score (OR and 95% CI, 1.09, 1.03-1.14), declined self-rated sleep quality (1.76, 1.03-3.01), sleep latency (1.18, 1.06-1.31), and a one hour later sleep timing (1.51, 1.08-2.11), but not sleep duration (1.05, 0.90-1.23), were associated with osteopenia. PSQI score (1.10, 1.02-1.19) was also associated with sarcopenia; OR's of sleep latency and later mid-sleep time with sarcopenia were 1.14 (0.99-1.31) and 1.54 (0.91-2.61), respectively. Associations were somewhat stronger in women and varied per menopausal status. These results suggest that decreased sleep quality and a later sleep timing are risk factors for osteopenia and sarcopenia in middle aged individuals.

Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick (\"healthy\") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin (\"risk\") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion.

Clinical epidemiological studies investigate whether an exposure, or risk factor, is causally related to the development or progression of a disease or mortality. It might be of interest to study whether this relation is different in different types of patients. To address such research questions, the presence of interaction among risk factors can be examined. Causal interaction between two risk factors is considered most clinically relevant in epidemiology. Causal interaction occurs when two risk factors act together in causing disease and is explicitly defined as a deviation from additivity on a risk difference scale. Statistical interaction can be evaluated on both an additive (absolute risk) and multiplicative (relative risk) scale, depending on the model that is used. When using logistic regression models, which are multiplicative models, several measures of additive interaction are presented to evaluate whether the magnitude of an association differs across subgroups: the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), or the synergy index (S). For a transparent presentation of interaction effects the recent Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement advises reporting the separate effect of each exposure as well as the joint effect compared with the unexposed group as a joint reference category to permit evaluation of both additive and multiplicative interaction.

AimsTo evaluate whether the association between plasma branched-chain amino acids (BCAA) and intrahepatic lipid (IHL) was affected by physical activity level. Furthermore, to investigate if a conventional exercise training program, a subcategory of physical activity, could lower plasma BCAA along with alterations in IHL content in patients with type 2 diabetes (T2DM) and people with nonalcoholic fatty liver (NAFL).MethodsTo investigate the effect of physical activity on the association between plasma BCAA and IHL content, linear regression analyses were performed in 1983 individuals from the Netherlands Epidemiology of Obesity (NEO) stratified by physical activity frequency. Furthermore, the effect of a 12-week supervised combined aerobic resistance-exercise program on plasma BCAA, insulin sensitivity (hyperinsulinemic–euglycemic clamp), and IHL (proton-magnetic resonance spectroscopy (1H-MRS)) was investigated in seven patients with T2DM, seven individuals with NAFL and seven BMI-matched control participants (CON).ResultsWe observed positive associations between plasma valine, isoleucine and leucine level, and IHL content (1.29 (95% CI: 1.21, 1.38), 1.52 (95% CI: 1.43, 1.61), and 1.54 (95% CI: 1.44, 1.64) times IHL, respectively, per standard deviation of plasma amino acid level). Similar associations were observed in less active versus more active individuals. Exercise training did not change plasma BCAA levels among groups, but reduced IHL content in NAFL (from 11.6 ± 3.0% pre-exercise to 8.1 ± 2.0% post exercise, p < 0.05) and CON (from 2.4 ± 0.6% pre-exercise to 1.6 ± 1.4% post exercise, p < 0.05), and improved peripheral insulin sensitivity in NAFL as well by ~23% (p < 0.05).ConclusionsThe association between plasma BCAA levels and IHL is not affected by physical activity level. Exercise training reduced IHL without affecting plasma BCAA levels in individuals with NAFL and CON. We conclude that exercise training-induced reduction in IHL content is not related to changes in plasma BCAA levels.Trial registrationTrial registry number: NCT01317576.

Background Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. Methods From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45–65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (≥ 130/80 and < 140/90 mmHg; and ≥ 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. Results Normal mean PWV was 6.0 m/s [95% CI 5.8–6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants ≥ 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants ≥ 55 years old in the high blood pressure subgroups. Conclusion This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled trials in adults. Four databases (PubMed, Embase, Web of Science, and COCHRANE Library) were systematically searched for trials with isocaloric diets evaluating the effect of dietary macronutrient composition (energy percentages of fat, carbohydrates, and protein, and their specific types) on liver fat content as assessed by magnetic resonance techniques, computed tomography or liver biopsy. Data on change in liver fat content were pooled by random or fixed-effects meta-analyses and expressed as standardized mean difference (SMD). We included 26 randomized controlled trials providing data for 32 comparisons on dietary macronutrient composition. Replacing dietary fat with carbohydrates did not result in changes in liver fat (12 comparisons, SMD 0.01 (95% CI −0.36; 0.37)). Unsaturated fat as compared with saturated fat reduced liver fat content (4 comparisons, SMD −0.80 (95% CI −1.09; −0.51)). Replacing carbohydrates with protein reduced liver fat content (5 comparisons, SMD −0.33 (95% CI −0.54; −0.12)). Our meta-analyses showed that replacing carbohydrates with total fat on liver fat content was not effective, while replacing carbohydrates with proteins and saturated fat with unsaturated fat was. More well-performed and well-described studies on the effect of types of carbohydrates and proteins on liver fat content are needed, especially studies comparing proteins with fats.