The prevailing interpretation of the global epidemic of obesity is that it is a consequence of changes in societies toward more so-called obesogenic environments, changes which involve the emergence of living conditions that promote persisting positive energy balance. A critical implication of this contention is that the development of the epidemic has followed the corresponding development of the obesogenic environment. This chapter focuses on the history of the obesity epidemic in Danish children and young adult men since the interwar period. Surprisingly, the epidemic has developed in sharply delineated phases closely linked to year of birth, a pattern that is not concordant with the presumed obesogenic changes, which are also problematic for other theoretical and empirical reasons. These findings suggest that the drivers of the epidemic are some changes in the perinatal environment, perhaps even before conception, increasing risk of obesity later in life. Identification of these drivers of the epidemic may offer strong preventive tools to combat obesity.
Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother and child.From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level.
Objective: To assess the effectiveness of β-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. Data Sources: Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. Study Selection: Randomized trials comparing β-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of β-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of β-blockers and 15 of sclerotherapy were published as full papers. Data Extraction: Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. Data Synthesis: The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of β-blockers was significantly reduced (pooled odds ratio, 0.54; 95% Cl, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; Cl, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; Cl, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. Conclusions: Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.
Additional file 1. Table S1: “Summary of the studies in the meta-analysis for the association between Season of Birth and DNA methylation at birth and in children (age: 1 to 11 years)”. Baseline summary of participants from each of the individual cohorts.
Background Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. Methodology/Principal Findings The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50–64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. Conclusions/Significance Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years.
Abstract We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a 2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c 2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a 2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a 2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c 2 = 0.31; 0.29–0.33 and c 2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
<p> </p> <p><strong>Objective</strong></p> <p>The association between <em>FTO</em> rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, if PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms.</p> <p><strong>Research Design and Methods</strong></p> <p>Genetic association analyses comprised up to 19,585 individuals. PA was self-reported and IS was defined based on inverted HOMA-IR. Functional analyses were performed in muscle biopsies from 140 men, and in cultured muscle cells.</p> <p><strong>Results</strong></p> <p>The BMI-increasing effect of the <em>FTO</em> rs9939609 A-allele was attenuated by 47% with high PA (β (standard error (SE)), -0.32 (0.10) kg/m2, p=0.0013), and by 51% with high IS (-0.31 (0.09) kg/m2, p=0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 (0.09) kg/m2, p=0.023; IS, -0.28 (0.09) kg/m2, p=0.0011). The rs9939609 A-allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, p>0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A-allele was associated with higher expression of <em>FTO </em>in skeletal muscle tissue (0.03 (0.01), p=0.011), and in skeletal muscle cells, we identified a physical interaction between the <em>FTO</em> promoter and an enhancer region encompassing rs9939609. </p> <p><strong>Conclusions </strong></p> <p>Greater PA and IS independently reduced the effect of rs9939609 on obesity. These effects might be mediated through altered expression of <em>FTO</em> in skeletal muscle. Our results indicated that PA and/or other means of increasing insulin sensitivity could counteract <em>FTO</em>–related genetic predisposition to obesity.</p>
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