Physical and psychological health at adolescence and home care use later in life

OBJECTIVES: To examine the relation between physical and psychological health indicators at adolescence (age 18) and household, personal, and nursing home care use later in life at ages 57–69 years. METHODS: Using medical examinations on men born in 1944–1947 who were evaluated for military service at age 18 in the Netherlands, we link physical and psychological health assessments to national administrative microdata on the use of home care services at ages 57–69 years. We postulate a panel probit model for home care use over these years. In the analyses, we account for selective survival through correlated panel probit models. RESULTS: Poor mental health and being overweight at age 18 are important predictors of later life home care use. Home care use at ages 57–69 years is also highly related to and interacts with father’s socioeconomic status and recruits’ education at age 18. DISCUSSION: Specific health characteristics identified at age 18 are highly related to the later utilization of home-care at age 57–69 years. Some characteristics may be amenable to early life health interventions to decrease the future costs of long-term home care

Impact of disease screening on awareness and management of hypertension and diabetes between 2011 and 2015: results from the China health and retirement longitudinal study

Background There has been a limited recognition of hypertension and diabetes in China which has compromised optimal treatment. It is not clear if a screening program implemented by a national health survey has improved awareness and management of these conditions. Methods The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing longitudinal health survey conducted since 2011 among Chinese people aged 45 years and older. Participants have been assessed every two years by interviews, physical examinations, and fasting glucose samples were taken in 2011. In 2013 and 2015, participants were asked about awareness and management of selected chronic diseases, and they first became aware of these conditions. Results Of the 11,000+ participants screened in 2011, 4594 were identified with hypertension and 1703 with diabetes by medical examinations. Over 80% of the middle-aged and elderly Chinese diagnosed with hypertension and/or diabetes in 2011 reported in 2015 that they were unaware of the disease(s). Although some improvement was observed between 2011 and 2015, the main reason for the increase in awareness was a medical examination initiated by the study participant (over 75%), by their work unit or community (12–15%), and rarely (less than 3%) by the CHARLS examination. Participants with a rural household registration status and lower BMI were the most likely to be unaware and to remain unaware of their condition(s). Conclusions Disease screening in CHARLS did not lead to significant improvements in awareness of hypertension and diabetes. Improvements should be made by the systematic feedback of screening results to survey participants and the monitoring of disease awareness over time. This will be essential to improve disease recognition and facilitate optimal management

Gains in Life Expectancy Associated with Higher Education in Men

Background: Many studies show large differences in life expectancy across the range of education, intelligence, and socio-economic status. As educational attainment, intelligence, and socio-economic status are highly interrelated, appropriate methods are required to disentangle their separate effects. The aim of this paper is to present a novel method to estimate gains in life expectancy specifically associated with increased education. Our analysis is based on a structural model in which education level, IQ at age 18 and mortality all depend on (latent) intelligence. The model allows for (selective) educational choices based on observed factors and on an unobserved factor capturing intelligence. Our estimates are based on information from health examinations of military conscripts born in 1944–1947 in The Netherlands and their vital status through age 66 (n = 39,798). Results: Our empirical results show that men with higher education have lower mortality. Using structural models to account for education choice, the estimated gain in life expectancy for men moving up one educational level ranges from 0.3 to 2 years. The estimated gain in months alive over the observational period ranges from -1.2 to 5.7 months. The selection effect is positive and amounts to a gain of one to two months. Decomposition of the selection effect shows that the gain from selection on (latent) intelligence is larger than the gain from selection on observed factors and amounts to 1.0 to 1.7 additional months alive. Conclusion: Our findings confirm the strong selection into education based on socio-economic status and intelligence. They also show significant higher life expectancy among individuals with higher education after the selectivity of education choice has been taken into account. Based on these estimates, it is plausible therefore that increases in education could lead to increases in life expectancy

War- and famine-related excess mortality among civilians in the Netherlands, 1944-1945

National estimates exist for war- and famine-related deaths in the Netherlands during the last stages of World War II, but no such estimates are available at the local level. To fill this information gap, this article aims at mapping and visualizing the timing of war- and famine-related excess mortality by municipality among the civilian population within the Netherlands. We use mortality statistics at the level of municipalities because these are the smallest administrative units for which this information is available. We use a seasonally adjusted mortality model combined with a difference-in-difference approach to estimate the number of excess deaths in the period between January 1944 and July 1945 separately for each Dutch municipality

How Much Schizophrenia Do Famines Cause?

Since the 1970s, famines have been widely invoked as natural experiments in research into the long-term impact of foetal exposure to nutritional shocks. That research has produced compelling evidence for a robust link between foetal exposure and the odds of developing schizophrenia. However, the implications of that research for the human cost of famines in the longer run has not been investigated. We address the connection between foetal origins and schizophrenia with that question in mind. The impact turns out to be very modest – much less than one per cent of the associated famine death tolls – across a selection of case studies

DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation

DNA methylation differences after exposure to prenatal famine are common and timing

Prenatal famine in humans has been associated with various later-life consequences, depending on the gestational timing of the insult and the sex of the exposed individual. Epigenetic mechanisms have been proposed to underlie these associations. Indeed, animal studies and our early human data on the imprinted IGF2 locus indicated a link between prenatal nutritional and DNA methylation. However, it remains unclear how common changes in DNA methylation are and whether they are sex-and timing-specific paralleling the later-life consequences of prenatal famine exposure. To this end, we investigated the methylation of 15 loci implicated in growth and metabolic disease in individuals who were prenatally exposed to a war-time famine in 1944-45. Methylation of INSIGF was lower among individuals who were periconceptionally exposed to the famine (n 5 60) compared with their unexposed same-sex siblings (P 5 2 3 10 25 ), whereas methylation of IL10, LEP, ABCA1, GNASAS and MEG3 was higher (all P < 10 23 ). A significant interaction with sex was observed for INSIGF, LEP and GNASAS. Next, methylation of eight representative loci was compared between 62 individuals exposed late in gestation and their unexposed siblings. Methylation was different for GNASAS (P 5 1.1 3 10 27 ) and, in men, LEP (P 5 0.017). Our data indicate that persistent changes in DNA methylation may be a common consequence of prenatal famine exposure and that these changes depend on the sex of the exposed individual and the gestational timing of the exposure

DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342, 596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formalmediation analysis.DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing b cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-termmetabolic health. The specific mechanism awaits elucidation.</p

Prenatal Famine and Genetic Variation Are Independently and Additively Associated with DNA Methylation at Regulatory Loci within IGF2/H19

Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944–45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (PBH<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (PBH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (PBH = 3.4×10−3). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site