Epidemiological evidence is accumulating that indicates greater time spent in sedentary behavior is associated with all-cause and cardiovascular morbidity and mortality in adults such that some ...countries have disseminated broad guidelines that recommend minimizing sedentary behaviors. Research examining the possible deleterious consequences of excess sedentary behavior is rapidly evolving, with the epidemiology-based literature ahead of potential biological mechanisms that might explain the observed associations. This American Heart Association science advisory reviews the current evidence on sedentary behavior in terms of assessment methods, population prevalence, determinants, associations with cardiovascular disease incidence and mortality, potential underlying mechanisms, and interventions. Recommendations for future research on this emerging cardiovascular health topic are included. Further evidence is required to better inform public health interventions and future quantitative guidelines on sedentary behavior and cardiovascular health outcomes.
Current guidelines published by the American Heart Association and the American College of Cardiology broadly recommend lifestyle approaches to prevent and treat elevated blood pressure and ...cholesterol. For patients with mildly or moderately elevated blood pressure and blood cholesterol, lifestyle-only approaches are the first line of therapy. The purpose of this scientific statement is to: (1) highlight the mild-moderate-risk patient groups indicated for lifestyle-only treatment for elevated blood pressure or cholesterol; (2) describe recommendations, average effects, and additional considerations when prescribing lifestyle treatment with physical activity; and (3) provide guidance and resources for clinicians to assess, prescribe, counsel, and refer to support increased physical activity in their patients. An estimated 21% and 28% to 37% of US adults, respectively, have mild-moderate-risk blood pressure and cholesterol and should receive lifestyle-only as first-line treatment. Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes. Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol.
The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of ...this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
Abstract
Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine ...(CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010–2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): −305.5, −44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P < 6.94 × 10−8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: −543, −86) among smokers but no mediated effect for nonsmokers (β = −38 g; 95% CI: −88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight.
It is now well accepted that offspring exposed to maternal undernutrition, obesity, or gestational diabetes mellitus have an increased risk for chronic diseases later in life, supporting the theory ...of the early origins of chronic diseases. However, the molecular mechanisms through which the exposure to an altered in utero environment translates into the development of chronic diseases are not yet well understood. Recently reported promising results help to resolve this issue. They suggest that epigenetic modifications are a potential mechanism for fetal metabolic programming. This review provides an overview of the relationship between the exposure to an altered intrauterine environment and fetal metabolic programming, focusing on gestational diabetes mellitus and epigenetic variations at adipokine candidate genes.
The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as ‘diabetes’. Increased knowledge of ...this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment) and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e. monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realise its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
Summary
Background
Childhood obesity has been associated with prenatal exposure to maternal hyperglycaemia, but we lack understanding about maternal insulin physiologic components that contribute to ...this association.
Objectives
Evaluate the association between maternal insulin sensitivity during pregnancy and adiposity measures in childhood.
Methods
In 422 mother–child pairs, we tested associations between maternal insulin sensitivity measures at ~26 weeks of pregnancy and child adiposity measures, including dual‐energy X‐ray absorptiometry body composition and anthropometry (body mass index and waist circumference) at ~5 years. We used linear regression analyses to adjust for maternal age, ethnicity, gravidity, first‐trimester body mass index, and child sex and age at mid‐childhood.
Results
In early pregnancy, maternal mean age was 28.6 ± 4.3 years and median body mass index was 24.1 kg/m2. Lower maternal insulin sensitivity indices were correlated with greater child adiposity based on anthropometry measures and on dual‐energy X‐ray absorptiometry total and trunk % fat in univariate associations (r = −0.122 to −0.159). Lower maternal insulin sensitivity was specifically associated with higher dual‐energy X‐ray absorptiometry trunk % fat (n = 359 for Matsuda; β = −0.034 ± 0.013; p = 0.01) after adjustment for covariates, including maternal body mass index.
Conclusions
Maternal insulin sensitivity during pregnancy may contribute to increased risk for higher offspring central adiposity in middle childhood.
Background
Over‐the‐counter analgesics during pregnancy or infancy may be related to neurobehavioural problems in children, but little is known about effects of different analgesic types, dosage, and ...timing.
Objectives
Examine associations of acetaminophen and ibuprofen use during pregnancy and infancy with executive function and behaviour problems in children.
Methods
We included 1225 mother‐child pairs from Project Viva, a pre‐birth cohort study. We assessed prenatal acetaminophen and ibuprofen use in early and mid‐pregnancy and infant use in the first year of life using questionnaires. Parents and classroom teachers assessed child behaviours in mid‐childhood (median 8 years), using the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both. We examined associations of acetaminophen and ibuprofen use during pregnancy and infancy with mid‐childhood neurobehavioural outcomes using linear regression models adjusted for potential confounders.
Results
During pregnancy, 46.1% of mothers used acetaminophen ≥10 times and 18.4% used any ibuprofen. In the first year, 65.3% and 39.6% of infants received acetaminophen and ibuprofen ≥6 times, respectively. Higher (≥10 vs <10 times) prenatal acetaminophen (β 1.64 points; 95% confidence interval CI 0.59, 2.68) and any ibuprofen (β 1.56, 95% CI 0.19, 2.92) were associated with higher parent‐rated BRIEF global scores. Patterns of association were linear across categories and were similar for other parent‐ and teacher‐rated outcomes. Infancy exposure (≥6 vs <6 times) to acetaminophen (β 1.69, 95% CI 0.51, 2.87) and ibuprofen (β 1.40, 95% CI 0.25, 2.55) were associated with higher parent‐rated BRIEF GEC scores but associations with teacher‐rated scores were weaker.
Conclusions
Prenatal and early‐life exposure to acetaminophen and ibuprofen were associated with poorer executive function and behaviour in childhood. These findings highlight the need for further research on the mechanisms through which analgesics may act on fetal and child brain development.
Several per- and polyfluoroalkyl substances (PFAS) are ubiquitous anthropogenic pollutants almost universally detected in humans. Experimental evidence indicates that PFAS alter glucose metabolism ...and insulin secretion. However, epidemiological studies have yielded inconsistent results.
We sought to examine associations between plasma PFAS concentrations, glycemic indicators, and diabetes incidence among high-risk adults.
Within the Diabetes Prevention Program (DPP), a trial for the prevention of type 2 diabetes among high-risk individuals, we quantified baseline plasma concentrations of nine PFAS among 957 participants randomized to a lifestyle intervention or placebo. We evaluated adjusted associations for plasma PFAS concentrations with diabetes incidence and key glycemic indicators measured at baseline and annually over up to 4.6 y.
Plasma PFAS concentrations were similar to those reported in the U.S. population in 1999-2000. At baseline, in cross-sectional analysis, a doubling in plasma perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) concentrations was associated with higher homeostatic model assessment of insulin resistance (HOMA-IR) β
=0.39; 95% confidence interval (CI): 0.13, 0.66; β
=0.64; 95% CI: 0.34, 0.94, β-cell function (HOMA-β) (β
=9.62; 95% CI: 1.55, 17.70; β
=15.93; 95% CI: 6.78, 25.08), fasting proinsulin (β
=1.37 pM; 95% CI: 0.50, 2.25; β
=1.71 pM; 95% CI: 0.72, 2.71), and glycated hemoglobin (HbA
) (β
=0.03%; 95% CI: 0.002, 0.07; β
=0.04%; 95% CI: 0.001, 0.07). There was no strong evidence of associations between plasma PFAS concentrations and diabetes incidence or prospective changes in glycemic indicators during the follow-up period.
At baseline, several PFAS were cross-sectionally associated with small differences in markers of insulin secretion and β-cell function. However, there was limited evidence suggesting that PFAS concentrations are associated with diabetes incidence or changes in glycemic indicators during the follow-up period. https://doi.org/10.1289/EHP1612.
The Child Opportunity Index (ChOI) is a publicly available surveillance tool that incorporates traditional and novel attributes of neighborhood conditions that may promote or inhibit healthy child ...development. The extent to which ChOI relates to individual-level cardiometabolic risk remains unclear.
We geocoded residential addresses obtained from 743 participants in midchildhood (mean age 7.9 years) in Project Viva, a prebirth cohort from eastern Massachusetts, and linked each location with census tract-level ChOI data. We measured adiposity and cardiometabolic outcomes in midchildhood and early adolescence (mean age 13.1 years) and analyzed their associations with neighborhood-level ChOI in midchildhood using mixed-effects models, adjusting for individual and family sociodemographics.
On the basis of nationwide distributions of ChOI, 11.2% (
= 83) of children resided in areas of very low overall opportunity (ChOI score <20 U) and 55.3% (
= 411) resided in areas of very high (ChOI score ≥80 U) overall opportunity. Children who resided in areas with higher overall opportunity in midchildhood had persistently lower levels of C-reactive protein from midchildhood to early adolescence (per 25-U increase in ChOI score: β = .14 mg/L; 95% confidence interval, .28 to .00). Additionally, certain ChOI indicators, such as greater number of high-quality childhood education centers, greater access to healthy food, and greater proximity to employment in midchildhood, were associated with persistently lower adiposity, C-reactive protein levels, insulin resistance, and metabolic risk
scores from midchildhood to early adolescence.
Our findings suggest more favorable neighborhood opportunities in midchildhood predict better cardiometabolic health from midchildhood to early adolescence.
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