Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta-Analysis of 19 005 Individuals.

SCOPE: Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL-1ß inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may alter T2D risk factors. METHODS: Meta-analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3-related single-nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance. RESULTS: SFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL-1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (ß ± SE = -0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL-1 , per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression. CONCLUSION: Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants.

Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals.

BACKGROUND: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans. OBJECTIVE: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes. METHODS: A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes. RESULTS: The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs. CONCLUSIONS: We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

Protein intake and the incidence of pre-diabetes and diabetes in 4 population-based studies: the PREVIEW project.

BACKGROUND: Data on the relationship between protein intake and the risk of type 2 diabetes are conflicting. OBJECTIVE: We studied prospective associations between the intake of total, plant-based, and animal protein and the risk of pre-diabetes and diabetes in 4 population-based studies included in the PREVIEW project. METHODS: Analyses were conducted with the use of data from 3 European cohorts and 1 Canadian cohort, including 78,851 participants. Protein intake was assessed through the use of harmonized data from food-frequency questionnaires or 3-d dietary records. Cohort-specific incidence ratios (IRs) were estimated for pre-diabetes and diabetes, adjusting for general characteristics, lifestyle and dietary factors, disease history, and body mass index (BMI) and waist circumference; results were pooled based on a random-effects meta-analysis. RESULTS: Higher total protein intake (g · kg-1 · d-1) was associated with lower incidences of pre-diabetes and diabetes (pooled IRs: 0.84; 95% CI: 0.82, 0.87 and 0.49; 95% CI: 0.28, 0.83, respectively); plant-based protein intake was the main determinant (pooled IRs: 0.83; 95% CI: 0.81, 0.86 and 0.53; 95% CI: 0.36, 0.76, respectively). Substituting 2 energy percentage (E%) protein at the expense of carbohydrates revealed increased risks of pre-diabetes and diabetes (pooled IRs: 1.04; 95% CI: 1.01, 1.07 and 1.09; 95% CI: 1.01, 1.18, respectively). Except for the associations between intakes of total protein and plant-based protein (g · kg-1 · d-1) and diabetes, all other associations became nonsignificant after adjustment for BMI and waist circumference. CONCLUSIONS: Higher protein intake (g · kg-1 · d-1) was associated with a lower risk of pre-diabetes and diabetes. Associations were substantially attenuated after adjustments for BMI and waist circumference, which demonstrates a crucial role for adiposity and may account for previous conflicting findings. This study was registered at ISRCTN as ISRCTN31174892.

Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies.

Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations - the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 ± 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 ± 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.

Outdoor time and dietary patterns in children around the world.

Background: Whether outdoor time is linked to dietary patterns of children has yet to be empirically tested. The objective of this study was to examine the association between outdoor time and dietary patterns of children from 12 countries around the world. Methods: This multinational, cross-sectional study included 6229 children 9-11 years of age. Children self-reported the time that they spent outside before school, after school and on weekends. A composite score was calculated to reflect overall daily outdoor time. Dietary patterns were assessed using a food frequency questionnaire, and two components were used for analysis: healthy and unhealthy dietary pattern scores. Results: On average, children spent 2.5 h outside per day. After adjusting for age, sex, parental education, moderate-to-vigorous physical activity, screen time and body mass index z-score, greater time spent outdoors was associated with healthier dietary pattern scores. No association was found between outdoor time and unhealthy dietary pattern scores. Similar associations between outdoor time and dietary patterns were observed for boys and girls and across study sites. Conclusions: Greater time spent outside was associated with a healthier dietary pattern in this international sample of children. Future research should aim to elucidate the mechanisms behind this association.

Higher step count is associated with greater bone mass and strength in women but not in men.

In this cross-sectional study, peripheral bone traits were examined relative to total daily steps measured with pedometer. Higher number of steps was associated with greater bone values at the calcaneus and tibia in women, but not in men. In women, dose-dependent associations at the radius were congruent with the weight-bearing bones. INTRODUCTION: Habitual physical activity measured as daily steps may contribute to bone density and strength at the calcaneus and other weight-bearing bones. METHODS: Subgroups of 705-837 women and 480-615 men aged 31-46 years from the Cardiovascular Risk in Young Finns Study participated in the present study. Participants were instructed to use pedometer for 1 week, and the total daily steps, divided into tertiles, were evaluated relative to quantitative ultrasound-measured bone traits at the calcaneus and peripheral quantitative computed tomography-measured bone traits at the tibia and radius. Analysis of covariance was used to examine the between-group differences. RESULTS: In women, significant dose-dependent between-group differences were found in the weight-bearing bones and in non-weight-bearing radius. The differences in broadband ultrasound attenuation and speed of sound at the calcaneus were 3.8 and 0.5% greater in women within the highest tertile of daily steps compared to the lowest tertile (p values for trend ≤ 0.04). In tibia, women in the highest tertile (> 8765 steps/day) had on average 1-5.4% greater bone cross-sectional area, bone mineral content (BMC), trabecular density, and bone strength index at the distal site and 1.6-2.7% greater bone areas, BMC and strength strain index (SSI) at the shaft compared to women with less daily steps (p values for trend ≤ 0.02). Similarly, in radius, BMC and BSI at the distal site, and bone cross-sectional areas, BMC and SSI at the shaft were 1.7-3.4% greater in women within the highest tertile of daily steps compared to their peers (p values for trend ≤ 0.04). In men, the differences in calcaneal, tibial, and radial bone traits were mainly non-significant between the tertiles of daily steps. CONCLUSION: Observed significant positive associations between daily steps and various bone traits at the calcaneus, tibia, and radius in women suggest that habitual physical activity may benefit skeletal health in adulthood.

Dietary patterns and their associations with home food availability among Finnish pre-school children: a cross-sectional study.

OBJECTIVE: To study the associations between home food availability and dietary patterns among pre-school children. DESIGN: Cross-sectional study in which parents of the participating children filled in an FFQ and reported how often they had certain foods in their homes. We derived dietary pattern scores using principal component analysis, and composite scores describing the availability of fruits and vegetables as well as sugar-enriched foods in the home were created for each participant. We used multilevel models to investigate the associations between availability and dietary pattern scores. SETTING: The DAGIS study, Finland. SUBJECTS: The participants were 864 Finnish 3-6-year-old children recruited from sixty-six pre-schools. The analyses included 711 children with sufficient data. RESULTS: We identified three dietary patterns explaining 16·7 % of the variance. The patterns were named 'sweets-and-treats' (high loadings of e.g. sweet biscuits, chocolate, ice cream), 'health-conscious' (high loadings of e.g. nuts, natural yoghurt, berries) and 'vegetables-and-processed meats' (high loadings of e.g. vegetables, cold cuts, fruit). In multivariate models, the availability of fruits and vegetables was inversely associated with the sweets-and-treats pattern (ß=-0·05, P<0·01) and positively associated with the health-conscious (ß=0·07, P<0·01) and vegetables-and-processed meats patterns (ß=0·06, P<0·01). The availability of sugar-enriched foods was positively associated with the sweets-and-treats pattern (ß=0·10, P<0·01) and inversely associated with the health-conscious pattern (ß=-0·03, P<0·01). CONCLUSIONS: Considering dietary patterns, the availability of sugar-enriched foods in the home seems to have a stronger role than that of fruits and vegetables. Parents should restrict the availability of unhealthy foods in the home.

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

SCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. METHODS AND RESULTS: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10-8) such that each serving of low-fat dairy was associated with 0.225 kg m-2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. CONCLUSION: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis.

AIMS/HYPOTHESIS: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. METHODS: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. RESULTS: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (ß ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10-3) and higher fasting insulin (0.030 ± 0.005 [log e pmol/l], p = 2.0 × 10-10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the ß-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 log e pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. CONCLUSIONS/INTERPRETATION: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis. TRIAL REGISTRATION: Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses' Health Study).

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR-The PREVIEW Project.

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires (n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope -0.02 ± 0.01 mmol/mol, p < 0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 ± 0.02 mL/min/1.73 m², p < 0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score.

Socioeconomic status and dietary patterns in children from around the world: different associations by levels of country human development?

BACKGROUND: Although 'unhealthy' diet is a well-known risk factor for non-communicable diseases, its relationship with socio-economic status (SES) has not been fully investigated. Moreover, the available research has largely been conducted in countries at high levels of human development. This is the first study to examine relationships among dietary patterns and SES of children from countries spanning a wide range of human development. METHODS: This was a multinational cross-sectional study among 9-11 year-old children (n = 6808) from urban/peri-urban sites across 12 countries. Self-reported food frequency questionnaires were used to determine the children's dietary patterns. Principal Components Analysis was employed to create two component scores representing 'unhealthy' and 'healthy' dietary patterns. Multilevel models accounting for clustering at the school and site level were used to examine the relationships among dietary patterns and SES. RESULTS: The mean age of participants in this study (53.7% girls) was 10.4 years. Largest proportions of total variance in dietary patterns occurred at the individual, site, and school levels (individual, school, site: 62.8%; 10.8%; 26.4% for unhealthy diet pattern (UDP) and 88.9%; 3.7%; 7.4%) for healthy diet pattern (HDP) respectively. There were significant negative 'unhealthy' diet-SES gradients in 7 countries and positive 'healthy' diet-SES gradients in 5. Within country diet-SES gradients did not significantly differ by HDI. Compared to participants in the highest SES groups, unhealthy diet pattern scores were significantly higher among those in the lowest within-country SES groups in 8 countries: odds ratios for Australia (2.69; 95% CI: 1.33-5.42), Canada (4.09; 95% CI: 2.02-8.27), Finland (2.82; 95% CI: 1.27-6.22), USA (4.31; 95% CI: 2.20-8.45), Portugal (2.09; 95% CI: 1.06-4.11), South Africa (2.77; 95% CI: 1.22-6.28), India (1.88; 95% CI: 1.12-3.15) and Kenya (3.35; 95% CI: 1.91-5.87). CONCLUSIONS: This study provides evidence of diet-SES gradients across all levels of human development and that lower within-country SES is strongly related to unhealthy dietary patterns. Consistency in within-country diet-SES gradients suggest that interventions and public health strategies aimed at improving dietary patterns among children may be similarly employed globally. However, future studies should seek to replicate these findings in more representative samples extended to more rural representation.

Positive Psychosocial Factors in Childhood Predicting Lower Risk for Adult Type 2 Diabetes: The Cardiovascular Risk in Young Finns Study, 1980-2012.

INTRODUCTION: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. METHODS: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. RESULTS: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI=0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b= -0.01; p=0.010) for participants with higher versus lower positive psychosocial score in childhood. CONCLUSIONS: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted.

Psychosocial environment in childhood and body mass index growth over 32years.

The psychosocial environment and especially various psychosocial risks in childhood have been shown to predict later negative health behavior and health problems. In this study, we examined whether various psychosocial factor domains in childhood and adolescence: socioeconomic status, the emotional family environment (parental nurturance, life-satisfaction), parental lifestyle, life-events, the child's self-regulatory behavior and the child's social adaptation were associated with body mass index (BMI) trajectories individually by domain and as a cumulative score across domains. The participants were a nationally representative sample of 2016 men and women from the Young Finns study aged 3-18years at study entry in 1980. Their BMI was measured at six study phases from 1980 to 2012. Their parents reported all the factors related to their psychosocial environment in 1980. The participants responded to questions on adulthood socioeconomic status in 2007. The accumulation of psychosocial factors in childhood was the main exposure variable. The findings from repeated measures multilevel modeling showed that parental lifestyle and life-events and the more positive cumulative psychosocial factors score were associated with a slower increase in BMI during follow-up (regression coefficient range from -0.06 to -0.50). In conclusion, the psychosocial environment in childhood and adolescence, particularly parental lifestyle and lack of stressful life-events, are associated with a lower increase of BMI.

Ideal cardiovascular health in childhood-Longitudinal associations with cardiac structure and function: The Special Turku Coronary Risk Factor Intervention Project (STRIP) and the Cardiovascular Risk in Young Finns Study (YFS).

BACKGROUND: Ideal cardiovascular health (CVH), defined by the American Heart Association, is associated with incident cardiovascular disease in adults. However, association of the ideal CVH in childhood with current and future cardiac structure and function has not been studied. METHODS AND RESULTS: The sample comprised 827 children participating in the longitudinal Special Turku Coronary Risk Factor Intervention Project (STRIP) and The Cardiovascular Risk in Young Finns Study (YFS). In STRIP, complete data on the seven ideal CVH metrics and left ventricular (LV) mass measured with echocardiography were available at the age of 15 (n=321), 17 (n=309) and 19 (n=283) years. In YFS, the cohort comprised children aged 12-18years (n=506) with complete ideal CVH metrics data from childhood and 25years later in adulthood, and echocardiography performed in adulthood. In STRIP, ideal CVH score was inversely associated with LV mass during childhood (P=0.036). In YFS, childhood ideal CVH score was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume in adulthood (all P<0.01). In addition, improvement of the ideal CVH score between childhood and adulthood was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume (all P≤0.03). CONCLUSIONS: Childhood ideal CVH score has a long-lasting effect on cardiac structure and function, and the association is evident already in childhood. Our findings support targeting the ideal CVH metrics as part of primordial prevention of cardiovascular diseases.

Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study.

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. CONCLUSION: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).

Intergenerational transmission of socioeconomic position and ideal cardiovascular health: 32-year follow-up study.

OBJECTIVES: Socioeconomic position (SEP) in childhood predicts cardiovascular health in adulthood but the underlying mechanisms remain unclear. Using a longitudinal study design, we examined the extent to which adult SEP acts as a pathway (mediator) connecting childhood SEP with adult cardiovascular health, and if upward social mobility mitigates the health-effects of early low SEP. METHOD: The sample comprised 697 participants from a prospective Finnish cohort followed during 32 years. Childhood SEP was assessed from the parents in 1980 (participant mean age 10.9) and adulthood SEP was examined in 2007 and 2012 (participant mean age 43.2 in 2012). Both childhood and adulthood SEP scores comprised education, income, occupational status, and occupational stability. Ideal cardiovascular health was assessed in 2007 and 2012 according to the American Heart Association's guidelines. RESULTS: Higher childhood SEP was associated with higher ideal cardiovascular health index in adulthood (ß = 0.13, p < .001) independently of sex, age, childhood cardiovascular risk factors, and chronic conditions. Mediation analysis showed that adult SEP accounted for 33% of the association between childhood SEP and ideal cardiovascular health index. Upwardly mobile participants scored higher on ideal cardiovascular health in adulthood compared with participants staying in lower SEP (M = 4.05 vs. 3.56, p < .001). CONCLUSIONS: Transmission of SEP over generations is a predictor of health inequalities, which should be considered in cardiovascular prevention. Although upward social mobility mitigates some of the effect of early SEP disadvantage on later cardiovascular health, childhood SEP remains an important predictor of future health. (PsycINFO Database Record

Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study.

BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.

East-west differences and migration in Finland: Association with cardiometabolic risk markers and IMT. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Coronary heart disease mortality has been internationally high in eastern Finland. The excessive mortality risk in Eastern compared with western Finns is explained by differences in cardiometabolic risk profile. Current risk profile differences and association with migration have not been reported. We examined the association of place of residence (east-west) and specifically migration with cardiometabolic risk markers and carotid intima-media thickness (IMT). METHODS: The study population included 2204 participants with data available from childhood/youth in 1980 and follow-up examination in 2007. RESULTS: Participants residing in eastern Finland in adulthood had 0.022±0.004mm higher IMT than Western participants. Those who migrated east-to-west had lower IMT than those staying in the east (0.027±0.006mm, p<0.0001) while no difference to those continuously living in the west was found. Those who moved east-to-west had a lower body mass index (25.3±4.3 kg/m(2) vs. 26.2±4.5kg/m(2), p=0.01), waist circumference (85.7±12.8cm vs. 88.6±12.8cm, p=0.001), prevalence of metabolic syndrome (13% vs. 21%, p=0.01), and higher socioeconomic status (16.6±3.3 vs. 15.0±3.3 school years, p<0.0001) than those who stayed in the east. CONCLUSIONS HIGHER IMT WAS FOUND IN EASTERN FINNS THAN IN WESTERN FINNS PARTICIPANTS WHO MIGRATED EAST-TO-WEST HAD A LOWER IMT AND A BETTER CARDIOMETABOLIC RISK PROFILE THAN THOSE WHO STAYED IN THE EAST.