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).

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).

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.

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.

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

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.

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.

Cumulative effect of psychosocial factors in youth on ideal cardiovascular health in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: The American Heart Association has defined a new metric of ideal cardiovascular health as part of its 2020 Impact Goals. We examined whether psychosocial factors in youth predict ideal cardiovascular health in adulthood. METHODS AND RESULTS: Participants were 477 men and 612 women from the nationwide Cardiovascular Risk in Young Finns Study. Psychosocial factors were measured from cohorts 3 to 18 years of age at the baseline of the study, and ideal cardiovascular health was examined 27 years later in adulthood. The summary measure of psychosocial factors in youth comprised socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. There was a positive association between a higher number of favorable psychosocial factors in youth and greater ideal cardiovascular health index in adulthood (ß=0.16; P<0.001) that persisted after adjustment for age, sex, medication use, and cardiovascular risk factors in childhood (ß=0.15; P<0.001). The association was monotonic, suggesting that each increment in favorable psychosocial factors was associated with improvement in cardiovascular health. Of the specific psychosocial factors, a favorable socioeconomic environment (ß=0.12; P<0.001) and participants' self-regulatory behavior (ß=0.07; P=0.004) were the strongest predictors of ideal cardiovascular health in adulthood. CONCLUSIONS: The findings suggest a dose-response association between favorable psychosocial factors in youth and cardiovascular health in adulthood, as defined by the American Heart Association metrics. The effect seems to persist throughout the range of cardiovascular health, potentially shifting the population distribution of cardiovascular health rather than simply having effects in a high-risk population.

Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

BACKGROUND: High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. METHODS AND RESULTS: We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P=4×10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6×10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5×10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). CONCLUSIONS: Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.

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.

Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site.

Genome-wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its potential for functionality. The rs13702 minor allele had been predicted to disrupt a microRNA (miR) recognition element (MRE) seed site (MRESS) for the human microRNA-410 (miR-410). Furthermore, rs13702 is in linkage disequilibrium (LD) with several SNPs identified by GWAS. We performed a meta-analysis across ten cohorts of participants that showed a statistically significant association of rs13702 with triacylglycerols (TAG) (p = 3.18 × 10(-42)) and high-density lipoprotein cholesterol (HDL-C) (p = 1.35 × 10(-32)) with each copy of the minor allele associated with 0.060 mmol/l lower TAG and 0.041 mmol/l higher HDL-C. Our data showed that an LPL 3' UTR luciferase reporter carrying the rs13702 major T allele was reduced by 40% in response to a miR-410 mimic. We also evaluated the interaction between intake of dietary fatty acids and rs13702. Meta-analysis demonstrated a significant interaction between rs13702 and dietary polyunsaturated fatty acid (PUFA) with respect to TAG concentrations (p = 0.00153), with the magnitude of the inverse association between dietary PUFA intake and TAG concentration showing -0.007 mmol/l greater reduction. Our results suggest that rs13702 induces the allele-specific regulation of LPL by miR-410 in humans. This work provides biological and potential clinical relevance for previously reported GWAS variants associated with plasma lipid phenotypes.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

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.

Factors associated with six-year weight change in young and middle-aged adults in the Young Finns Study.

OBJECTIVE: To examine factors associated with weight change and obesity risk in young and middle-aged adults. SUBJECTS/METHODS: The Young Finns Study with its 923 women and 792 men aged 24-39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models. RESULTS: The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain > 2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high childhood BMI, high salt (NaCl and/or KCl) use, low number of children, low childhood family income, high stature and low level of dependence (a temperament subscale) were associated with increased weight gain (in the order of importance). In men (weight gain > 2 kg, n = 455), high stature, high intake of french fries, low intake of sweet cookies, young age, recent divorce, low intake of cereals, high intake of milk, depressive symptoms, rural childhood origin, high baseline BMI and unemployment were associated with more pronounced weight gain. Sedentarity (screen-time) was associated with weight gain only in young men. Physical activity and genetic risk for high BMI (score of 31 known variants) were not consistently associated with weight change. CONCLUSIONS: Socio-economic factors, temperamental and physical characteristics, and some dietary factors are related with weight change in young/middle-aged adults. The weight change occurring in adulthood is also determined by childhood factors, such as high BMI and low family income.

Role of childhood food patterns on adult cardiovascular disease risk.

Accumulating evidence indicates that childhood nutrition plays a role in the adulthood cardiovascular health. A lifelong tracking of dietary habits, following a long-term exposure to unhealthy dietary patterns or independent effects, is a potential effect-mediating mechanism. Dietary patterns have been studied by data-driven and hypothesis-based approaches. Typically, either data-driven healthy or prudent childhood dietary patterns have been characterized and found to be associated with lower adulthood cardiovascular disease (CVD) risk in the published cohort studies. With regard to the individual food groups or food quality indices, intakes particularly of vegetables and fruits (or fiber indicating plant food intake) and polyunsaturated fatty acids have shown protective effects. The evidence which could confirm the long-term healthiness of a hypothesis-based Mediterranean diet is limited, requiring further investigation. Overall, the recent literature strengthens the view that a healthy childhood diet is associated with lowered adulthood CVD risk.

Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: The American Heart Association (AHA) defined a new concept, cardiovascular health, and determined metrics needed to monitor it over time as part of its 2020 Impact Goal definition. Ideal cardiovascular health is defined by the presence of both ideal health behaviors and ideal health factors. The applicability of this concept to a cohort of children and its relationship with cardiometabolic outcomes in adulthood has not been reported. METHODS AND RESULTS: The sample comprised 856 participants aged 12 to 18 years (mean age 15.0 years) from the Cardiovascular Risk in Young Finns Study cohort. Participants were followed up for 21 years since baseline (1986) and had data available concerning health factors and behaviors in childhood and cardiometabolic outcomes in adulthood (2007). The number of ideal cardiovascular health metrics present in childhood was associated with reduced risk of hypertension (odds ratio [95% confidence interval] 0.66 [0.52-0.85], P<0.001), metabolic syndrome (0.66 [0.52-0.77], P<0.001), high low-density lipoprotein cholesterol (0.66 [0.52-0.85], P=0.001), and high-risk carotid artery intima-media thickness (0.75 [0.60-0.94], P=0.01) in adulthood. All analyses were age and sex adjusted, and the results were not altered after additional adjustment with socioeconomic status. CONCLUSIONS: The number of ideal cardiovascular health metrics present in childhood predicts subsequent cardiometabolic health in adulthood. Our findings suggest that pursuit of ideal cardiovascular health in childhood is important to prevent cardiometabolic outcomes in adulthood.

Childhood physical, environmental, and genetic predictors of adult hypertension: the cardiovascular risk in young Finns study.

BACKGROUND: Hypertension is a major modifiable cardiovascular risk factor. The present longitudinal study aimed to examine the best combination of childhood physical and environmental factors to predict adult hypertension and furthermore whether newly identified genetic variants for blood pressure increase the prediction of adult hypertension. METHODS AND RESULTS: The study cohort included 2625 individuals from the Cardiovascular Risk in Young Finns Study who were followed up for 21 to 27 years since baseline (1980; age, 3-18 years). In addition to dietary factors and biomarkers related to blood pressure, we examined whether a genetic risk score based on 29 newly identified single-nucleotide polymorphisms enhances the prediction of adult hypertension. Hypertension in adulthood was defined as systolic blood pressure ≥ 130 mm Hg and/or diastolic blood pressure ≥ 85 mm Hg or medication for the condition. Independent childhood risk factors for adult hypertension included the individual's own blood pressure (P<0.0001), parental hypertension (P<0.0001), childhood overweight/obesity (P=0.005), low parental occupational status (P=0.003), and high genetic risk score (P<0.0001). Risk assessment based on childhood overweight/obesity status, parental hypertension, and parental occupational status was superior in predicting hypertension compared with the approach using only data on childhood blood pressure levels (C statistics, 0.718 versus 0.733; P=0.0007). Inclusion of both parental hypertension history and data on novel genetic variants for hypertension further improved the C statistics (0.742; P=0.015). CONCLUSIONS: Prediction of adult hypertension was enhanced by taking into account known physical and environmental childhood risk factors, family history of hypertension, and novel genetic variants. A multifactorial approach may be useful in identifying children at high risk for adult hypertension.

Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts.

Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 U.S. and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG (ß = -0.004 mmol/L, 95% confidence interval: -0.005, -0.003) and FI (ß = -0.008 ln-pmol/L, 95% confidence interval: -0.009, -0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

Childhood serum fatty acid quality is associated with adult carotid artery intima media thickness in women but not in men.

Childhood nutrition may play a role in the development of cardiovascular disease risk in adulthood. We examined the links between childhood dietary fatty acid quality and adult subclinical atherosclerosis in a cohort of 374 males and 449 females, aged 3-18 y at baseline in 1980, followed for 27 y. Serum cholesterol ester fatty acid (CEFA) percentages were analyzed as markers of dietary fatty acid intake. Adulthood carotid artery intima media thickness (cIMT, µm), adjusted for childhood and adulthood lipid and nonlipid risk markers, was used as the outcome. In women, after adjustment for age and childhood nonlipid risk markers, the childhood saturated CEFA (B = 11.3; P = 0.011), monounsaturated CEFA (B = 2.5; P = 0.025), and n3 (ω3) polyunsaturated CEFA (B = 16.2; P = 0.035) percentages were directly associated with adult cIMT. In contrast, the n6 (ω6) polyunsaturated CEFA percentage was negatively associated with cIMT (B = -2.3; P = 0.008). Similar relationships were observed between childhood dietary intake data and adult cIMT. In men, these associations were generally weak and nonsignificant (P > 0.05) after controlling for confounders. These longitudinal data suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is associated with adult cIMT in women.

Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies.

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [ß = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.