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).

Association between lutein intake and lung function in adults: the Rotterdam Study.

Lutein, a fat-soluble carotenoid with antioxidant properties, may have an effect on respiratory health. However, the evidence is inconsistent. We aimed to cross-sectionally investigate the association between lutein intake and lung function by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC% in adults (aged 45-79 years). We included 4402 participants from the Rotterdam Study, a prospective cohort study in The Netherlands. Lutein intake was assessed using a validated FFQ. Lung function was assessed using spirometry around the same time point as the dietary assessment. No independent association was found between lutein intake and FEV1 (-12·17 (95 % CI -34·21, 9·87) ml per sd increase in lutein) after adjustment for age, sex, height, cohort effect, ethnicity, education, weight, total daily energy intake, smoking status, physical activity, and intakes of fatty acids, dietary fibre, alcohol, ß-carotene, ß-crypotoxanthin, lycopene and zeaxanthin. There was also no association between lutein and FVC or FEV1/FVC%. However, after stratification by smoking status, lutein intake was significantly associated with lower FEV1/FVC% in current smokers (-1·69 (95 % CI -2·93, -0·45) % per sd increase of lutein) independent of other carotenoids. The present study does not support an independent association between lutein intake and lung function in adults. However, future studies should focus on the potential inverse association between high lutein intake and lung function in specific risk groups such as smokers.

A priori and a posteriori dietary patterns at the age of 1 year and body composition at the age of 6 years: the Generation R Study.

Dietary patterns have been linked to obesity in adults, however, not much is known about this association in early childhood. We examined associations of different types of dietary patterns in 1-year-old children with body composition at school age in 2026 children participating in a population-based cohort study. Dietary intake at the age of 1 year was assessed with a food-frequency questionnaire. At the children's age of 6 years we measured their body composition with dual-energy X-ray absorptiometry and we calculated body mass index, fat mass index (FMI), and fat-free mass index (FFMI). Three dietary pattern approaches were used: (1) An a priori-defined diet quality score; (2) dietary patterns based on variation in food intake, derived from principal-component-analysis (PCA); and (3) dietary patterns based on variations in FMI and FFMI, derived with reduced-rank-regression (RRR). Both the a priori-defined diet score and a 'Health-conscious' PCA-pattern were characterized by a high intake of fruit, vegetables, grains, and vegetable oils, and, after adjustment for confounders, children with higher adherence to these patterns had a higher FFMI at 6 years [0.19 SD (95 % CI 0.08;0.30) per SD increase in diet score], but had no different FMI. One of the two RRR-patterns was also positively associated with FFMI and was characterized by intake of whole grains, pasta and rice, and vegetable oils. Our results suggest that different a priori- and a posteriori-derived health-conscious dietary patterns in early childhood are associated with a higher fat-free mass, but not with fat mass, in later childhood.

Longitudinal association between preschool fussy eating and body composition at 6 years of age: The Generation R Study.

BACKGROUND: Children's fussy eating behavior has been related to both underweight and overweight in cross-sectional studies, but the direction of these associations and the relation with more detailed measures of body composition remains unclear. We aimed to examine whether fussy eating at age 4 years is longitudinally related to body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI) at 6 years of age. METHODS: This study was embedded in Generation R, a population-based, prospective cohort. Data were available for 4191 children. The Children's Eating Behaviour Questionnaire (CEBQ), administered at age 4 years, was used to derive a fussy eating profile. This profile is characterized by high scores on food avoidant scales and low scores on food approach scales. At age 6 years, height and weight were measured at our research center. Body fat and fat-free mass were measured using Dual-energy-X-ray absorptiometry. We used age- and sex-specific standard deviation scores (SDS) for all outcomes. RESULTS: After adjustment for confounders, the fussy eating profile was related to lower BMI-SDS (B = -0.37, 95% CI: -0.47;-0.26), lower FMI-SDS (B = -0.22, 95 % CI: -0.33;-0.12) and lower FFMI-SDS (B = -0.41, 95% CI: -0.54;-0.29). When adjusting for baseline BMI at 4 years, the fussy eating profile predicted a 0.11 lower BMI-SDS at age 6 (95% CI: -0.19;-0.04). This change in BMI was mainly due to a decrease in FFMI (B = -0.19, 95% CI: -0.29;-0.09). Fussy eaters also had a higher risk of becoming underweight than non-fussy eaters (OR = 2.28, 95% CI: 1.34;3.87). CONCLUSIONS: Our findings suggest that young fussy eaters are at risk of having a lower fat free mass and of becoming underweight over a 2-year period. This implies that fussy eaters may benefit from careful monitoring to prevent an adverse growth development.

Sugar-containing beverage intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study.

BACKGROUND: Consumption of sugar-containing beverages (SCBs) in adults has been associated with an increased risk of metabolic syndrome. Although the effect of SCB on body weight in children is well established, little is known about the cardiometabolic effects in young children. We studied the associations of SCB intake at the age of 1 year with cardiometabolic health at age 6 years. METHODS: This study was performed among 2,045 Dutch children from a population based prospective birth cohort. SCB intake was assessed with a semi-quantitative food frequency questionnaire at the age of 13 months and sex-specific tertiles were created. Children visited the research center at the age of 6 years. We created a continuous cardiometabolic risk factor score including: body fat percentage, blood pressure, insulin, HDL-cholesterol and triglycerides. Age-and sex-specific standard deviation (SD) scores were created for all outcomes. Multivariable linear regression was performed with adjustment for socio-demographic and lifestyle variables of mother and child. RESULTS: In the total population, we observed an association between higher SCB intake at 13 months of age and a higher cardiometabolic risk factor score at the age of 6 years (0.13SD (95 % CI 0.01; 0.25), highest vs. lowest tertile) After stratification by sex, we found that boys in the highest tertile of SCB intake had a higher cardiometabolic risk factor score (0.18 SD (95 % CI 0.01; 0.34)), as compared to boys in the lowest tertile of SCB intake. There was no significant association in girls. We did not find associations of SCB intake with the individual cardiometabolic risk factors in the total population, or in the stratified analyses. CONCLUSION: Higher SCB intake at 1 year of age was associated with a higher cardiometabolic risk factor score at age 6 years in boys, but not in girls. Further research on sex-specific effects of SCBs is needed.

Lutein intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study.

Lutein is a carotenoid with strong antioxidant properties. Previous studies in adults suggest a beneficial role of lutein on cardiometabolic health. However, it is unknown whether this relation also exists in children; therefore, we aimed to assess the relation between lutein intake at 13 months of age and cardiometabolic outcomes at the age of 6 years. We included 2044 Dutch children participating in a population-based prospective cohort study. Diet was measured at 13 months of age with an FFQ. Lutein intake was standardised for energy and ß-carotene intake. Blood pressure, anthropometrics, serum lipids and insulin were measured at the age of 6 years. Dual-energy X-ray absorptiometry was performed to measure total and regional fat and lean mass. A continuous cardiometabolic risk factor score was created, including the components body fat percentage, blood pressure, insulin, HDL-cholesterol and TAG. Age- and sex-specific standard deviation scores were created for all outcomes. Multivariable linear regression was performed, including socio-demographic and lifestyle variables. Median (energy-standardised) lutein intake was 1317 mcg/d (95% range 87, 6069 mcg/d). There were no consistent associations between lutein intake at 13 months and anthropometrics and body composition measures at 6 years of age. In addition, lutein intake was not associated with a continuous cardiometabolic risk factor score, nor was it associated with any of the individual components of the cardiometabolic risk factor score. Results from this large population-based prospective cohort study do not support the hypothesis that lutein intake early in life has a beneficial role for later cardiometabolic health.

Effects of protein intake on blood pressure, insulin sensitivity and blood lipids in children: a systematic review.

High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.

Maternal weight, gestational weight gain and preschool wheezing: the Generation R Study.

We studied the associations of maternal pre-pregnancy body mass index and gestational weight gain with risks of preschool wheezing in offspring and explored the role of growth, infectious and atopic mechanisms. This substudy of 4656 children was embedded in a population-based birth cohort. Information about maternal pre-pregnancy weight, gestational weight gain and wheezing at the ages of 1-4 years was obtained by either physical measurements or questionnaires. Among mothers with a history of asthma or atopy, maternal pre-pregnancy obesity was associated with an overall increased risk of preschool wheezing (odds ratio 1.47, 95% confidence interval 1.12-1.95). Also, each standard deviation increase of gestational weight gain was associated with an increased overall risk of preschool wheezing (1.09, 1.04-1.14), was independent of pre-pregnancy body mass index and was not different between mothers with and without a history of asthma or atopy. Child's growth, respiratory tract infections or eczema did not alter the results. Mothers with pre-pregnancy obesity and a history of asthma or atopy, and mothers with higher gestational weight gain showed higher risks of wheezing in their offspring. These associations could not be explained by growth, infectious or atopic mechanisms. Further research is needed to identify underlying mechanisms and long-term consequences.

A priori and a posteriori derived dietary patterns in infancy and cardiometabolic health in childhood: The role of body composition.

BACKGROUND & AIMS: Cardiometabolic risk has its origins in early life. However, it is unclear whether diet during early childhood is associated with cardiometabolic health, and what the role is of obesity. We aimed to study whether overall diet during early childhood is associated with cardiometabolic health and to examine if difference in body composition explain this association. METHODS: We examined associations of different types of dietary patterns in infancy with cardiometabolic health at school age among 2026 Dutch children participating in a population-based cohort in the Netherlands. Food intake at the age of 1 year was assessed with a food-frequency questionnaire. Three dietary pattern approaches were used: 1) An a priori-defined diet quality score; 2) dietary patterns based on variation in food intake, derived from principal component analysis (PCA); and 3) dietary patterns based on variations in fat and fat-free mass index, derived with reduced-rank regression (RRR). At the children's age of 6 years, we measured their body composition, systolic and diastolic blood pressure, and serum concentrations of insulin, triglycerides, and HDL-cholesterol, which we combined in a cardiometabolic risk-factor score. RESULTS: We observed that, after adjustment for confounders, children with higher adherence to a 'Health-conscious' PCA-derived pattern had a lower cardiometabolic risk-factor score (-0.07 SD (95%CI -0.12; -0.02) per SD). This association did not change after adjustment for fat and fat-free mass index. The RRR-derived dietary patterns based on variations in body composition were not associated with the cardiometabolic risk-factor score. CONCLUSIONS: Our results suggest that diet in early childhood may affect cardiometabolic health independent of differences in body composition.

Maternal dietary patterns during pregnancy and offspring cardiometabolic health at age 6 years: The generation R study.

BACKGROUND & AIMS: Maternal nutrition during pregnancy might be important in influencing offspring cardiometabolic health. However, research has focused mostly on specific nutrients or total energy, and possible effects of whole diet are unclear. We aimed to assess the associations between different dietary patterns during pregnancy and offspring cardiometabolic health among 2592 mother-child pairs from Generation R, a prospective population-based cohort study from fetal life onwards in Rotterdam, the Netherlands. METHODS: Maternal diet was assessed in early pregnancy with a food-frequency questionnaire. We identified three a posteriori-dietary patterns, namely a 'Vegetable, fish and oil', 'Nuts, soy and high-fiber cereals' and 'Margarine, snacks and sugar'-pattern. An a priori-pattern was created based on the 'Dutch Healthy Diet Index'. Cardiometabolic health (pulse wave velocity, blood pressure, insulin, HDL-cholesterol and triglycerides) was measured at the child's age of 6 years. RESULTS: In the crude models, the 'Vegetable, fish and oil', 'Nuts, soy and high-fiber cereals' and 'Dutch Healthy Diet Index' seemed beneficial, as higher adherence to these patterns was significantly associated with lower blood pressure and lower pulse wave velocity. After adjustment for other socio-demographic and lifestyle factors, most associations disappeared, except for lower pulse wave velocity with the 'Vegetable, fish and oil'-dietary pattern (-0.19 SD (95% CI -0.33; -0.06), highest quartile of adherence vs. lowest quartile). No associations were found between maternal dietary patterns and offspring blood lipids or insulin levels. CONCLUSIONS: Our results suggest that there are no consistent independent associations of maternal dietary patterns with offspring cardiometabolic health at 6 years.

The effects of lutein on respiratory health across the life course: A systematic review.

BACKGROUND: Lutein, a fat-soluble carotenoid present in green leafy vegetables and eggs, has strong antioxidant properties and could therefore be important for respiratory health. DESIGN: We systematically reviewed the literature for articles that evaluated associations of lutein (intake, supplements or blood levels) with respiratory outcomes, published in Medline, Embase, Cochrane Central, PubMed, Web of Science and Google Scholar, up to August 2014. RESULTS: We identified one Randomized Control Trial (RCT), two longitudinal, four prospective and six cross-sectional studies. The individual studies obtained a Quality Score ranging between 3 and 9. Six studies were performed in children, which examined bronchopulmonary dysplasia (BPD), asthma and wheezing. In adults, 7 studies investigated asthma, respiratory function and respiratory mortality. The RCT found a borderline significant effect of lutein/zeaxanthin supplementation in neonates on the risk of BPD (OR 0.43 (95% CI 0.15; 1.17). No association was found between lutein intake or levels and respiratory outcomes in children. A case-control study in adults showed lower lutein levels in asthma cases. Three studies, with a prospective or longitudinal study design, in adults found a small but a significant positive association between lutein intake or levels and respiratory function. No association was found in the other two studies. In relation to respiratory mortality, one longitudinal study showed that higher lutein blood levels were associated with a decreased mortality (HR 0.77 (95% CI 0.60; 0.99), per SD increase in lutein). CONCLUSION: The published literature suggests a possible positive association between lutein and respiratory health. However, the literature is scarce and most studies are of observational nature.

A Priori and a Posteriori Dietary Patterns during Pregnancy and Gestational Weight Gain: The Generation R Study.

Abnormal gestational weight gain (GWG) is associated with adverse pregnancy outcomes. We examined whether dietary patterns are associated with GWG. Participants included 3374 pregnant women from a population-based cohort in the Netherlands. Dietary intake during pregnancy was assessed with food-frequency questionnaires. Three a posteriori-derived dietary patterns were identified using principal component analysis: a "Vegetable, oil and fish", a "Nuts, high-fiber cereals and soy", and a "Margarine, sugar and snacks" pattern. The a priori-defined dietary pattern was based on national dietary recommendations. Weight was repeatedly measured around 13, 20 and 30 weeks of pregnancy; pre-pregnancy and maximum weight were self-reported. Normal weight women with high adherence to the "Vegetable, oil and fish" pattern had higher early-pregnancy GWG than those with low adherence (43 g/week (95% CI 16; 69) for highest vs. lowest quartile (Q)). Adherence to the "Margarine, sugar and snacks" pattern was associated with a higher prevalence of excessive GWG (OR 1.45 (95% CI 1.06; 1.99) Q4 vs. Q1). Normal weight women with higher scores on the "Nuts, high-fiber cereals and soy" pattern had more moderate GWG than women with lower scores (-0.01 (95% CI -0.02; -0.00) per SD). The a priori-defined pattern was not associated with GWG. To conclude, specific dietary patterns may play a role in early pregnancy but are not consistently associated with GWG.

Effects of choline on health across the life course: a systematic review.

CONTEXT: Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it may influence blood lipid levels because it is an essential component of very-low-density lipoproteins. OBJECTIVE: The aim was to systematically review, using PRISMA guidelines, the literature pertaining to the effects of choline on body composition and on metabolic, cardiovascular, respiratory, and neurological outcomes in different life stages. DATA SOURCES: The MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar databases were searched up to July 2014. DATA EXTRACTION: Fifty relevant articles were identified. These comprised trials and cohort, case-control, and cross-sectional studies that assessed blood levels of choline, dietary intake of choline, and supplementation with choline in a population free of diseases at baseline. DATA SYNTHESIS: There is some observational evidence that choline during pregnancy may be beneficial for the neurological health of the child. In adults, choline may have beneficial effects on cognition, but high-quality (intervention) studies are lacking. Results on the effects of choline on body composition, blood lipids, and cardiovascular health were inconsistent. CONCLUSIONS: Evidence to confirm the suggested effects of choline on health in different stages of life is scarce. Potential effects of choline need to be confirmed by intervention studies. Possible harmful effects on cardiometabolic health need careful evaluation.

Health in children: a conceptual framework for use in healthy ageing research.

OBJECTIVE: With increasing life expectancy, there is a focus on "healthy ageing". Most activities in this area focus on the elderly. However, the ageing process starts much earlier. Childhood offers an important window to lay a base for future healthy ageing. Thus, to address the full ageing process, we should include younger populations in ageing research. If we aim for healthy ageing across the life course, we need to clarify the meaning of health at different ages. The aim of this paper was to develop a conceptual framework for child health, which can be used as a starting point for healthy ageing research from a life course perspective. RESULTS: We conceptualize child health as: "a dynamic state, not merely the absence of disease or disability, but also adequate resilience that permits optimal physical, mental, and social functioning, and optimal quality of life in order to achieve full potential and to become an independent, functional, and social individual." We propose five core dimensions of child health: Absence of physical disease; absence of psychiatric disorders; optimal physical, mental, and social functioning, including adequate development; good quality of life or well-being; and adequate resilience. CONCLUSION: This conceptualization of child health and its dimensions can be seen as a first step towards building a framework for future studies into healthy ageing across the life course.

A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the generation R study.

OBJECTIVE: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. METHODS: This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. RESULTS: Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences -0.23 mm (95%CI -0.45 to -0.00) and -0.41 mm (95%CI -0.69 to -0.13), respectively] and a smaller birth length [difference -2.61 mm (95%CI -5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity. CONCLUSIONS: Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene--fetal smoke exposure interactions.