Kim Ve Braun

Protein intake in early childhood and body composition at the age of 6 years: The Generation R Study

Background:Previous studies suggest that high protein intake in infancy leads to a higher body mass index (BMI) in later childhood. We examined the associations of total, animal and vegetable protein intake in early childhood with detailed measures of body composition at the age of 6 years.Methods:This study was performed in 2911 children participating in a population-based cohort study. Protein intake at the age of 1 year was assessed with a validated food-frequency questionnaire and was adjusted for total energy intake. At the children’s age of 6 years, we measured their anthropometrics and body fat (with dual-energy X-ray absorptiometry). We calculated age- and sex-specific s.d. scores for BMI, fat mass index (FMI) and fat-free mass index (FFMI).Results:After adjustment for confounders, a 10 g per day higher total protein intake at 1 year of age was associated with a 0.05 s.d. (95% confidence interval (CI) 0.00, 0.09) higher BMI at age 6. This association was fully driven by a higher FMI (0.06 s.d. (95%CI 0.01, 0.11)) and not FFMI (−0.01 s.d. (95%CI −0.06, 0.05)). The associations of protein intake with FMI at 6 years remained significant after adjustment for BMI at the age of 1 year. Additional analyses showed that the associations of protein intake with FMI were stronger in girls than in boys (P for interaction=0.03), stronger among children who had catch-up growth in the first year of life (P for interaction<0.01) and stronger for intake of animal protein (both dairy and non-dairy protein) than protein from vegetable sources.Conclusions:Our results suggest that high protein intake in early childhood is associated with higher body fat mass, but not fat-free mass. Future studies are needed to investigate whether these changes persist into adulthood and to examine the optimal range of protein intake for infants and young children.

Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study

BackgroundDNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants.ResultsGenome-wide methylation levels were measured in whole blood using the Illumina Methylation 450 array. Associations between lipid levels and DNA methylation beta values were examined using linear mixed-effect models. All models were adjusted for sex, age, smoking, white blood cell proportions, array number, and position on array. A Bonferroni-corrected p value lower than 1.08 × 10−7 was considered statistically significant. Five CpG sites annotated to genes including DHCR24, CPT1A, ABCG1, and SREBF1 were identified and replicated. Four CpG sites were associated with triglycerides, including CpG sites annotated to CPT1A (cg00574958 and cg17058475), ABCG1 (cg06500161), and SREBF1 (cg11024682). Two CpG sites were associated with HDL-C, including ABCG1 (cg06500161) and DHCR24 (cg17901584). No significant associations were observed with LDL-C or total cholesterol.ConclusionsWe report an association of HDL-C levels with methylation of a CpG site near DHCR24, a protein-coding gene involved in cholesterol biosynthesis, which has previously been reported to be associated with other metabolic traits. Furthermore, we confirmed previously reported associations of methylation of CpG sites within CPT1A, ABCG1, and SREBF1 and lipids. These results provide insight in the mechanisms that are involved in lipid metabolism.

The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.

BACKGROUND New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences. AIM To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR). METHOD AND RESULTS Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies. CONCLUSIONS AND RELEVANCE Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.

Effects of polyunsaturated fatty acid intake and status during pregnancy, lactation, and early childhood on cardiometabolic health: A systematic review

The importance of polyunsaturated fatty acid (PUFA) intake in fetal life and infancy has been widely studied in relation to child cognitive and visual development, but whether early life PUFA exposure is related to cardiometabolic risk factors is unclear. The focus of this systematic review was to evaluate the effects of PUFA dietary intake and blood levels during pregnancy, lactation, or early childhood (⩽5 y) on obesity, blood pressure, blood lipids, and insulin sensitivity. We identified 4302 abstracts in the databases Embase, Medline and Cochrane Central (April 2014), of which 56 articles, reporting on 45 unique studies, met all selection criteria. Many of the included studies focused on obesity as an outcome (33 studies), whereas studies on insulin sensitivity were relatively scarce (6 studies). Overall, results for obesity, blood pressure, and blood lipids were inconsistent, with a few studies reporting effects in opposite directions and other studies that did not observe any effects of PUFAs on these outcomes. Four studies suggested beneficial effects of PUFAs on insulin sensitivity. We conclude that there is insufficient evidence to support a beneficial effect of PUFAs in fetal life or early childhood on obesity, blood pressure, or blood lipids. More research is needed to investigate the potential favorable effects of PUFAs on insulin sensitivity, and to examine the role of specific fatty acids in early life on later cardiometabolic health.

The role of DNA methylation in dyslipidaemia: A systematic review.

Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby affect cardiovascular health. We aimed to systematically review studies investigating the association between epigenetic marks and plasma concentrations of triacylglycerol, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Six medical databases were searched until September 3rd 2015, reference lists were screened, and experts in the field were contacted. Of the 757 identified references, 31 articles reporting on 23 unique studies met all inclusion criteria. These studies included data on 8027 unique participants. Overall, no consistent associations were observed between global DNA methylation and blood lipids. Candidate gene and epigenome-wide association studies reported epigenetic regulation of several genes to be related with blood lipids, of which results for ABCG1, CPT1A, TNNT1, MIR33B, SREBF1, and TNIP were replicated. To date, no studies have been performed on histone modification in relation to blood lipids. To conclude, promising results have been reported in the field of epigenetics and dyslipidaemia, however, further rigorous studies are needed to expand our understanding on the role of epigenetics in regulating humans blood lipid levels and its effects on health and disease.

Dietary Intakes of Folic Acid and Methionine in Early Childhood Are Associated with Body Composition at School Age

BACKGROUND Deficiency of vitamin B-6, vitamin B-12, folate, folic acid, or methionine may lead to dysregulation of DNA methylation, which might lead to disturbed energy and lipid metabolism. OBJECTIVE We aimed to explore whether intakes of vitamin B-6, vitamin B-12, folate, folic acid, and methionine at 1 y are associated with measures of growth and body composition at the age of 6 y. METHODS This study was performed in 2922 children participating in The Generation R Study, a population-based prospective cohort study. Dietary intakes of vitamins B-6 and B-12, folate, folic acid, and methionine were assessed at a median age of 12.9 mo by using a validated food-frequency questionnaire. At the age of 6 y, height and weight were measured, and body mass index (BMI; in kg/m(2)) was calculated. Body fat was measured with dual-energy X-ray absorptiometry, and body fat percentage and the ratio of android fat mass to gynoid fat mass (android:gynoid) were calculated. RESULTS In models adjusted for maternal and child characteristics, children with folic acid intakes in the highest tertile had a 0.16 SD score (SDS) lower weight (95% CI: -0.31, -0.02 SDS) and a 0.14 SDS lower BMI (95% CI: -0.26, -0.01 SDS) than children in the lowest tertile. Children with vitamin B-12 intakes in the highest tertile had a 0.13 SDS higher android:gynoid (95% CI: 0.00, 0.25 SDS) than children in the lowest tertile. In addition, children with intakes in the highest tertile of methionine had a 0.09 SDS higher BMI (95% CI: 0.01, 0.17) and a 0.12 SDS higher android:gynoid (95% CI: 0.02, 0.22) than children in the lowest tertile. Vitamin B-6 and folate intakes were not associated with any of the body composition outcomes measured. CONCLUSIONS In this population of children, early high folic acid intakes were associated with a lower body weight and BMI at the age of 6 y. In contrast, early higher methionine intakes were associated with unfavorable body composition at the age of 6 y. Future studies should investigate long-term consequences of these outcomes on health.

Intake of Different Types of Fatty Acids in Infancy Is Not Associated with Growth, Adiposity, or Cardiometabolic Health up to 6 Years of Age

Background: Studies in adults indicate that a lower saturated and higher unsaturated fat intake is associated with a lower risk of metabolic syndrome and cardiovascular diseases. However, studies on fat intake in relation to cardiometabolic health during childhood are scarce.Objective: We examined associations between dietary intake of fatty acids (FAs) at age 1 y and measures of growth, adiposity, and cardiometabolic health up to age 6 y.Methods: This study was conducted in 2927 children participating in the Generation R Study, a multiethnic, prospective, population-based cohort in the Netherlands. We measured childrens total fat intake and intakes of saturated FAs (SFAs), monounsaturated FAs (MUFAs), and polyunsaturated FAs (PUFAs) at a median age of 12.9 mo (95% range: 12.2, 18.9 mo) with a food-frequency questionnaire. We repeatedly measured their height and weight up to age 6 y. At 6 y of age, we measured body fat percentage, diastolic and systolic blood pressure, and serum insulin, triacylglycerol, and HDL cholesterol. These outcomes were combined into a cardiometabolic risk factor score. We examined associations of FA intake with repeated measures of height, weight, and body mass index by using linear mixed models and with cardiometabolic outcomes by using linear regression models, adjusting for sociodemographic and lifestyle factors and taking into account macronutrient substitution effects.Results: In multivariable models, we observed no associations of a higher intake of total fat or SFAs, MUFAs, or PUFAs with growth, adiposity, or cardiometabolic health when fat was consumed at the expense of carbohydrates. In subsequent models, there were also no associations observed for higher MUFA or PUFA intakes at the expense of SFAs with any of the outcomes. Results did not differ by sex, ethnicity, age, or birth weight.Conclusion: The results of this study did not support our hypothesis that intake of different types of FAs was associated with adiposity or cardiometabolic health among children.

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat, protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15 – 0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood poverty (|rg| ≈ 0.1 – 0.3). Overall, our results show that the relative intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations suggestive of health implications beyond caloric content.

The Role of Epigenetic Modifications in Cardiometabolic Diseases

The risk of cardiometabolic disease such as type II diabetes and cardiovascular disease (CVD) increases with age. Both of these diseases are important determinants of overall health and longevity. Although environmental and genetic studies have improved our understanding of the etiology and pathophysiologic mechanisms associated with diabetes and CVD, the etiology for the majority of these traits remains poorly understood. Alterations in the epigenetic mechanisms, including DNA methylation and histone modification, have been recently implicated in the onset and progression of cardiometabolic outcomes and may account for the missing heritability determinants of these diseases. Despite a growing body of literature addressing the role of the environment in gene expression affecting cardiometabolic risk, little is known about the epigenetic pathways involved in the pathophysiology of diabetes and CVD. In this chapter we describe the current knowledge about epigenetic control mechanisms in the development of cardiometabolic diseases.

Longitudinal association of dietary protein intake in infancy and adiposity throughout childhood

BACKGROUND & AIMS Protein intake in infancy promotes growth, but excessive intake may lead to adiposity in children. However, whether this increased adiposity persists throughout childhood and is independent of diet in later life remains unclear. Therefore, we studied the associations of total protein intake and protein from different sources at age 1 year with repeatedly measured growth and body composition up to age 10 years. Additionally, we examined whether these associations are independent of protein intake and overall diet quality at age 8 years. METHODS We included 3573 children from the Generation R study, a population-based prospective cohort in the Netherlands. Dietary intakes were assessed with food-frequency questionnaires at ages 1 and 8 years and macronutrient intakes were expressed as energy percentages (E%). Height and weight were measured at eight time points between ages 1 and 10 years. Fat and fat-free masses were measured at ages 6 and 10 years with dual-energy X-ray-absorptiometry. We calculated body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI). Outcomes were standardized for sex and age and expressed as standard deviation scores (SDS). Associations of protein intake with growth and body composition trajectories were examined with multivariable linear mixed models. RESULTS After adjustment for confounders, 5E% additional protein intake at age 1 year was associated with a 0.10 SDS higher weight (95% CI 0.04, 0.16), 0.10 SDS higher BMI (95% CI 0.04, 0.16), and 0.07 SDS higher FMI (95% CI 0.01, 0.13) up to age 10 years. These associations were explained by protein from animal sources and not plant sources. Associations were independent of protein intake and overall diet quality at age 8 years, and were independent of whether higher protein was consumed at the expense of carbohydrates or fat in the diet. CONCLUSIONS Our study suggests that high protein intake in infancy, particularly from animal food sources, is persistently associated with adiposity up to age 10 years. Restricting protein intake in this critical period of development may aid in the early prevention of adiposity in childhood.