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1.
BMJ ; 366: l4292, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345923

RESUMO

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Adulto , Alelos , Diabetes Mellitus Tipo 2/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
2.
Eur J Nutr ; 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31076856

RESUMO

PURPOSE: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per µgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

3.
Clin Nutr ; 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29914777

RESUMO

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.

4.
Am J Epidemiol ; 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29762635

RESUMO

We conducted an epigenome-wide association study on obesity-related traits. We used data from two prospective, population-based cohort studies: the Rotterdam Study (RS) (2006-2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990-1992). We used RS (n = 1,454) as the discovery panel and ARIC (n = 2,097) as replication panel. Linear mixed-effect models were used to assess the cross-sectional association between genome-wide DNA methylation in leukocytes with body mass index (BMI) and waist circumference (WC) adjusting for sex, age, smoking, leukocyte proportions, array number and position on array. The two latter were modelled as random effects. Fourteen CpGs were associated with BMI and 26 CpGs with WC in RS after Bonferroni-correction (P < 1.07 × 10-7), of which 12 and 13 CpGs replicated in ARIC Study, respectively. The most significant novel CpGs were located at MSI2 (cg21139312) and LARS2 (cg18030453) and were associated both with BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations of methylation at MSI2 and LARS2 with obesity-related traits. These results provide further insight in mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.

5.
Clin Epigenetics ; 9: 15, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28194238

RESUMO

BACKGROUND: DNA 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. RESULTS: Genome-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. CONCLUSIONS: We 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.


Assuntos
Ilhas de CpG , Metilação de DNA , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Carnitina O-Palmitoiltransferase/genética , Estudos de Coortes , Epigênese Genética , Epigenômica/métodos , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
6.
Prog Lipid Res ; 64: 178-191, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27746199

RESUMO

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 human's blood lipid levels and its effects on health and disease.


Assuntos
Metilação de DNA , Dislipidemias/patologia , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/genética , Dislipidemias/metabolismo , Epigenômica , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Triglicerídeos/sangue
7.
Nutrients ; 8(9)2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27589791

RESUMO

Dietary fiber (DF) intake may be beneficial for cardiometabolic health. However, whether this already occurs in early childhood is unclear. We investigated associations between DF intake in infancy and cardiometabolic health in childhood among 2032 children participating in a population-based cohort in The Netherlands. Information on DF intake at a median age of 12.9 months was collected using a food-frequency questionnaire. DF was adjusted for energy intake using the residual method. At age 6 years, body fat percentage, high-density lipoprotein (HDL)-cholesterol, insulin, triglycerides, and blood pressure were assessed and expressed in age- and sex-specific standard deviation scores (SDS). These five factors were combined into a cardiometabolic risk factor score. In models adjusted for several parental and child covariates, a higher DF intake was associated with a lower cardiometabolic risk factor score. When we examined individual cardiometabolic factors, we observed that a 1 g/day higher energy-adjusted DF intake was associated with 0.026 SDS higher HDL-cholesterol (95% CI 0.009, 0.042), and 0.020 SDS lower triglycerides (95% CI -0.037, -0.003), but not with body fat, insulin, or blood pressure. Results were similar for DF with and without adjustment for energy intake. Our findings suggest that higher DF intake in infancy may be associated with better cardiometabolic health in later childhood.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta , Fibras na Dieta/administração & dosagem , Fenômenos Fisiológicos da Nutrição do Lactente , Doenças Metabólicas/prevenção & controle , Estado Nutricional , Adiposidade , Fatores Etários , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Criança , Desenvolvimento Infantil , Pré-Escolar , HDL-Colesterol/sangue , Dieta/efeitos adversos , Ingestão de Energia , Feminino , Indicadores Básicos de Saúde , Humanos , Lactente , Insulina/sangue , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/etiologia , Países Baixos , Avaliação Nutricional , Inquéritos Nutricionais , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangue
8.
J Nutr ; 145(9): 2123-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26203097

RESUMO

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.


Assuntos
Composição Corporal , Fenômenos Fisiológicos da Nutrição Infantil , Ácido Fólico/administração & dosagem , Metionina/administração & dosagem , Absorciometria de Fóton , Adiposidade , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Lactente , Masculino , Países Baixos , Avaliação Nutricional , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Vitamina B 12/administração & dosagem , Vitamina B 6/administração & dosagem
9.
Prog Lipid Res ; 59: 67-87, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26025302

RESUMO

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.


Assuntos
Doenças Cardiovasculares/metabolismo , Ácidos Graxos Insaturados/metabolismo , Obesidade Pediátrica/metabolismo , Animais , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Ingestão de Alimentos , Feminino , Humanos , Resistência à Insulina , Lactação , Metabolismo dos Lipídeos , Obesidade Pediátrica/etiologia , Gravidez
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