Dataset Information

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.

ABSTRACT: 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 (? ± 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 ?-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).

SUBMITTER: McKeown NM

PROVIDER: S-EPMC5826559 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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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.

McKeown Nicola M NM Dashti Hassan S HS Ma Jiantao J Haslam Danielle E DE Kiefte-de Jong Jessica C JC Smith Caren E CE Tanaka Toshiko T Graff Mariaelisa M Lemaitre Rozenn N RN Rybin Denis D Sonestedt Emily E Frazier-Wood Alexis C AC Mook-Kanamori Dennis O DO Li Yanping Y Wang Carol A CA Leermakers Elisabeth T M ETM Mikkilä Vera V Young Kristin L KL Mukamal Kenneth J KJ Cupples L Adrienne LA Schulz Christina-Alexandra CA Chen Tzu-An TA Li-Gao Ruifang R Huang Tao T Oddy Wendy H WH Raitakari Olli O Rice Kenneth K Meigs James B JB Ericson Ulrika U Steffen Lyn M LM Rosendaal Frits R FR Hofman Albert A Kähönen Mika M Psaty Bruce M BM Brunkwall Louise L Uitterlinden Andre G AG Viikari Jorma J Siscovick David S DS Seppälä Ilkka I North Kari E KE Mozaffarian Dariush D Dupuis Josée J Orho-Melander Marju M Rich Stephen S SS de Mutsert Renée R Qi Lu L Pennell Craig E CE Franco Oscar H OH Lehtimäki Terho T Herman Mark A MA

Diabetologia 20171102 2

<h4>Aims/hypothesis</h4>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 ex ...[more]

PMID: 29098321

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Project description:Abstract Objectives Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Consumption of sugar-sweetened beverages (SSB) and genetic variants at the CHREBP (also known as MLXIPL) locus have separately been linked to dyslipidemia. We hypothesized that SSB intake may modify the associations between CHREBP variants and HDL-C and TG concentrations. Methods We conducted a cross-sectional analysis of data from 11 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium cohorts (N = 63,599). A total of 1606 single-nucleotide polymorphisms (SNPs) were selected within or near the CHREBP locus. SSB intake (sodas, fruit punches, lemonades, or other fruit drinks) was estimated from food-frequency questionnaires. Participants were grouped by five categories of SSB intake (ranging from < 1 serving/month to > 1 serving/day). Inverse-variance weighted fixed- and random-effect meta-analyses were used to quantify the following associations: 1) SSB consumption and HDL-C and TG concentrations; 2) selected SNPs and HDL-C and TG concentrations; and 3) interactions between SSB consumption and selected SNPs, and HDL-C and TG concentrations. Results were corrected for multiple testing to achieve a global p < 0.05. Results SSB intake was inversely associated with HDL-C and positively associated with TG concentrations (ptrend < 0.0001). We replicated previously observed GWAS associations between one distinct SNP on HDL-C (rs71556736) and two distinct SNPs (rs71556736 and rs13225660) on TG concentrations (Bonferroni-corrected P < 0.0001). Additionally, we identified two distinct novel SNP associations with TG concentrations (rs42124 and rs10245965). One distinct SNP displayed a statistically significant difference in effect size by category of SSB intake with HDL-C, where each additional minor allele at rs71556729 was significantly associated with HDL-C concentrations only among the highest SSB consumers [>1 serving/day: β (SE) = 4.47 (1.10) mg/dl, P = 5.0E-05; pinteract = 0.0001]. Additional SNPs displayed a suggestive difference in effect size for both HDL-C and TG concentrations. Conclusions Our results indicate that high SSB consumption may modify the association between genetic variants within or near the CHREBP locus and HDL-C and TG concentrations. Funding Sources NIH, AHA, USDA-ARS.

Project description:Abstract Objectives A meta-analysis of 11 CHARGE cohorts (N = 63,599) suggested that genetic variants within or near the CHREBP locus may modify the associations between sugar sweetened beverage (SSB) consumption and high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. The study objective was to replicate these findings in a large independent cohort. Methods Blood lipids and 24-hour recalls were available for 57,794 adults of European ancestry in the UK Biobank (2006-‘10). SSBs included “squash” and “fizzy” drinks derived from a single 24-hr recall. A total of 875 SNPs within or near the CHREBP locus were identified and included in this analysis. Associations between these SNPs and HDL-C and TG concentrations were quantified among participants who did not report SSB consumption (non-consumers, n = 45,866), reported ≥0.5 servings/day of SSB (consumers, n = 11,928), and a subset of consumers who reported ≥2 servings/day of SSB (high consumers, n = 3742). Interaction between SSB and selected SNPs on HDL-C and TG concentrations was evaluated by examining the difference in beta coefficients between strata. Results were considered statistically significant at a Bonferroni-corrected pinteract < 0.0001 (0.05/499 effective tests). Results A significant interaction between SSB consumption and TBL2-rs71556729 on HDL-C concentration previously observed in the meta-analysis was replicated in UK Biobank. However, we observed a stronger interaction for a SNP in high linkage disequilibrium (R2 = 0.93) FZD9-rs34821369 (MAF = 0.03, pinteract = 8.2E-05) with TBL2-rs71556729 (MAF = 0.03, pinteract = 0.0004). Among only SSB consumers, each additional minor G allele at FZD9-rs34821369 was associated with mean HDL-C concentrations 1.63 mg/dL (SE = 0.53, P = 0.002) higher than those with the major T allele. Conclusions Our results suggest that adults with the minor allele at FZD9-rs34821369 may be protected against SSB-induced low HDL-C concentrations. These results are consistent the findings from a prior meta-analysis of 11 cohorts. Funding Sources NIH, AHA, USDA-ARS. This research has been conducted using the UK Biobank Resource (Application Number 35,835).

Project description:BackgroundSugar-sweetened beverage (SSB) intake is a substantial source of energy in the diet of US children.ObjectiveWe examined the associations between mothers' child-feeding practices and SSB intake among 6-y-old children.MethodsWe analyzed data from the Year 6 Follow-up of the Infant Feeding Practices Study II in 1350 US children aged 6 y. The outcome variable was child's SSB intake. The exposure variables were 4 child-feeding practices of mothers: setting limits on sweets or junk foods, regulating their child's favorite food intake to prevent overconsumption, pressuring their child to eat enough, and pressuring their child to "clean the plate." We used multinomial logistic regression and controlled for child and maternal characteristics. Analyses were stratified on child weight status.ResultsThe consumption of SSBs ?1 time/d was observed among 17.1% of underweight/normal-weight children and in 23.2% of overweight/obese children. Adjusted ORs (aORs) of consuming SSBs ?1 time/d (vs. no SSB consumption) were significantly lower in children whose mothers reported setting limits on sweets/junk foods (aOR: 0.29; 95% CI: 0.15, 0.58 for underweight/normal-weight children; aOR: 0.16; 95% CI: 0.03, 0.79 for overweight/obese children). SSB intake was higher among underweight/normal-weight children whose mothers reported trying to keep the child from eating too much of their favorite foods (aOR: 2.03; 95% CI: 1.25, 3.29). Mothers' tendency to pressure their children to consume more food or to "clean the plate" was not associated with child's SSB intake.ConclusionsSSBs were commonly consumed by young children. The odds of daily SSB intake were lower among children whose mothers set limits on sweets/junk foods regardless of child's weight but were higher among underweight/normal-weight children whose mothers restricted the child's favorite food intake. Future studies can investigate the impact of alternatives to restrictive feeding practices that could reduce children's SSB intake.

Dataset Information

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.

Publications

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.

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