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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. ; Dashti, Hassan S. ; Ma, Jiantao ; Haslam, Danielle E. ; Kiefte-de Jong, Jessica C. ; Smith, Caren E. ; Tanaka, Toshiko ; Graff, Mariaelisa ; Lemaitre, Rozenn N. and Rybin, Denis , et al. (2018) In Diabetologia 61(2). p.317-330
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... (More)

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 (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10−3) and higher fasting insulin (0.030 ± 0.005 [loge 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 β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 loge 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.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).

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type
Contribution to journal
publication status
published
subject
keywords
Carbohydrate metabolism, Epidemiology, Genetics, Meta-analysis, Nutrition, Type 2 diabetes
in
Diabetologia
volume
61
issue
2
pages
317 - 330
publisher
Springer
external identifiers
  • scopus:85032963825
  • pmid:29098321
ISSN
0012-186X
DOI
10.1007/s00125-017-4475-0
language
English
LU publication?
yes
id
d26e758b-cc13-4037-8ca0-c0e08ab5fdc1
date added to LUP
2017-11-22 12:11:53
date last changed
2025-04-04 15:26:50
@article{d26e758b-cc13-4037-8ca0-c0e08ab5fdc1,
  abstract     = {{<p>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 (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10<sup>−3</sup>) and higher fasting insulin (0.030 ± 0.005 [log<sub>e</sub> pmol/l], p = 2.0 × 10<sup>−10</sup>). 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 β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 log<sub>e</sub> 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.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).</p>}},
  author       = {{McKeown, Nicola M. and Dashti, Hassan S. and Ma, Jiantao and Haslam, Danielle E. and Kiefte-de Jong, Jessica C. and Smith, Caren E. and Tanaka, Toshiko and Graff, Mariaelisa and Lemaitre, Rozenn N. and Rybin, Denis and Sonestedt, Emily and Frazier-Wood, Alexis C. and Mook-Kanamori, Dennis O. and Li, Yanping and Wang, Carol A. and Leermakers, Elisabeth T.M. and Mikkilä, Vera and Young, Kristin L. and Mukamal, Kenneth J. and Cupples, L. Adrienne and Schulz, Christina Alexandra and Chen, Tzu An and Li-Gao, Ruifang and Huang, Tao and Oddy, Wendy H. and Raitakari, Olli and Rice, Kenneth and Meigs, James B. and Ericson, Ulrika and Steffen, Lyn M. and Rosendaal, Frits R. and Hofman, Albert and Kähönen, Mika and Psaty, Bruce M. and Brunkwall, Louise and Uitterlinden, Andre G. and Viikari, Jorma and Siscovick, David S. and Seppälä, Ilkka and North, Kari E. and Mozaffarian, Dariush and Dupuis, Josée and Orho-Melander, Marju and Rich, Stephen S. and de Mutsert, Renée and Qi, Lu and Pennell, Craig E. and Franco, Oscar H. and Lehtimäki, Terho and Herman, Mark A.}},
  issn         = {{0012-186X}},
  keywords     = {{Carbohydrate metabolism; Epidemiology; Genetics; Meta-analysis; Nutrition; Type 2 diabetes}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{317--330}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1007/s00125-017-4475-0}},
  doi          = {{10.1007/s00125-017-4475-0}},
  volume       = {{61}},
  year         = {{2018}},
}