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02.11.2017 | Article

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

verfasst von: Nicola M. McKeown, Hassan S. Dashti, Jiantao Ma, Danielle E. Haslam, Jessica C. Kiefte-de Jong, Caren E. Smith, Toshiko Tanaka, Mariaelisa Graff, Rozenn N. Lemaitre, Denis Rybin, Emily Sonestedt, Alexis C. Frazier-Wood, Dennis O. Mook-Kanamori, Yanping Li, Carol A. Wang, Elisabeth T. M. Leermakers, Vera Mikkilä, Kristin L. Young, Kenneth J. Mukamal, L. Adrienne Cupples, Christina-Alexandra Schulz, Tzu-An Chen, Ruifang Li-Gao, Tao Huang, Wendy H. Oddy, Olli Raitakari, Kenneth Rice, James B. Meigs, Ulrika Ericson, Lyn M. Steffen, Frits R. Rosendaal, Albert Hofman, Mika Kähönen, Bruce M. Psaty, Louise Brunkwall, Andre G. Uitterlinden, Jorma Viikari, David S. Siscovick, Ilkka Seppälä, Kari E. North, Dariush Mozaffarian, Josée Dupuis, Marju Orho-Melander, Stephen S. Rich, Renée de Mutsert, Lu Qi, Craig E. Pennell, Oscar H. Franco, Terho Lehtimäki, Mark A. Herman

Erschienen in: Diabetologia | Ausgabe 2/2018

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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 (β ± 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 β-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).

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Titel: 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
verfasst von: Nicola M. McKeown
Hassan S. Dashti
Jiantao Ma
Danielle E. Haslam
Jessica C. Kiefte-de Jong
Caren E. Smith
Toshiko Tanaka
Mariaelisa Graff
Rozenn N. Lemaitre
Denis Rybin
Emily Sonestedt
Alexis C. Frazier-Wood
Dennis O. Mook-Kanamori
Yanping Li
Carol A. Wang
Elisabeth T. M. Leermakers
Vera Mikkilä
Kristin L. Young
Kenneth J. Mukamal
L. Adrienne Cupples
Christina-Alexandra Schulz
Tzu-An Chen
Ruifang Li-Gao
Tao Huang
Wendy H. Oddy
Olli Raitakari
Kenneth Rice
James B. Meigs
Ulrika Ericson
Lyn M. Steffen
Frits R. Rosendaal
Albert Hofman
Mika Kähönen
Bruce M. Psaty
Louise Brunkwall
Andre G. Uitterlinden
Jorma Viikari
David S. Siscovick
Ilkka Seppälä
Kari E. North
Dariush Mozaffarian
Josée Dupuis
Marju Orho-Melander
Stephen S. Rich
Renée de Mutsert
Lu Qi
Craig E. Pennell
Oscar H. Franco
Terho Lehtimäki
Mark A. Herman
Publikationsdatum: 02.11.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 2/2018
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-017-4475-0

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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