TY - JOUR
T1 - Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway
T2 - a meta-analysis
AU - McKeown, Nicola M.
AU - Dashti, Hassan S.
AU - Ma, Jiantao
AU - Haslam, Danielle E.
AU - Kiefte-de Jong, Jessica C.
AU - Smith, Caren E.
AU - Tanaka, Toshiko
AU - Graff, Mariaelisa
AU - Lemaitre, Rozenn N.
AU - Rybin, Denis
AU - Sonestedt, Emily
AU - Frazier-Wood, Alexis C.
AU - Mook-Kanamori, Dennis O.
AU - Li, Yanping
AU - Wang, Carol A.
AU - Leermakers, Elisabeth T.M.
AU - Mikkilä, Vera
AU - Young, Kristin L.
AU - Mukamal, Kenneth J.
AU - Cupples, L. Adrienne
AU - Schulz, Christina Alexandra
AU - Chen, Tzu An
AU - Li-Gao, Ruifang
AU - Huang, Tao
AU - Oddy, Wendy H.
AU - Raitakari, Olli
AU - Rice, Kenneth
AU - Meigs, James B.
AU - Ericson, Ulrika
AU - Steffen, Lyn M.
AU - Rosendaal, Frits R.
AU - Hofman, Albert
AU - Kähönen, Mika
AU - Psaty, Bruce M.
AU - Brunkwall, Louise
AU - Uitterlinden, Andre G.
AU - Viikari, Jorma
AU - Siscovick, David S.
AU - Seppälä, Ilkka
AU - North, Kari E.
AU - Mozaffarian, Dariush
AU - Dupuis, Josée
AU - Orho-Melander, Marju
AU - Rich, Stephen S.
AU - de Mutsert, Renée
AU - Qi, Lu
AU - Pennell, Craig E.
AU - Franco, Oscar H.
AU - Lehtimäki, Terho
AU - Herman, Mark A.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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).
AB - 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).
KW - Carbohydrate metabolism
KW - Epidemiology
KW - Genetics
KW - Meta-analysis
KW - Nutrition
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85032963825&partnerID=8YFLogxK
U2 - 10.1007/s00125-017-4475-0
DO - 10.1007/s00125-017-4475-0
M3 - Article
C2 - 29098321
AN - SCOPUS:85032963825
SN - 0012-186X
VL - 61
SP - 317
EP - 330
JO - Diabetologia
JF - Diabetologia
IS - 2
ER -
