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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.

Tuesday,2018-01-16 18:24 America/Los_Angeles — ecterry
TitleSugar-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.
Publication TypeJournal Article
Year of Publication2018
AuthorsMcKeown, NM, Dashti, HS, Ma, J, Haslam, DE, de Jong, JCKiefte-, Smith, CE, Tanaka, T, Graff, M, Lemaitre, RN, Rybin, D, Sonestedt, E, Frazier-Wood, AC, Mook-Kanamori, DO, Li, Y, Wang, CA, Leermakers, ETM, Mikkilä, V, Young, KL, Mukamal, KJ, Cupples, AL, Schulz, C-A, Chen, T-A, Li-Gao, R, Huang, T, Oddy, WH, Raitakari, O, Rice, K, Meigs, JB, Ericson, U, Steffen, LM, Rosendaal, FR, Hofman, A, Kähönen, M, Psaty, BM, Brunkwall, L, Uitterlinden, AG, Viikari, J, Siscovick, DS, Seppälä, I, North, KE, Mozaffarian, D, Dupuis, J, Orho-Melander, M, Rich, SS, de Mutsert, R, Qi, L, Pennell, CE, Franco, OH, Lehtimäki, T, Herman, MA
JournalDiabetologia
Volume61
Issue2
Pagination317-330
Date Published2018 Feb
ISSN1432-0428
Abstract<p><b>AIMS/HYPOTHESIS: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS/INTERPRETATION: </b>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.</p><p><b>TRIAL REGISTRATION: </b>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).</p>
DOI10.1007/s00125-017-4475-0
Alternate JournalDiabetologia
PubMed ID29098321
Grant ListHHSN268201100008C / / National Heart, Lung, and Blood Institute / United States
R01HL087641 / / National Heart, Lung, and Blood Institute / United States
HHSN268201200036C / / National Heart, Lung, and Blood Institute / United States
N01-HC-95163 / / SNP Health Association Resources (SHARe) / United States
R01HL087652 / / National Heart, Lung, and Blood Institute / United States
916.14.023 / / Dutch Science Organization / United States
R01HL071051 / / National Heart, Lung, and Blood Institute / United States
UL1RR025005 / / National Institutes of Health / United States
N01HC85086 / / National Heart, Lung, and Blood Institute / United States
KL2TR001109 / / National Institutes of Health / United States
N01-HC-95167 / / SNP Health Association Resources (SHARe) / United States
HHSN268200800007C / / National Heart, Lung, and Blood Institute / United States
HHSN268201100007C / / National Heart, Lung, and Blood Institute / United States
58-1950-0-014 / / USDA Agriculture Research Service / United States
R01HL071205 / / National Heart, Lung, and Blood Institute / United States
N01HC85082 / / National Heart, Lung, and Blood Institute / United States
UM1 CA186107 / / National Institutes of Health / United States
R01HL59367 / / National Heart, Lung, and Blood Institute / United States
117787 / / Suomen Akatemia / United States
126925 / / Suomen Akatemia / United States
003209 / / National Health and Medical Research Council Of Australia / United States
N01HC85079 / / National Heart, Lung, and Blood Institute / United States
K08 HL112845 / / National Institutes of Health / United States
N01-HC-95161 / / SNP Health Association Resources (SHARe) / United States
N01HC55222 / / National Heart, Lung, and Blood Institute / United States
R01HL071250 / / National Heart, Lung, and Blood Institute / United States
134309 / / Suomen Akatemia / United States
DK091718 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
5K01DK082729-04 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
121584 / / Suomen Akatemia / United States
R01 CA49449 / / National Institutes of Health / United States
N01-HC-95166 / / SNP Health Association Resources (SHARe) / United States
2011036 / / United States-Israel Binational Science Foundation / United States
UL1TR000124 / / National Center for Advancing Translational Sciences / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01-DK100425 / / National Institutes of Health / United States
R01HL071259 / / National Heart, Lung, and Blood Institute / United States
HHSN268201100012C / / National Heart, Lung, and Blood Institute / United States
403981 / / National Health and Medical Research Council Of Australia / United States
R01HL105756 / / National Heart, Lung, and Blood Institute / United States
R01HL071251 / / National Heart, Lung, and Blood Institute / United States
N01HC25195 / / National Heart, Lung, and Blood Institute / United States
HHSN268201100005C / / National Heart, Lung, and Blood Institute / United States
N01-HC-95169 / / SNP Health Association Resources (SHARe) / United States
U01HL080295 / / National Heart, Lung, and Blood Institute / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
U01 DK078616 / DK / NIDDK NIH HHS / United States
DK063491 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
R01HL130114 / / National Heart, Lung, and Blood Institute / United States
N01HC85083 / / National Heart, Lung, and Blood Institute / United States
N01HC85080 / / National Heart, Lung, and Blood Institute / United States
K24DK080140 / / National Institutes of Health / United States
P30 DK057521 / DK / NIDDK NIH HHS / United States
MOP-82893 / / Canadian Institutes of Health Research / Canada
124282 / / Suomen Akatemia / United States
DK58845 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
N02-HL-6-4278 / / National Heart, Lung, and Blood Institute / United States
X51001 / / Kuopio, Tampere and Turku University Hospital Medical Funds / United States
R01HL071258 / / National Heart, Lung, and Blood Institute / United States
HHSN268201100011C / / National Heart, Lung, and Blood Institute / United States
DK100383 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
P30 DK057521 / / Boston Area Diabetes, Endocrinology Research Center Feasibility Program / United States
N01-HC-95165 / / SNP Health Association Resources (SHARe) / United States
R01HL071252 / / National Heart, Lung, and Blood Institute / United States
N01-HC-95164 / / SNP Health Association Resources (SHARe) / United States
HL034594 / / National Heart, Lung, and Blood Institute / United States
129378 / / Suomen Akatemia / United States
R01HL086694 / / National Heart, Lung, and Blood Institute / United States
HHSN268201100009C / / National Heart, Lung, and Blood Institute / United States
R01AG023629 / / National Institute on Aging / United States
HHSN268201100006C / / National Heart, Lung, and Blood Institute / United States
R01DK078616 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
N02HL64278 / / National Heart, Lung, and Blood Institute / United States
HHSN268201100010C / / National Heart, Lung, and Blood Institute / United States
N01-HC-95160 / / SNP Health Association Resources (SHARe) / United States
0730094N / / American Heart Association / United States
N01-HC-95159 / / SNP Health Association Resources (SHARe) / United States
HL071981 / / National Heart, Lung, and Blood Institute / United States
U01HG004402 / / National Human Genome Research Institute / United States
R01HL120393 / / National Heart, Lung, and Blood Institute / United States
N01HC85081 / / National Heart, Lung, and Blood Institute / United States
HL105756 / / National Heart, Lung, and Blood Institute / United States
R01HL103612 / / National Heart, Lung, and Blood Institute / United States
DK46200 / / Boston Obesity Nutrition Research Center / United States
RR-024156 / / National Heart, Lung, and Blood Institute / United States
U01DK078616 / / National Institutes of Health / United States
N01-HC-95168 / / SNP Health Association Resources (SHARe) / United States
41071 / / Suomen Akatemia / United States
N01-HC-95162 / / SNP Health Association Resources (SHARe) / United States
286284 / / Suomen Akatemia / United States
HL126024 / / National Heart, Lung, and Blood Institute / United States
ePub date: 
18/02

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