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

Authors: MCKEOWN, NICOLA - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; DASHTI, HASSAN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; MA, JIANTAO - FRAMINGHAM HEART STUDY; HASLAM, DANIELLE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; KIEFTE-DE JONG, JESSICA - ERASMUS MEDICAL CENTER; SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; TANAKA, TOSHIKO - NATIONAL INSTITUTE ON AGING (NIA, NIH); GRAFF, MARIAELISA - UNIVERSITY OF NORTH CAROLINA; LEMAITRE, ROZENN - UNIVERSITY OF WASHINGTON; RYBIN, DENIS - BOSTON UNIVERSITY; SONESTEDT, EMILY - LUND UNIVERSITY; FRAZIER-WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); MOOK-KANAMORI, DENNIS - LEIDEN UNIVERSITY MEDICAL CENTER; LI, YANPING - HARVARD SCHOOL OF PUBLIC HEALTH; WANG, CAROL - UNIVERSITY OF WESTERN AUSTRALIA

Submitted to: Diabetologia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2017
Publication Date: 11/2/2017
Citation: McKeown, N.M., Dashti, H.S., Ma, J., Haslam, D.E., Kiefte-de Jong, J.C., Smith, C.E., Tanaka, T., Graff, M., Lemaitre, R.N., Rybin, D., Sonestedt, E., Frazier-Wood, A.C., Mook-Kanamori, D.O., Li, Y., Wang, C.A., Leermakers, E.T.M., Mikkila, V., Young, K.L., Mukamal, K.J., Cupples, L.A., Schulz, C.A., Chen, T.A., Li-Gao, R., Huang, T., Oddy, W.H., Raitakari, O., Rice, K., Meigs, J.B., Ericson, U., Steffen, L.M., Rosendaal, F.R., Hofman, A., Kahonen, M., Psaty, B.M., Brunkwall, L., Uitterlinden, A.G., Viikari, J., Siscovick, D.S., Seppala, I., North, K.E., Mozaffarian, D., Dupuis, J., Orho-Melander, M., Rich, S.S., de Mutsert, R., Qi, L., Pennell, C.E., Franco, O.H., Lehtimaki, T., Herman, M.A. 2017. 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. Diabetologia. https://doi.org/10.1007/s00125-017-4475-0.

Interpretive Summary: Drinks with added sugar, such as non-diet soda, contain a lot of fructose. Fructose has been associated with poorer blood sugar control which in turn puts individuals at risk of diabetes, but data suggest that that the association between fructose intake and diabetes risk is only true for some people. The problem is that we do not know who has altered blood sugar control in response to consuming fructose, and so it is hard to advise people on the extent to which they should personally limit their intake of drinks with added sugar. To address this problem, we aimed to see whether genetic variation in 11 genes involved in fructose metabolism pathways altered the association between measures of blood sugar control and intake of drinks with added sugars. We included data from nearly 35,000 adults and assessed their intake of sodas, fruit punches, lemonades, or other fruit drinks by questionnaire or food diaries. We measured their fasting levels of glucose and insulin in the blood as a measure of blood glucose control, and we also ascertained their genetic variation in 11 genes involved in fructose metabolism. We found that intake of drinks with added sugar was associated with higher fasting glucose and higher fasting insulin, and that this association did not differ based on genetic differences in the 11 genes we assessed. This result suggests that consuming drinks with added sugar contributes to poorer blood sugar control, and we were unable to give data that might help identify individuals for whom this was not true. Therefore, this result confirms current dietary guidelines which advise that all individuals should limit their intake of drinks with added sugar. The information from this study will be helpful for developing dietary guidelines for the prevention of diabetes, and for healthcare practitioners who need to advise patients on the best diet for health.

Technical Abstract: 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. 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. 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 (B +/- 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 B-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. 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.