Mealtime media use and cardiometabolic risk in children.

OBJECTIVES: To examine the association between mealtime media use and non-HDL-cholesterol as well as other markers of cardiometabolic risk (CMR) in children. DESIGN: A repeated measures study design was used to examine the association between mealtime media use and CMR outcomes. Multivariable linear regression with generalised estimating equations was used to examine the association between mealtime media use and CMR outcomes. Analyses were stratified a priori by age groups (1-4 and 5-13 years). SETTING: The TARGet Kids! Practice-based research network in Toronto, Canada. PARTICIPANTS: 2117 children aged 1-13 years were included in the analysis. RESULTS: After adjusting for covariates, there was no evidence that total mealtime media use was associated with non-HDL-cholesterol in 1-4 year olds (P = 0·10) or 5-13 year olds (P = 0·29). Each additional meal with media per week was associated with decreased HDL-cholesterol in 5-13 year olds (-0·006 mmol/l; 95 % CI -0·009, -0·002; P = 0·003) and log-TAG in 1-4 year olds (ß = -0·004; 95 % CI -0·008, -0·00009; P = 0·04). Media use during breakfast was associated with decreased HDL-cholesterol in 5-13 year olds (-0·012 mmol/l; 95 % CI -0·02, -0·004; P = 0·002), while media during lunch was associated with decreased log-TAG (-0·01 mmol/l; 95 % CI -0·03, -0·002; P = 0·03) in children aged 1-4 years. Total mealtime media use was not associated with total cholesterol, glucose or insulin in either age group. CONCLUSIONS: Mealtime media use may be associated with unfavourable lipid profiles through effects on HDL-cholesterol in school-aged children but likely not in pre-schoolers.

Sugar-containing beverage consumption and cardiometabolic risk in preschool children.

OBJECTIVE: Sugar-containing beverages (SCBs) including 100% fruit juice, fruit drinks and soda substantially contribute to total caloric intake in young children. The objective of this study was to examine whether consumption of SCB is associated with cardiometabolic risk (CMR) in preschool children, along with whether 100% fruit juice and sugar sweetened beverage (SSB) is associated with CMR. STUDY DESIGN: We used a repeated measures study design examining SCB consumption and CMR outcomes measured concurrently in children 3-6 years of age participating in TARGet Kids!, a primary-care, practice-based research network in Canada (2008-2017). To account for within-person variability, multivariable linear regression models using generalized estimating equation was used to examine the association between SCB consumption and CMR score and the individual CMR score components including systolic blood pressure, waist circumference, high-density lipoprotein cholesterol (HDL-c), triglycerides, and glucose. RESULTS: After adjusting for sociodemographic, familial and child-related covariates, higher SCB consumption was associated with elevated CMR score [0.05 (95% CI -0.0001 to 0.09), p = 0.05], including lower HDL-c [-0.02 mmol/L (95% CI -0.03 to -0.01), p = 0.01] and higher triglycerides [0.02 mmol/L (95% CI 0.004 to 0.04), p = 0.02]. When examined separately, higher 100% fruit juice [-0.02 mmol/L (95% CI -0.03 to -0.003), p = 0.02] and SSB[-0.03 mmol/L (95% CI -0.06 to -0.001), p = 0.04] consumption were each associated with lower HDL-c. CONCLUSION: Higher SCB consumption was associated with small elevations of CMR in preschool children. Our findings support recommendations to limit overall intake of SCBs in early childhood, in effort to reduce the potential long-term burden of CMR.

Association of accelerated body mass index gain with repeated measures of blood pressure in early childhood.

BACKGROUND/OBJECTIVES: We examined the association for rates of age- and sex-standardized body mass index (zBMI) gain between 0-3, 3-18, and 18-36 months with BP in children at 36-72 months of age. METHODS: We collected repeated measures of zBMI and BP in 2502 children. zBMI was calculated using the World Health Organization standards. Each child's zBMI at birth and rates of zBMI gain in each period from birth to 36 months were estimated using linear spline multilevel models. Generalized estimating equations were used to determine whether zBMI at birth and zBMI gain between 0-3, 3-18, and 18-36 months were each associated with repeated measures of BP at 36-72 months of age. We sequentially conditioned on zBMI at birth and zBMI gain in each period prior to each period tested, as covariates, and adjusted for important socio-demographic, familial, and study design covariates. We examined whether these associations were modified by birthweight or maternal obesity, by including interaction terms. RESULTS: After adjusting for all covariates and conditioning on prior zBMI gains, a 1 standard deviation unit faster rate of zBMI gain during 0-3 months, (ß = 0.59 mmHg; 95% CI 0.31, 0.86) and 3-18 months (ß = 0.74 mmHg; 95% CI 0.46, 1.03) were each associated with higher systolic BP at 36-72 months. No significant associations were observed, however, for zBMI at birth or zBMI gain in the 18-36 month growth period. zBMI gains from 0-3 and 3-18 months were also associated with diastolic BP. Birthweight significantly modified the relationship during the 3-18 month period (p = 0.02), with the low birthweight group exhibiting the strongest association for faster rate of zBMI gain with higher systolic BP (ß = 1.31 mmHg; 95% CI 0.14, 2.48). CONCLUSIONS: Given that long-term exposure to small elevations in BP are associated with subclinical cardiovascular disease, promoting interventions targeting healthy growth in infancy may be important.

Breastfeeding duration, maternal body mass index, and birth weight are associated with differences in body mass index growth trajectories in early childhood.

Background: Accelerated postnatal growth is an important predictor for obesity risk. It is unknown whether early-life obesity-related risk factors affect body mass index (BMI) growth rates during distinct growth periods from early infancy through preschool years. Objective: We examined whether breastfeeding duration, maternal BMI, and birth weight are associated with growth trajectories of age- and sex-standardized WHO BMI z scores (zBMIs) in young children. Design: Children (n = 5905) in The Applied Research Group for Kids (TARGet Kids!) prospective cohort study underwent repeated measures of weight and length or height from birth to 10 y of age. Piecewise linear mixed models were used to determine whether zBMI growth rates differ for each risk factor during periods of growth between birth and 1, 3, 18, 36, and 72 mo of age. Results: Children who were breastfed <6 mo compared with ≥6 mo showed a higher growth rate between 1-3 and 3-18 mo, resulting in higher standardized BMIs (zBMIs) of +0.24, +0.12, and +0.19 at 18, 36, and 72 mo, respectively. Maternal BMI (in kg/m2) ≥30 compared with <30 resulted in higher growth rates between 1-3 and 36-72 mo and higher zBMIs of +0.22, +0.14, +0.18, and +0.41 at 3, 18, 36, and 72 mo, respectively. Infants weighing <2.5 kg at birth (compared with 2.5-4 kg) experienced higher growth rates between 1-3 and 3-18 mo but had lower zBMIs at all time points (zBMI: -1.45 to -0.21). Infants weighing ≥4 kg at birth (compared with 2.5-4 kg) had significantly lower growth rates in the first 3 mo but higher zBMIs at all time points (zBMI: +1.16 to +0.27). Conclusion: Differences in zBMI growth rates by breastfeeding duration, maternal BMI, and birth weight are seen in early infancy and contribute to differences in zBMI, which persist into midchildhood. This trial was registered at www.clinicaltrials.gov as NCT01869530.

Genetic Variants Associated with Circulating Parathyroid Hormone.

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10-17), rs219779 adjacent to CLDN14 (P=3.5 × 10-16), rs4443100 near RTDR1 (P=8.7 × 10-9), and rs73186030 near CASR (P=4.8 × 10-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars.

BACKGROUND/AIMS: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. METHODS: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. RESULTS: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004). CONCLUSION: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.

Caffeine Consumption Contributes to Skin Intrinsic Fluorescence in Type 1 Diabetes.

BACKGROUND: A variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine. MATERIALS AND METHODS: SIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and SIF14 (456-nm LED). Food frequency questionnaires were used to estimate mean caffeine intake. To establish replication, we examined a second type 1 diabetes cohort. RESULTS: Higher caffeine intake was significantly associated with higher SIF1(LED 375 nm[0.6, 0.2]) (P=2×10(-32)) and SIF14L(ED 456 nm[0.4, 0.8]) (P=7×10(-31)) and accounted for 4% of the variance in each after adjusting for covariates. When analyzed together, caffeine intake and rs1495741 both remained highly significantly associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]). Mean caffeinated coffee intake was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) (P=9×10(-12)) and SIF14(LED 456 nm[0.4, 0.8]) (P=4×10(-12)), but no association was observed for decaffeinated coffee intake. Finally, caffeine was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]) (P<0.0001) in the replication cohort. CONCLUSIONS: Caffeine contributes to SIF. The effect of rs1495741 on SIF appears to be partially independent of caffeine consumption. Because SIF and coffee intake are each associated with cardiovascular disease, our findings suggest that accounting for coffee and/or caffeine intake may improve risk prediction models for SIF and cardiovascular disease in individuals with diabetes.

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence.

AIMS/HYPOTHESIS: Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts. METHODS: Cohort 1 included 1,082 participants, 35-67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18-90 years. RESULTS: rs1495741 was significantly associated with SF in Cohort 1 (p < 6 × 10(-10)), which is known to tag the NAT2 acetylator phenotype. The fast acetylator genotype was associated with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal associated with SF (p = 8.3 × 10(-42)) was rs4921914, also in NAT2, 440 bases upstream of rs1495741 (linkage disequilibrium r (2) = 1.0 for rs4921914 with rs1495741). We replicated these results in two additional cohorts, one with and one without type 1 diabetes. Finally, to understand which compounds are contributing to the NAT2-SF signal, we examined 11 compounds assayed from skin biopsies (n = 198): the fast acetylator genotype was associated with lower levels of the AGEs hydroimidazolones of glyoxal (p = 0.017). CONCLUSIONS/INTERPRETATION: We identified a robust association between NAT2 and SF in people with and without diabetes. Our findings provide proof of principle that genetic variation contributes to interindividual SF and that NAT2 acetylation status plays a major role.

Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations.

BACKGROUND: Taste is an important determinant of food consumption, and genetic variations in the sweet taste receptor subunit TAS1R2 may contribute to interindividual variations in sugar consumption. OBJECTIVE: We determined whether Ser9Cys and Ile191Val variations in TAS1R2 were associated with differences in the consumption of sugars in 2 populations. DESIGN: Population 1 included 1037 diabetes-free young adults in whom we assessed dietary intake by using a 1-mo, 196-item food-frequency questionnaire. Population 2 consisted of 100 individuals with type 2 diabetes with dietary intakes assessed by using 2 sets of 3-d food records administered 2 wk apart. Dietary counseling was provided between food records 1 and 2. Dietary intakes between genotypes were compared by using analysis of covariance adjusted for potential confounders. RESULTS: In population 1, a significant Ile191Val × body mass index (BMI; in kg/m²) interaction was detected for the consumption of sugars, and the effect of genotype was significant only in individuals with a BMI ≥ 25 (n = 205). In comparison with individuals homozygous for the Ile allele, Val carriers consumed fewer sugars (122 ± 6 compared with 103 ± 6 g sugar/d, respectively; P = 0.01). Regression estimates that associated BMI with total sugar consumption by Ile/Ile and Val-carrier genotype intersected at a BMI of 23.5. In population 2, Val carriers also consumed less sugar than did individuals with the Ile/Ile genotype (99 ± 6 compared with 83 ± 6 g sugar/d, respectively; P = 0.04) on food record 2, and sugar was the only macronutrient that decreased significantly (-9 ± 4 g sugar/d, P = 0.02) in Val carriers who received dietary counseling. CONCLUSION: Our findings show that a genetic variation in TAS1R2 affects habitual consumption of sugars and may contribute to interindividual differences in changing behaviors in response to dietary counseling.

Comparison of body mass index and waist circumference as predictors of cardiometabolic health in a population of young Canadian adults.

BACKGROUND: This study aimed to investigate whether waist circumference (WC) or body mass index (BMI) is a better predictor of blood lipid concentrations among young men and women from different ethnocultural groups. METHODS: Participants were 1181 healthy men (n = 358) and women (n = 823) aged 20-29 years taken from the cross-sectional Toronto Nutrigenomics and Health Study. Analyses were conducted separately for men and women, and for Caucasian and East Asian ethnocultural groups. Serum triglycerides (TG) and total to HDL cholesterol ratio (TC:HDL cholesterol) were used as outcomes. Associations between the adiposity and blood lipid measures were examined using partial correlations and odds ratios derived from logistic regression models. RESULTS: WC had a stronger association with serum lipid concentrations than BMI. WC was significantly related to TG and TC:HDL cholesterol after adjusting for BMI and covariates among men and women (P

Genetic variation in taste and its influence on food selection.

Abstract Taste perception plays a key role in determining individual food preferences and dietary habits. Individual differences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutritional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is growing evidence that "fat taste" may represent a sixth modality. Several taste receptors have been identified within taste cell membranes on the surface of the tongue, and they include the T2R family of bitter taste receptors, the T1R receptors associated with sweet and umami taste perception, the ion channels PKD1L3 and PKD2L1 linked to sour taste, and the integral membrane protein CD36, which is a putative "fat taste" receptor. Additionally, epithelial sodium channels and a vanilloid receptor, TRPV1, may account for salty taste perception. Common polymorphisms in genes involved in taste perception may account for some of the interindividual differences in food preferences and dietary habits within and between populations. This variability could affect food choices and dietary habits, which may influence nutritional and health status and the risk of chronic disease. This review will summarize the present state of knowledge of the genetic variation in taste, and how such variation might influence food intake behaviors.

Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free-living population of men and women.

BACKGROUND/AIMS: The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. METHODS: Caucasian men (n = 96) and women (n = 217) 20-29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. RESULTS: Among men, consumption of sucrose was 60 +/- 6, 48 +/- 4, and 39 +/- 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 +/- 4, 53 +/- 2, and 44 +/- 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. CONCLUSIONS: These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption.

Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations.

Glucose sensing in the brain has been proposed to be involved in regulating food intake, but the mechanism is not known. Glucose transporter type 2 (GLUT2)-null mice fail to control their food intake in response to glucose, suggesting a potential role for this transporter as a glucose sensor in the brain. Here we show that individuals with a genetic variation in GLUT2 (Thr110Ile) have a higher daily intake of sugars in two distinct populations. In the first population, compared with individuals with the Thr/Thr genotype, carriers of the Ile allele had a significantly higher intake of sugars as assessed from 3-day food records administered on two separate visits (visit 1: 112 +/- 9 vs. 86 +/- 4 g/day, P = 0.01; visit 2: 111 +/- 8 vs. 82 +/- 4 g/day, P = 0.003), demonstrating within-population reproducibility. In a second population, carriers of the Ile allele also reported consuming a significantly greater intake of sugars (131 +/- 5 vs. 115 +/- 3 g/day, P = 0.007) over a 1-mo period as measured from a food frequency questionnaire. GLUT2 genotypes were not associated with fat, protein, or alcohol intake in either population. These observations were consistent across older and younger adults as well as among subjects with early Type 2 diabetes and healthy individuals. Taken together, our findings show that a genetic variation in GLUT2 is associated with habitual consumption of sugars, suggesting an underlying glucose-sensing mechanism that regulates food intake.