Anders Grøntved

Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis.

CONTEXT Prolonged television (TV) viewing is the most prevalent and pervasive sedentary behavior in industrialized countries and has been associated with morbidity and mortality. However, a systematic and quantitative assessment of published studies is not available. OBJECTIVE To perform a meta-analysis of all prospective cohort studies to determine the association between TV viewing and risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. DATA SOURCES AND STUDY SELECTION Relevant studies were identified by searches of the MEDLINE database from 1970 to March 2011 and the EMBASE database from 1974 to March 2011 without restrictions and by reviewing reference lists from retrieved articles. Cohort studies that reported relative risk estimates with 95% confidence intervals (CIs) for the associations of interest were included. DATA EXTRACTION Data were extracted independently by each author and summary estimates of association were obtained using a random-effects model. DATA SYNTHESIS Of the 8 studies included, 4 reported results on type 2 diabetes (175,938 individuals; 6428 incident cases during 1.1 million person-years of follow-up), 4 reported on fatal or nonfatal cardiovascular disease (34,253 individuals; 1052 incident cases), and 3 reported on all-cause mortality (26,509 individuals; 1879 deaths during 202,353 person-years of follow-up). The pooled relative risks per 2 hours of TV viewing per day were 1.20 (95% CI, 1.14-1.27) for type 2 diabetes, 1.15 (95% CI, 1.06-1.23) for fatal or nonfatal cardiovascular disease, and 1.13 (95% CI, 1.07-1.18) for all-cause mortality. While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day. The estimated absolute risk differences per every 2 hours of TV viewing per day were 176 cases of type 2 diabetes per 100,000 individuals per year, 38 cases of fatal cardiovascular disease per 100,000 individuals per year, and 104 deaths for all-cause mortality per 100,000 individuals per year. CONCLUSION Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality.

Genetic susceptibility to obesity and related traits in childhood and adolescence; influence of loci identified by genome-wide association studies

OBJECTIVE Large-scale genome-wide association (GWA) studies have thus far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children and adolescents. RESEARCH DESIGN AND METHODS Seventeen variants representing 16 obesity susceptibility loci were genotyped in 1,252 children (mean ± SD age 9.7 ± 0.4 years) and 790 adolescents (15.5 ± 0.5 years) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by summing the number of effect alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analyzed with previously reported data (Ntotal = 13,071 children and adolescents). RESULTS In EYHS, 15 variants showed associations or trends with anthropometric traits that were directionally consistent with earlier reports in adults. The meta-analysis showed directionally consistent associations with BMI for all 13 variants, of which 9 were significant (0.033–0.098 SD/allele; P < 0.05). The near-TMEM18 variant had the strongest effect (0.098 SD/allele P = 8.5 × 10−11). Effect sizes for BMI tended to be more pronounced in children and adolescents than reported earlier in adults for variants in or near SEC16B, TMEM18, and KCTD15, (0.028–0.035 SD/allele higher) and less pronounced for rs925946 in BDNF (0.028 SD/allele lower). Each additional effect allele in the GPS-17 was associated with an increase of 0.034 SD in BMI (P = 3.6 × 10−5), 0.039 SD, in sum of skinfolds (P = 1.7 × 10−7), and 0.022 SD in waist circumference (P = 1.7 × 10−4), which is comparable with reported results in adults (0.039 SD/allele for BMI and 0.033 SD/allele for waist circumference). CONCLUSIONS Most obesity susceptibility loci identified by GWA studies in adults are already associated with anthropometric traits in children/adolescents. Whereas the association of some variants may differ with age, the cumulative effect size is similar.

Association of Genetic Loci With Glucose Levels in Childhood and Adolescence: A Meta-Analysis of Over 6,000 Children

OBJECTIVE To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9–16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021–0.031) for each unit increase in the score. CONCLUSIONS Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.

Association of genetic Loci with glucose levels in childhood and adolescence

OBJECTIVE To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9–16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021–0.031) for each unit increase in the score. CONCLUSIONS Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.

Youth screen-time behaviour is associated with cardiovascular risk in young adulthood: the European Youth Heart Study

Aims: We prospectively examined the association of TV viewing, computer use, and total screen time in adolescence, and change in these behaviours, with cardiovascular disease (CVD) risk factors in young adulthood. Methods and results: This was a prospective cohort study among Danish men and women (n = 435) followed for up to 12 years. Adiposity, blood pressure (BP), triglycerides, high-density lipoprotein (HDL), glucose, insulin, and self-reported TV viewing and computer use were obtained in adolescence and in young adulthood. A continuous metabolic syndrome z-score was calculated as the sum of standardized values of each risk factor (inverse of HDL). In multivariable-adjusted analyses, TV viewing and total screen time in adolescence were positively associated with adiposity, triglycerides, and metabolic syndrome z-score in young adulthood (p < 0.05). Individuals who increased their TV viewing, computer use, or total screen time with more than 2 hours/day from adolescence to young adulthood had 0.90 (95% CI 0.12 to 1.69), 0.95 (95% CI 0.01 to 1.88), and 1.40 (95% CI 0.28 to 2.51) kg/m2 higher body mass index, respectively, in young adulthood compared with individuals who remained stable or decreased their viewing time. Insulin and metabolic syndrome z-scores were also higher among individuals who increased their TV viewing, computer use, or total screen time more than 2 hours/day compared with individuals who remained stable or decreased their viewing time (p < 0.05). Conclusions: Prolonged TV viewing and total screen time during leisure time in adolescence, and increases in these behaviours, are associated with unfavourable levels of several cardiovascular risk factors in young adulthood.

Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals

BACKGROUND High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. OBJECTIVE The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. DESIGN A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837). RESULTS Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. CONCLUSIONS Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

A comparison between BMI, waist circumference, and waist-to-height ratio for identifying cardio-metabolic risk in children and adolescents

Background There is controversial evidence on the associations between anthropometric measures with clustering of cardiovascular disease risk factors in pediatric ages. We aimed to examine the associations between body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with clustered cardiometabolic risk factors and to determine whether these anthropometric variables can be used to discriminate individuals with increased cardiometabolic risk (increased clustered triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, and HOMA-IR). Methods The study sample of 4255 (2191 girls and 2064 boys) participants (8–17 years) was derived from pooled cross-sectional data comprising five studies. Outcomes included a continuous cardiometabolic risk factor z-score [corresponding to the sum of z-scores for triglycerides, HDL-cholesterol, systolic and diastolic blood pressure (mean arterial pressure), and HOMA-IR] and children with ≥1.0 SD in this score were defined as being at risk for clustering cardiometabolic risk factors.. Exposure variables were BMI, WC, WHtR. Statistics included mixed-effect regression and ROC analysis. Results All anthropometric variables were associated with clustered risk and the magnitudes of associations were similar for BMI, WC, and WHtR. Models including anthropometric variables were similar in discriminating children and adolescents at increased risk with areas under the ROC curve between 0.70 and 0.74. The sensitivity (boys: 80.5–86.4%; girls: 76.6–82.3%) was markedly higher than specificity (boys: 51.85–59.4%; girls: 60.8%). Conclusions The magnitude of associations for BMI, WC, and WHtR are similar in relation to clustered cardiometabolic risk factors, and perform better at higher levels of BMI. However, the precision of these anthropometric variables to classify increased risk is low.

Sugar-sweetened beverages consumption in relation to changes in body fatness over 6 and 12 years among 9-year-old children: the European Youth Heart Study

Background/Objectives:In parallel with the obesity epidemic, consumption of sugar-sweetened beverages (SSB) has risen over the same period. Our aim was to investigate associations between the consumption of SSB in childhood and adolescence with subsequent changes in body fatness in early adulthood.Subjects/Methods:A longitudinal study of 9-year-old children (n=283) enrolled in the Danish part of the European Youth Heart Study with a 6-year and 12-year follow-up. Data were collected at ages 9, 15 and 21 years. Multivariate regression analyses with adjustment for potential confounders were used to evaluate the effect of SSB consumption at 9 and 15 years and change in SSB consumption from 9–15 years on subsequent change in body fatness until 21 years.Results:Subjects who consumed more than one serve of SSB daily at age 15 years had larger increases in body mass index (BMI) (β=0.92, P=0.046) and waist circumference (WC) (β=2.69, P=0.04) compared to non-consumers over the subsequent 6 years. In addition, subjects who increased their SSB consumption from age 9–15 years also had larger increases in BMI (β=0.91, P=0.09) and WC (β=2.72, P=0.04) from 15–21 years, compared to those who reported no change in consumption. No significant association was observed from 9–21 years.Conclusion:This study provides new evidence that SSB consumption in adolescence and changes in SSB consumption from childhood to adolescence are both significant predictors of change in body fatness later in early adulthood.

A new approach to define and diagnose cardiometabolic disorder in children

The aim of the study was to test the performance of a new definition of metabolic syndrome (MetS), which better describes metabolic dysfunction in children. Methods. 15,794 youths aged 6–18 years participated. Mean z-score for CVD risk factors was calculated. Sensitivity analyses were performed to evaluate which parameters best described the metabolic dysfunction by analysing the score against independent variables not included in the score. Results. More youth had clustering of CVD risk factors (>6.2%) compared to the number selected by existing MetS definitions (International Diabetes Federation (IDF) < 1%). Waist circumference and BMI were interchangeable, but using insulin resistance homeostasis model assessment (HOMA) instead of fasting glucose increased the score. The continuous MetS score was increased when cardiorespiratory fitness (CRF) and leptin were included. A mean z-score of 0.40–0.85 indicated borderline and above 0.85 indicated clustering of risk factors. A noninvasive risk score based on adiposity and CRF showed sensitivity and specificity of 0.85 and an area under the curve of 0.92 against IDF definition of MetS. Conclusions. Diagnosis for MetS in youth can be improved by using continuous variables for risk factors and by including CRF and leptin.

Muscle strength in youth and cardiovascular risk in young adulthood (the European Youth Heart Study)

Background Whether muscle strength in youth is related to cardiovascular risk later in life independent of cardiorespiratory fitness is unclear. Methods We examined the independent association of isometric muscle strength in youth with cardiovascular risk factors in young adulthood using data from the Danish European Youth Heart Study; a population-based prospective cohort study among boys and girls (n=332) followed for up to 12 years. In youth maximal voluntary contractions during isometric back extension and abdominal flexion were determined using a strain-gauge dynamometer and cardiorespiratory fitness was obtained from a maximal cycle ergometer test. Cardiovascular risk factors were obtained in youth and in young adulthood. Associations were examined using multivariable-adjusted regression models including major confounding factors. Results Each 1 SD difference in isometric muscle strength in youth (0.17 N/kg) was inversely associated with body mass index (BMI; −0.60 kg/m2, 95% CI −0.97 to −0.22), triglyceride (−0.09 mmol/l, 95% CI −0.16 to −0.02), diastolic blood pressure (BP) (−1.22 mm Hg, 95% CI −2.15 to −0.29) and a composite cardiovascular risk factor score (−0.61 SD, 95% CI −1.03 to −0.20) in young adulthood in multivariable-adjusted analyses including fitness. Associations to triglyceride, diastolic BP and the cardiovascular risk factor score remained with additional adjustment for waist circumference or BMI. Each 1 SD difference in isometric muscle strength in youth was significantly associated with 0.59 (95% CI 0.40 to 0.87) lower odds of general overweight/obesity in young adulthood (p=0.007) and was marginally associated with incident raised BP, raised triglyceride and low high-density lipoprotein cholesterol. Conclusions This study suggests that greater isometric muscle strength in youth is associated with lower levels of cardiovascular risk factors in young adulthood independent of fitness, adiposity and other confounding factors.