Constantina Papoutsakis

Association Between Family Divorce and Children's BMI and Meal Patterns: The GENDAI Study

The aim of this work was to explore the associations between family factors, including divorce, and childrens overweight as well as eating and physical activity patterns in a population‐based sample of healthy school‐aged children. In this cross‐sectional study, 1,138 children (53% girls; age: 11.2 ± 0.7 years) from elementary schools in the Attica region participated. Their parents provided sociodemographic information, including their marital status. Overweight status classification was based on weight and height measurements and BMI evaluation. Children completed a physical activity checklist and a questionnaire on meal patterns and eating behaviors. The Eating Style score was calculated: the higher the score, the more frequent a child was engaged in less‐structured feeding practices promoting food intake for reasons other than hunger. Analysis revealed significant association between family divorce and childrens overweight: compared with children of married parents, those of divorced had significantly higher BMI levels (20.0 ± 3.6 kg/m2 vs. 21.3 ± 3.4 kg/m2, respectively, P = 0.007). Controlling for socioeconomic and physical activity factors, divorce remains a significant predictor of a higher BMI, along with older age, higher fathers and mothers BMI, less children in the family, and more minutes of daily screen time. Children who had experienced a divorce in their family also reported higher Eating Style score, even after adjusting for potential confounders. In conclusion, in this sample of fifth and sixth graders, unfavorable family circumstances have been associated with childrens overweight, as well as with aspects of their eating behavior, namely eating style in relation to conditions around food consumption and hunger, independent of other socioeconomic factors.

Meta-Analysis Investigating Associations Between Healthy Diet and Fasting Glucose and Insulin Levels and Modification by Loci Associated With Glucose Homeostasis in Data From 15 Cohorts

Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 U.S. and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG (β = -0.004 mmol/L, 95% confidence interval: -0.005, -0.003) and FI (β = -0.008 ln-pmol/L, 95% confidence interval: -0.009, -0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

Disordered eating attitudes: An emerging health problem among Mediterranean adolescents

Aim of the present study was to investigate eating attitudes in a group of Mediterranean high school students. One hundred and twenty high school students participated in this survey. The Eating Attitudes Test (EAT-26) was used for evaluating symptoms and attitudes associated with disordered eating. Body composition and dietary intake were also assessed. Using the cut-off point of 20 in the total EAT, 13 females (20.3%) and 4 males (7.3%) exhibited disordered eating behavior. Overweight students had significantly higher scores in the dieting scale than those in the normal BMI range. Percent fat mass was positively related to the total EAT (r=0.326, p<0.001) and the dieting scale (r=0.489, p<0.001). Waist/hip ratio was negatively related to total EAT and its scales. In conclusion, a significant percentage of students in this urban Mediterranean adolescent population found to have abnormal eating attitudes. This finding may be partly explained by the effect of cultural transition.

Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation–derived criteria and associations with adiponectin and leptin

The aims of the study were to determine the prevalence of metabolic syndrome (MS) components and examine associations with adipokine concentrations in a healthy pediatric cohort. A cross-sectional study of 1138 children (53% girls; mean age of all participants, 11.2 ± 0.7 years) was performed. Anthropometric and medical information was obtained; and a fasting blood sample was used to measure glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin serum concentrations. Insulin resistance was assessed by the insulin resistance homeostasis model assessment. Body weight status (normal, overweight, and obese) was determined according to the International Obesity Task Force. Estimation of the MS was based on the International Diabetes Federation definition. The prevalence of the MS was 0.7% of children, all of whom were obese. Frequency of abdominal obesity, high fasting glucose, elevated triglycerides, low high-density-lipoprotein cholesterol, and elevated blood pressure was 4.8%, 4.7%, 0, 12.3%, and 33%, respectively. Body mass index (BMI) and z-BMI score increased significantly as the number of cardiometabolic risk factors increased. Regression analysis revealed that adiponectin (β = -0.501, P = .003) and leptin (β = 0.184, P < .0001) independently predicted the number of MS features. This finding was no longer significant after adjustment for BMI. In the present study, we provide the first estimate of the prevalence of the MS among healthy periadolescents in Greece using the International Diabetes Federation criteria. The MS prevalence was low, with elevated blood pressure being the most dominant feature. Finally, associations with adipokines are mediated by BMI.

The Gene-Diet Attica investigation on childhood obesity (GENDAI): overview of the study design

Abstract Background: There is limited evidence on the role of genetic and environmental factors in the etiology of childhood obesity, a major health problem worldwide. Methods: The Gene-Diet Attica Investigation on childhood obesity (GENDAI) evaluates the contributions to and pivotal interactions of genetic, dietary and physical activity variables on childrens weight. We describe the design, methodology, and present preliminary data. So far, 920 participants have been enrolled and the final projected sample is 1000 fifth- and sixth-grade students from selected elementary schools in Attica (10–14 years). In this school-based cross-sectional study, more than 400 variables describing anthropometric, dietary, clinical, genetic, sociodemographic and other lifestyle characteristics were collected from participating children and their families. Results: Increased body mass index was identified in 39.3% of subjects (30.5% overweight and 8.8% obese), with males presenting a more unfavorable metabolic profile, i.e., higher blood lipids, glucose, and insulin, compared to females. Normal-weight children had a significant advantage when compared to all children of increased weight in terms of lipid profile and insulin, as well as behaviors examined. Specifically, normal-weight children exhibited less skipping of meals and less sedentary activities. Conclusions: The overall high prevalence of overweight and obesity in the current population is significant and underscores the need for environmental and genetic information that will shed light on the phenomenon of childhood obesity. Clin Chem Lab Med 2007;45:309–15.

APOE, CETP and LPL genes show strong association with lipid levels in Greek children.

Background and aims Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL – S447X), cholesterol ester transfer protein (CETP – Taq1B) apolipoprotein (APO) E (ɛ2, ɛ3, ɛ4), APOA5 (−1131C > T and S19W), APOA4 (S347T) and APOC3 (−482C > T; 1100C > T and 3238G > C) on lipoprotein levels children from the Gene–Diet Attica Investigation on childhood obesity (GENDAI). Methods and results The ten variants selected were genotyped in 882 Greek children, mean age: 11.2 ± 0.7 years (418 females and 464 males). Genotypes were assessed using TaqMan technology. Significantly higher total cholesterol (TC) (p = 0.0001) and low-density lipoprotein cholesterol (LDL-C) (p < 0.0001) were observed in APOE ɛ4 carriers compared to ɛ3/ɛ3 homozygotes and ɛ2 carriers. The association of APOE genotype with TC and high-density lipoprotein cholesterol (HDL-C) ratio (p = 0.0008) was further modulated by body mass index. Carriers of the CETP TaqIB B2 allele had significantly higher HDL-C (p < 0.0001) and significantly lower TC: HDL-C ratio (p < 0.0001) compared to B1/B1 individuals. No significant associations were observed between APOA4, APOA5 and APOC3 variants and serum lipids. Conclusion This study demonstrates that these common variants are associated with lipid levels in this healthy paediatric cohort, suggesting that even in these young children there may be potential in predicting their lifelong exposure to an adverse lipid profile.

The effect of MTHFR(C677T) genotype on plasma homocysteine concentrations in healthy children is influenced by gender

Objective:To explore the influence of gender, together with folate status, on the relation between the common methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in healthy children.Design:Cross-sectional study by face-to-face interview.Setting and subjects:A total of 186 sixth-grade students participated from twelve randomly selected primary schools in Volos, Greece.Methods:Fasting tHcy, folate, and vitamin B12 were measured in plasma. The MTHFR genotypes were determined. Anthropometric and dietary intake data by 24-h recall were collected.Results:Geometric means for plasma tHcy, plasma folate and energy-adjusted dietary folate did not differ between females and males. The homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate concentrations (<19.9 nmol/l, P=0.012). As a significant gender interaction was observed (P=0.050), we stratified the lower plasma folate group by gender and found that the association between the genotype and tHcy was restricted to males (P=0.026). Similar results were obtained when folate status was based on estimated dietary folate. Specifically, only TT males that reported lower dietary folate consumption (<37 μg/MJ/day) had tHcy that was significantly higher than tHcy levels of C-allele carriers (P=0.001).Conclusions:Under conditions of lower folate status (as estimated by either plasma concentration or reported dietary consumption), gender modifies the association of the MTHFR(C677T) polymorphism with tHcy concentrations in healthy children.Sponsorship:Kellog Europe.

The Pro12Ala Polymorphism in PPARγ2 Gene Affects Lipid Parameters in Greek Primary School Children: A Case of Gene-to-Gender Interaction

Background:In the present study we sought to evaluate the impact of the PPAR-γ2 Pro12Ala polymorphism on blood lipid levels of primary school children. Methods:81 male and 92 female schoolchildren were genotyped. Biochemical, anthropometric, and lifestyle variables were assessed. Results:14.1% females and 14.8% males were heterozygotes, while the rest of the subjects were homozygotes for the Pro allele. A significant interaction between the PPARγ–2 gene and gender on blood lipid levels was detected. In particular, Pro/Pro females exhibited higher values of total cholesterol (194 ± 32 vs 180 ± 28 mg/dL, P = 0.06) and triglycerides (94 ± 31 vs 77 ± 11 mg/dL, P = 0.045) compared to Pro/Ala individuals. The gene-to-gender interaction term was highly significant (P < 0.001). On the other hand, Pro/Pro males showed higher values of HDL cholesterol (47 ± 8 vs 43 ± 9 mg/dL, P = 0.001), lower total cholesterol/HDL ratio (4.04 ± 0.59 vs 4.45 ± 0.61, P = 0.031), lower values of apoB (59.8 ± 11.3 vs 66.8 ± 6.6 mg/dL, P = 0.007) and lower values of apoB/apoA1 ratio (0.41 ± 0.09 vs 0.48 ± 0.08, P = 0.019) compared with Pro/Ala. Even after adjusting for body mass index (BMI), total energy intake, total fat intake and saturated fat intake, differences in total cholesterol/high-density lipoprotein (HDL) cholesterol and the apoB/apoA1 ratios remained significant. Regarding females, no differences were observed among genotypes concerning total cholesterol/HDL levels (P for gene-to-gender interaction = 0.001) and the apoB/apoA1 levels (P for gene-to-gender interaction = 0.029). Conclusion:We show for the first time a gene-to-gender interaction on total cholesterol/HDL and apoB/apoA1 ratios, in male schoolchildren genotyped for PPAR-γ2 Pro12Ala.

An age-dependent diet-modified effect of the PPARγ Pro12Ala polymorphism in children

Variation in the peroxisome proliferator-activated receptor γ gene alters the risk for adiposity in adults, with evidence of interaction with diet. We investigated the age-related association between the Pro12Ala variant (rs1801282) and diet in obesity-related traits in children. The Pro12Ala variant was assayed in 2102 young children aged 1 to 6 years and in 794 periadolescent children aged 10 to 12 years of Greek origin. In both cohorts, no differences were found in obesity traits between the Ala allele carriers and Pro/Pro homozygotes. Sex-stratified analysis showed that, in periadolescent boys, Ala carriers exhibited lower measures of skinfolds (triceps: 16.9 ± 6.9 vs 19.4 ± 7.9 mm, P = .01; subscapular: 9.6 ± 4.5 vs 11.2 ± 5.4 mm, P = .02). On the other hand, young girls who were Ala carriers presented higher measures of triceps skinfold thickness (10.5 ± 3.0 vs 9.9 ± 2.8 mm, P = .04). Nominal gene-diet interactions were revealed in periadolescents for saturated fatty acid (SFA) intake and skinfolds (P for interaction = .05). In Pro/Pro homozygous young girls, SFA and total fat (TF) intake was positively associated with higher body mass index (BMI) (P = .01), waist circumference (P = .02), and skinfold thickness (triceps-SFA: P = 10⁻⁵, triceps-TF: P = 10⁻⁹, subscapular-SFA: P = 10⁻⁶, subscapular-TF: P = 10⁻⁴). For Pro/Pro homozygotes, unsaturated fat intake was inversely associated with BMI (P = .04) in young girls, and with BMI (P = .03), waist circumference (P = .03), and triceps (P = .02) in periadolescent boys. Our results suggest that adiposity in children is influenced by the Pro12Ala polymorphism in a sex-specific and age-dependent manner. We also demonstrate evidence of an age-dependent gene-diet (SFA, TF) interaction, suggesting that the type of fat intake modifies the effect of the Pro12 allele on obesity-related measures.