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Eating behaviour traits of rigid control and disinhibition have been associated with body weight in both adults and adolescents. Moreover, adults reporting a dieting history have increased levels of unhealthy eating behaviours. Against this background, the present study aimed to examine the relationship between dieting history and eating behaviour traits in adolescents. For the purpose of this research, a total of sixty adolescents (aged 15 (sem 2·4) years) from the Québec Family Study completed the Three-Factor Eating Questionnaire (TFEQ) and a questionnaire regarding eating habits. Self-reported current and past dieting were analysed against eating behaviour traits measured by the TFEQ, including all subscales. As the results revealed, few adolescents reported currently dieting (n 3). Adolescents who reported a dieting history (23·3 %) were older (16·9 v. 14·4 years, P < 0·001), were more likely to be female (78·6 v. 41·3 %, P < 0·05) but did not have a significantly higher BMI z-score (1·5 v. 0·9, P = 0·10), although they were more likely to be either overweight or obese (P < 0·01). After correcting for sex, BMI and age, adolescents who reported a dieting history had higher levels of rigid control and disinhibition (P < 0·05-0·0001) than those reporting no dieting history. A greater proportion of adolescents characterised by high rigid control and high disinhibition were past dieters, compared to those characterised by low levels of both behaviour traits (53 v. 4 %). The study arrived at the following conclusions: as observed in adults, adolescents with a history of dieting present unfavourable eating behaviour traits. These behavioural traits may represent an additional challenge to the long-term regulation of body weight.

Introduction: Elevated plasma triglycerides (TG) are associated with risk of cardiovascular disease and are modifiable through lifestyle interventions such as regular exercise. However, TG responses to regular exercise are characterized by significant inter-individual differences. Hypothesis: We hypothesized that baseline levels of circulating proteins and metabolites are associated with TG response to exercise and can predict exercise-induced changes in plasma TG traits. Methods: We measured circulating proteins (n=4979 proteins) and metabolites (n=300) in 650 Black and White adults of the HERITAGE Family Study who completed 20 weeks of exercise training and had complete data on TG traits. We investigated two TG-related traits that significantly improved with training: fasting TG and large TG-rich lipoprotein particle concentration (LTRLP). The association between baseline analyte values and exercise-induced changes in TG traits were examined using linear mixed models adjusted for age, sex, race, BMI, baseline trait value, and the random effect of family membership. Significance was determined as FDR&lt;0.05. Molecular signatures of TG trait responses were generated via elastic net regression tuned using leave-one-out cross validation. Results: Regular exercise significantly reduced plasma TG (-1.03±1.3 mmol/L, p=0.01) and LTRLP (-0.24±2.2 nmol/L, p= 0.007), with their training-induced changes moderately correlated (r=0.4, p&lt;0.0001). We identified largely distinct panels of baseline analytes associated with changes in TG and LTRLP ( Table 1 ). Similarly, elastic net regression yielded distinct models of 99 analytes for TG and 315 analytes for LTRLP responses to exercise with accuracy of RMSE=1.28 mmol/L for TG and 2.16 nmol/L for the LTRLP model. Conclusions: We identified panels of proteins and metabolites associated with exercise-induced changes in TG traits and demonstrate, within our data, circulating analytes hold promise for predicting the exercise responsiveness of plasma TG-related traits.

Apolipoprotein C-II (ApoC-II) is thought to activate lipoprotein lipase (LPL) and is therefore a possible target for treating hypertriglyceridemia. Its relationship with cardiovascular risk has not been investigated in large-scale epidemiologic studies, particularly allowing for apolipoprotein C-III (ApoC-III), an LPL antagonist. Furthermore, the exact mechanism of ApoC-II-mediated LPL activation is unclear.ApoC-II was measured in 3141 LURIC participants of which 590 died from cardiovascular diseases during a median (inter-quartile range) follow-up of 9.9 (8.7-10.7) years. Apolipoprotein C-II-mediated activation of the glycosylphosphatidylinositol high-density lipoprotein binding protein 1 (GPIHBP1)-LPL complex was studied using enzymatic activity assays with fluorometric lipase and very low-density lipoprotein (VLDL) substrates. The mean ApoC-II concentration was 4.5 (2.4) mg/dL. The relationship of ApoC-II quintiles with cardiovascular mortality exhibited a trend toward an inverse J-shape, with the highest risk in the first (lowest) quintile and lowest risk in the middle quintile. Compared with the first quintile, all other quintiles were associated with decreased cardiovascular mortality after multivariate adjustments including ApoC-III as a covariate (all P < 0.05). In experiments using fluorometric substrate-based lipase assays, there was a bell-shaped relationship for the effect of ApoC-II on GPIHBP1-LPL activity when exogenous ApoC-II was added. In ApoC-II-containing VLDL substrate-based lipase assays, GPIHBP1-LPL enzymatic activity was almost completely blocked by a neutralizing anti-ApoC-II antibody.The present epidemiologic data suggest that increasing low circulating ApoC-II levels may reduce cardiovascular risk. This conclusion is supported by the observation that optimal ApoC-II concentrations are required for maximal GPIHBP1-LPL enzymatic activity.

1885 We determined the reproducibility of plasma substrates in the HERITAGE Family Study protocol assayed in 60 subjects (25F, 35M, aged 19 - 55 yrs) at rest, 50W, 60% ˙VO2max, 80% ˙VO2max, and at˙VO2max. Blood samples were collected in a non-fasting state on 3 separate days within a 3-wk period to assess within subject day-to-day variation (DD). Technical error (TE) was determined by generating split samples which were assayed in a blind fashion and compared to original samples. Means ([horizontal bar over]x), DD and intraclass correlation coefficients (ICC) for the repeated tests are shown below for glucose, FFA and total proteins: TableTableTE ranged from 0.07 to 0.11 mM, 10 to 13 μM and 0.9 to 1.2 g/L for glucose, FFA and total proteins, respectively. We conclude that the TE is low, DD is high and the ICC is moderate for these substrates during the exercise protocol.

542 This study examined the gender differences in response of the ventilatory threshold to 20 weeks (3x/wk) of supervised cycle ergometry training in a biracial population of men (n=232) and women (n=208), ages 17-65 years. Participants in the HERIT AGE Family Study completed a heart rate-based training program progressing from a heart rate associated with 55% VO2max for 30 min to training at 75% VO2max for 50 min. Ventilatory threshold (VT) was estimated using V-Slope and ventilatory equivalents methods. Percent change for pre-post training values for selected variables are listed in the Table below.TableAn ANOVA between men and women across pre- post-training (Sex X Time) revealed no interaction for change in VO2max (ml·kg−1·min−1). However, there were highly significant Sex X Time interactions (p<0.0001) for improvements in VO2 at VT (VO2VT), increases in relative VT (RVT=VO2VT/VO2max * 100), increases in watts at VT (WVT), and increases in maximal watts (WMx) achieved during the post-training cycle egrometry test. These data show similar improvements in VO2max for men and woman, but strong gender differences in submaximal training-induced changes in VO2 and work at VT. This suggests that submaximal measurements of aerobic fitness reveal different aspects of improvements in fitness than the "gold standard" of VO2max. Sponsored by NHLBI HL47317 and NIH MO1-RR000400.

The Eating Pattern Assessment Tool (EPAT) is a short, self-administered questionnaire designed to give health care providers a simple method for assessing dietary lipids intake for counseling purposes. The validity and reliability of this tool were previously demonstrated in an upper midwestern clinical population. The EPAT was used in the HERITAGE Family Study to track the consistency of dietary intake of fat and cholesterol by participants throughout a 20-week exercise training period. Participants were 390 sedentary individuals from 70 Caucasian and African-American families, aged 16 to 66 yrs, from 4 regions of North America. At baseline, participants completed both sections of the EPAT (PRE), filled out the Willett semi-quantitative food frequency questionnaire (FFQ), and had blood taken for a pre-training lipid profile. Subjects repeat-ed the EPAT at week 10 (MID) and at week 20 (POST). Section I of the baseline EPAT showed reasonably good, highly significant correlations (r=0.40 to 0.55) with fat and cholesterol items from the FFQ(P<.0001). However, no such correlations were found for Section II. Both sections of the PRE, and fat and cholesterol related items from the FFQ, were poorly correlated with plasma total cholesterol and its lipoprotein fractions. Intraclass correlations coefficients for PRE, MID, and POST scores reached 0.78 for Section I and 0.65 for Section II, coefficients comparable to those previously reported from a less diverse population not participating in an exercise program. We conclude that our study participants were consistent through-out the exercise program in their dietary intake of fat and cholesterol. Our results also confirm the repeatability of the EPAT and the validity of Section I in tracking dietary lipid intake in a diverse population during an extended exercise training study.

Obesity, especially central obesity, and cigarette smoking (SMK) are both important risk factors for cardiovascular disease (CVD). Yet, smokers often exhibit lower body mass index (BMI) and higher waist circumference (WC) compared to non-smokers; also, smoking cessation leads to weight gain. Genome-wide association (GWA) studies have identified genetic loci that are associated with risk of overall and central obesity; yet little is known about whether and how SMK influences the genetic susceptibility to obesity. This study aims to discover genetic loci that are associated with obesity, measured as BMI and WC adjusted for BMI (WC a ), and where the effects are hidden by SMK. We used results from 42 studies including up to 126,767 subjects with GWA data available through the GIANT Consortium. Each study employed three association models while considering smoking status (current vs. not current smokers): 1) SNP effects adjusted for SMK (SNPadjSmk), 2) SNP by SMK interaction effects (SNPxSMK), and 3) joint effect of SNP and the SNP x SMK interaction effect (SNPxSMK J ). Study specific results were combined by inverse-variance weighted fixed-effects meta-analyses of the study specific results in men and women separately and then combined sexes. A total of 53 SNPs for WC a reached genome-wide significance (GWS) (p&lt;1E-8) by adjusting for and allowing for interaction with SMK (SNPadjSMK and SNPxSMK J ), 27 of these loci are novel for WC a . Additionally, SNPadjSMK and SNPxSMK J models identified a total of 49 SNPs associated with BMI that reached GWS, including 15 novel loci. While no loci reached GWS for SNPxSMK on BMI, one novel SNPxSMK association with WC a near PRNP reached GWS in women. PRNP is highly expressed throughout the CNS and especially the hippocampus, as are many obesity-related genes. PRNP also plays a role in the body’s response to oxidative stress, making it a likely candidate gene for interaction with smoking as well. Of the GWS SNPs, 47 WC a and 41 BMI loci are nearby (&lt;500 kb) previously established loci for traits of interest (e.g. SMK, obesity, CVD, VAT, lipids, T2D, T1D and other anthropometrics). We identify one locus with strong evidence of interaction with SMK on obesity, and notably, we find several new loci associated with obesity by accounting for the influence of SMK. Our results highlight the importance of appropriately modeling genetic associations by considering known biological relationships between phenotypes and the environment.

High-throughput proteomics allows researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (N = 2,631) and IVGTT-derived measures in participants from the HERITAGE Family Study (N = 752). We characterize 51 proteins that were associated with longitudinal diabetes risk, using their respective 39, 9, and 8 concurrent associations with insulin sensitivity index (SI), acute insulin response to glucose (AIRG), and glucose effectiveness (SG). Twelve of the 51 diabetes associations appear to be novel, including β-glucuronidase, which was associated with increased diabetes risk and lower SG, suggesting an alternative pathway to insulin for glucose disposal; and plexin-B2, which also was associated with increased diabetes risk, but with lower AIRG, and not with SI, indicating a mechanism related instead to pancreatic dysfunction. Other novel protein associations included alcohol dehydrogenase-1C, fructose-bisphosphate aldolase-B, sorbitol dehydrogenase with elevated type 2 diabetes risk, and a leucine-rich repeat containing protein-15 and myocilin with decreased risk. Article Highlights Plasma proteins are associated with the risk of incident diabetes in older adults independent of various demographic, lifestyle, and biochemical risk factors. These same proteins are associated with subtle differences in measures of glucose homeostasis earlier in life. Proteins that are associated with lower insulin sensitivity in individuals without diabetes tend to be associated with appropriate compensatory mechanisms, such as a stronger acute insulin response or higher glucose effectiveness. Proteins that are associated with future diabetes risk, but not with insulin insensitivity, tend to be associated with lower glucose effectiveness and/or impaired acute insulin response.

Background: A high waist-to-hip ratio is associated with unfavorable cardiovascular disease risk factors. This could be due to either a relatively large waist or a small hip girth. Objective: We sought to define the separate contributions of waist girth, hip girth, and body mass index (BMI) to measures of body composition, fat distribution, and cardiovascular disease risk factors. Design: Three-hundred thirteen men and 382 women living in the greater Quebec City area were involved in this cross-sectional study. Percentage body fat, anthropometric measurements, and abdominal fat distribution were obtained and BMI (in kg/m2) and waist-to-hip ratio were calculated. Serum blood lipids were determined from blood samples collected after subjects had fasted overnight Results: A large waist circumference in men and women (adjusted for age, BMI, and hip circumference) was associated significantly with low HDL-cholesterol concentrations ( P < 0.05) and high fasting triacylglycerol, insulin, and glucose concentrations ( P < 0.01). In women alone, a large waist circumference was also associated with high LDL-cholesterol concentrations and blood pressure. A narrow hip circumference (adjusted for age, BMI, and waist circumference) was associated with low HDL-cholesterol and high glucose concentrations in men ( P < 0.05) and high triacylglycerol and insulin concentrations in men and women ( P < 0.05). Waist and hip girths showed different relations to body fat, fat-free mass, and visceral fat accumulation. Conclusions: Waist and hip circumferences measure different aspects of body composition and fat distribution and have independent and often opposite effects on cardiovascular disease risk factors. A narrow waist and large hips may both protect against cardiovascular disease. These specific effects of each girth measure are poorly captured in the waist-to-hip ratio.

Objective: To investigate familial basis for the relationship between cortisol adiposity at baseline and their training responses. Research Methods and Procedures: Bivariate correlation and segregation analyses were employed between cortisol and several adiposity measures [body mass index, fat mass (FM), fat‐free mass, percentage of body fat (% BF), abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF)] from 99 white families and 105 black families. Results: In both races, significant inverse phenotypic correlations were generally observed between cortisol and adiposity measures at baseline but not for training responses. Significant cross‐trait familial correlations were found for cortisol with abdominal fat (ASF, AVF, ATF) and overall body adiposity (FM, % BF) measures at baseline, which accounted for 14% to 20% of the phenotypic variance in whites. The cross‐trait correlations were not significant for baseline phenotypes in blacks, perhaps because of the small sample size. A bivariate segregation analysis showed evidence of polygenic pleiotropy for cortisol with both abdominal fat and overall adiposity measures that accounted for 14% to 17% of the phenotypic covariance, but major gene pleiotropy was not suggested in whites. However, when ASF, AVF, and ATF were additionally adjusted for FM, no familial cross‐trait correlations or polygenic pleiotropy between cortisol and the abdominal fat measures remained. Discussion: Evidence was found for polygenic pleiotropy but not for pleiotropic major gene effects between cortisol and overall adiposity in whites. However, the covariation of cortisol with abdominal fat phenotypes is dependent on concomitant polygenic factors for total‐body fat.

It has been suggested that genetic variation in the angiotensin-converting enzyme ( ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian ( n = 476) and black ( n = 248) subjects. Phenotypes measured were oxygen uptake (V˙o 2 ), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximalV˙o 2 (V˙o 2 max )] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60%V˙o 2 max ). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant ( P values from 0.042 to 0.0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14–38% greater increase with training in V˙o 2 max ,V˙o 2 at 80% ofV˙o 2 max , and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

No abstract is provided for this article.

To identify loci-harboring genes affecting steroid hormone and SHBG plasma levels, a genomic-wide scan was performed in the HERITAGE Family Study at baseline. The following steroid hormones were assayed: androstane-3 alpha, 17 beta-diol glucuronide, androsterone glucuronide, cortisol, dihydrotestosterone, estradiol, 17-hydroxyprogesterone (OH-PROG), progesterone (PROG), pregnenolone ester, and testosterone. A total of 509 markers on the 22 autosomes were genotyped, and a maximum of 357 pairs of siblings from white families and 103 from black families were available for the study. Significant linkages with LOD scores over 3.6 (P < 2.2 x 10(-5)) for SHBG were observed in blacks on 1q44 (D1S321), 5p13.3 (D5S1986), 10q24.1 (D10S1239), and 12q12 (D12S1653) in both singlepoint and multipoint analyses. Promising evidence of linkage (1.75 < LOD < 3.6; 2.2 x 10(-5) < P < 0.0023) for SHBG was observed on 1q44 in singlepoint analysis in whites. In addition, several other loci in blacks exhibited promising evidence of linkage, suggesting that many genes can potentially regulate SHBG levels. In the case of C21 steroids, promising linkages were found on 1q43 (D1S517) for PROG, 2p25.1 (D2S1400) for pregnenolone ester, and 18q21.32 (D18S38) for OH-PROG in whites and on 3q25.33 (D3S1763) for OH-PROG in blacks, both singlepoint and multipoint analyses (P < 0.0023). The strongest signals for C19 steroids were found on 22q12.3 for testosterone in whites (P = 0.0024 in multipoint) and on 8q22.1 for dihydrotestosterone in blacks. In blacks, the strongest evidence of linkage for estradiol (C18 steroid) was provided by marker D1S1588 on 1p21.3 and in whites by markers D2S2374 and D2S2347 on 2p21, and D6S465 on 6p12.3. Several genes encoding enzymes of the steroid biosynthesis pathways but also other potential candidate genes were located in the vicinity of the genomic regions showing evidence of linkage in this genomic scan.