METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.
RESULTS: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10-8 to 3.27×10-18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10-7), higher triglyceride levels (P = 5.37×10-9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10-10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P
Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.
Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.
Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.
METHODS: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline.
RESULTS: High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively.
CONCLUSIONS: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
METHODS: This cross-sectional study was conducted among 555 (164 men, 391 women) Orang Asli adults aged 18-65 years of Jah Hut sub-tribe in Krau Wildlife Reserve (KWR), Peninsular Malaysia. Demographic and socio-economic information were obtained using interviewer-administered questionnaire. Participants were also assessed for serum 25-hydroxyvitamin D (25(OH)D) concentration, adiposity indices (BMI, WC, WHtR, WHR, %BF) and lipid parameters (TC, LDL-C, HDL-C, TG). Data were analyzed using binary logistic regression via SPSS.
RESULTS: The prevalence of suboptimal 25(OH)D concentration was 26.3%, comprising 24.9% insufficiency (50 to <75 nmol/L) and 1.4% deficiency (<50 nmol/L). While men (14-30.5%) were associated with a more proatherogenic lipid profile than women (6.1-14.3%), more women were with central obesity (M: 19.5-46.3%; F: 34.5-49.1%) and suboptimal (<75 nmol/L) vitamin D status (M: 11.6%; F: 32.4%). While suboptimal 25(OH)D concentration was significantly associated with higher odds of at-risk LDL-C (p < 0.01) and obesity (WC, WHtR) (p < 0.05) in men, no significant association was observed for women. Nonetheless, it should be noted that there were only 19 men with suboptimal (<75 nmol/L) vitamin D status.
CONCLUSIONS: While suboptimal vitamin D status was relatively low in Orang Asli adults, the prevalence of obesity and undesirable serum lipids were relatively high. The sex-specific associations between vitamin D status with adiposity indices and serum lipids warrant further investigation.
Methods: We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.
Results: PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.
Conclusion: Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.
METHODS AND RESULTS: A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist-hip ratio, and waist-height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35-74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40-74 years were 2.32 [95% confidence interval (CI) 1.84-2.94] for waist circumference, 2.22 (1.71-2.88) for the waist-hip ratio, 2.63 (2.06-3.36) for the waist-height ratio, and 1.58 (1.29-1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27-1.41), 1.31 (1.23-1.39), 1.38 (1.31-1.45), and 1.18 (1.13-1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75-0.86).
CONCLUSIONS: In this study of Mexican adults, abdominal adiposity (and in particular the waist-height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.
METHOD: A quasi-randomized controlled trial was conducted recruiting students from two different higher learning institutions in Kuantan, Pahang, Malaysia. Students are selected after fulfilling the criteria such as body mass index (BMI) of ≥23kg/m2, no chronic diseases that may influence by exercise, no significant changes in body weight within two months and not taking any medications or supplements. One institution was purposely chosen as a simulation-based group and another one control group. In the simulation-based group, participants were given a booklet and CD to do aerobic and resistance exercise for a minimum of 25min per day, three times a week for 10 weeks. No exercise was given to the control group. Participants were measured with the International Physical Activity Questionnaire (IPAQ), BMI, waist circumference (WC), body fat percentage before and after 10 weeks of simulation-based exercise.
RESULTS: A total of 52 (control: 25, simulation-based: 27) participants involved in the study. There was no baseline characteristics difference between the two groups (p>0.005). All 27 participants in the simulation-based group reported performing the exercise based on the recommendation. The retention rate at three months was 100%. No adverse events were reported throughout the study. Better outcomes (p<0.001) were reported among participants in the simulation-based group for BMI, WC and body fat percentage.
CONCLUSIONS: The findings of this study indicate that the simulation-based exercise programme may be feasible for an overweight adult in higher learning institutes. As a feasibility study this is not powered to detect significant differences on the outcomes. However, participants reported positive views towards the recommended exercise with significant improvements in body mass index, body fat percentage and reduced the waist circumference.
METHODS: A total of 110 putatively healthy and non-obese subjects were divided into three groups according to their level of VF and BP. Common carotid artery BFV was measured using a developed portable Doppler ultrasound measurement system.
RESULTS: The most pronounced peak systolic velocity (S1) was lower (p < 0.05) in the hypertensive group and the peak diastolic velocity (D) was significantly lower in the pre-hypertensive group than in the normotensive group. There were differences in velocity reflection and resistive indices between the hypertensive and other two BP groups. The higher VF group had significantly lower S1 and D velocities and resistive and vascular elasticity indices. By contrast, the velocity reflection index was larger in the higher VF group.
CONCLUSIONS: We confirmed that there were significant differences in the BFV among non-obese subjects who differed in level of VF and BP. This study confirms that a putatively increasing VF and BP level is associated with the development of hypertension.