Effects of FTO genotype on weight loss and metabolic risk factors in response to calorie restriction among Japanese women

Effects of gene variants in the fat-mass and obesity-associated (FTO) gene (primarily rs9939609) on weight loss induced by lifestyle intervention are controversial. The aim of this study was to investigate whether FTO gene variations are associated with weight-reduction and changes in metabolic risk factors in response to a 14-week calorie restriction. In total, 204 Japanese women (aged 24-66 years; BMI ≥ 25 kg/m(2)) enrolled as subjects and attended dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Fat mass, both at baseline (P = 0.100) and after the intervention (P = 0.020), was higher in subjects with the AA genotype (n = 15; 7.3%) than in those with TT (n = 114; 55.9%) and TA (n = 75; 36.8%) genotypes. The change in fat-mass tended to be smaller in subjects with the AA genotype than in those with other genotypes (P = 0.065). However, the subjects with the risk allele could still decrease their body weight and improve metabolic risk factors significantly. Our data suggest that the impact of FTO rs9939609 in Japanese women may not be great enough to change body weight or metabolic risk factors in response to calorie restriction. Environmental and behavioral factors may overcome the effects of genes on weight reduction.     

The Common Variant in the FTO Gene Did Not Modify the Effect of Lifestyle Changes on Body Weight: The Finnish Diabetes Prevention Study

The common single‐nucleotide polymorphism in the FTO (fat mass and obesity associated) gene is consistently associated with an increased risk of obesity. However, the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited. We examined whether the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and long‐term weight changes in the Finnish Diabetes Prevention Study (DPS). Altogether, 522 (aged 40–65 years; BMI ≥25 kg/m²) subjects with impaired glucose tolerance (IGT) were randomized to control and lifestyle intervention groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with the AA genotype had higher BMI than subjects with other genotypes (P = 0.006). The association was observed in women (P = 0.016) but not in men. During the 4‐year follow‐up, the subjects with the AA genotype had consistently the highest BMI (P = 0.009) in the entire study population. The magnitude of weight reduction was greater in the intervention group, but the risk allele did not modify weight change in either of the groups. Our results confirm the association between the common FTO variant and BMI in a cross‐sectional setting and during the long‐term lifestyle intervention. We did not observe association between FTO variant and the magnitude of weight reduction achieved by long‐term lifestyle intervention. Based on the results from the DPS, it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss.     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

Meta‐analysis Added Power to Identify Variants in FTO Associated With Type 2 Diabetes and Obesity in the Asian Population

Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10^?3; rs9939609, P = 9.8 × 10^?4; for obesity, rs8050136, P = 2.2 × 10^?7; rs9939609, P = 9.0 × 10^?9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.     

FTO at rs9939609, Food Responsiveness,Emotional Control and Symptoms of ADHD in Preschool Children

The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)²) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO.     

Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development

An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p?=?10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p?=?10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p?=?0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p?=?0.01), and earlier AR (-4.72% (-5.81, -3.63), p?=?10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.     

Prospective associations between measures of adiposity and periodontal disease

Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.     

Examining for an association between candidate gene polymorphisms in the metabolic syndrome components on excess weight and adiposity measures in youth: a cross-sectional study

Background

A polymorphism in a gene may exert its effects on multiple phenotypes. The aim of this study is to explore the association of 10 metabolic syndrome candidate genes with excess weight and adiposity and evaluate the effect of perinatal and socioeconomic factors on these associations.

Methods

The anthropometry, socioeconomic and perinatal conditions and 10 polymorphisms were evaluated in 1081 young people between 10 and 18 years old. Genotypic associations were calculated using logistic and linear models adjusted by age, gender, and pubertal maturation, and a genetic risk score (GRS) was calculated by summing the number of effect alleles.

Results

We found that AGT-rs699 and the IRS2-rs1805097 variants were significantly associated with excess weight, OR = 1.25 (CI 95% 1.01–1.54; p = 0.034); OR = 0.77 (CI 95% 0.62–0.96; p = 0.022), respectively. AGT-rs699 and FTO-rs17817449 variants were significantly and directly associated with body mass index (BMI) (p = 0.036 and p = 0.031), while IRS2-rs1805097 and UCP3-rs1800849 were significantly and negatively associated with BMI and waist circumference, correspondingly. Each additional effect allele in GRS was associated with an increase of 0.020 log(BMI) (p = 0.004). No effects from the socioeconomic and perinatal factors evaluated on the association of the candidate genes with the phenotypes were detected.

Conclusions

Our observation suggests that AGT-rs699 and FTO-rs17817449 variants may contribute to the risk development of excess weight and an increase in the BMI, while IRS2-rs1805097 showed a protector effect; in addition, UCP3- rs1800849 showed a decreasing waist circumference. Socioeconomic and perinatal factors had no effect on the associations of the candidate gene.

     

FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women

The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control study of 1,517 diabetes cases and 2,123 controls from the Women's Health Initiative-Observational Study (WHI-OS). The allelic frequencies of either rs9939609 or rs8050136 differed widely across four ethnic groups. The frequency of the rare allele A of rs9939609 among controls was much lower in Asians/Pacific Islanders (17%) than in blacks (45%), whites (40%), and Hispanics (31%). We found significant associations of rs9939609 with BMI and waist circumference in white and Hispanic women, but not among black and Asian/Pacific Islander women. On average, each copy of the risk-allele A at rs9939609 was significantly associated with 0.45 kg/m(2) increase in BMI (95% confidence interval (CI): 0.16-0.74; P = 0.004) and 0.97 cm increase in waist circumference (95% CI: 0.21-0.65; P = 0.0002). Similar results were observed for rs8050136. However, we found no significant genetic associations with diabetes risk, either within the full study sample or in any ethnic group. In conclusion, common genetic variants in the intron 1 of FTO gene may confer a modest susceptibility to obesity in an ethnicity-specific manner, but may be unlikely to contribute to a clinically significant diabetes risk.     

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

Background

Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.

Aim

We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.

Methods and Findings

Participants, aged 20–60 years at baseline, came from five European countries. Cases (‘weight gainers’) were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a ‘weight gainer’ (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2×10⁻⁷).

Conclusions

We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.     

Associations between an obesity related genetic variant (FTO rs9939609) and prostate cancer risk

Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA <0.5 ng/ml). The rs9939609 A allele, which was associated with higher BMI in the sample, was inversely associated with overall (odds ratio (OR) versus all controls = 0.93; 95% confidence interval (CI): 0.85-1.02 p = 0.12 per allele) and low-grade (OR = 0.90; 0.81-0.99 p = 0.03 per allele) prostate cancer risk, but positively associated with high-grade cancer among cases (OR high- versus low-grade cancer = 1.16; 0.99-1.37 p = 0.07 per allele). Although evidence for these effects was weak, they are consistent with observational data based on BMI phenotypes and suggest that the observed association between obesity and prostate cancer is not due to confounding. Further research should confirm these findings, extend them to other BMI-related genetic variants and determine whether they are due to detection bias or obesity-related hormonal changes. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN20141297.     

Birth weight and subsequent adiposity gain in Swedish children and adolescents: a 6-year follow-up study

We examined whether birth weight (BW) predicts changes in body composition over a 6-year period in Swedish children and adolescents. For this purpose, a total of 247 children (55.5% girls) and 162 adolescents (60.5% girls) were included in the study and were followed up 6 years later. BW was obtained from parental records. We measured weight, height, waist circumference, and the bicep, tricep, subscapular, suprailiac, and medial calf skinfolds, and we calculated BMI, fat-free mass (FFM), and the sum of five skinfolds. Physical activity was assessed by accelerometry. Changes in pubertal status and baseline anthropometric estimates were used as confounders in all analysis. In the children cohort, we observed that BW was inversely associated with changes in BMI (β = -0.736, P = 0.002) and the sum of five skinfolds (β = -6.381, P = 0.009) regardless of confounders and physical activity, only in girls. We did not find any significant association between BW and adiposity gain estimates in the adolescent cohort. These findings give further support to the concept that low BW may have a programming effect of subsequent adiposity gain from childhood to adolescence. We also confirm the sex-related differences in the programming effect of body composition.     

Weight change and cognitive function: findings from the Women's Health Initiative Study of Cognitive Aging

Although studies exploring relationships between obesity and cognitive impairment in the elderly are conflicting, literature suggests that overweight and obesity may be protective against cognitive impairment and dementia in older women. We examine the associations between changes in weight and waist circumference (WC) with global and domain-specific cognitive function in a large, well-defined cohort of 2,283 older, postmenopausal women (aged 65-79) prospectively followed through the Women's Health Initiative (WHI) Study of Cognitive Aging (WHISCA). We assessed the associations between changes in weight and WC collected up to 5 years before WHISCA enrollment and mean levels of global and domain-specific cognitive performance across an average of 5.4 years of subsequent follow-up. There was a lack of associations between weight and cognition in women who remained stable or gained weight. The only significant relationships observed were in association with weight loss (P ≤ 0.05), most likely signaling incipient disease. Moreover, cognition was not related to changes in WC. Relationships were largely independent of initial BMI, self-reported caloric intake or dieting. The lack of associations between weight gain and cognition in women is consistent with the existing literature.     

Association of the FTO gene with BMI

Variants in the FTO gene have been strongly associated with obesity in a very large sample (38,759) of diabetic and control subjects. To replicate these findings, the previously reported SNP in the FTO gene (rs9939609, T/A) was genotyped in 5,607 subjects from five different Utah studies. The studies included a random sample of the Utah population, families selected for aggregation of extreme thinness, families selected for severe obesity, a series of unrelated severe obesity subjects, and families participating in a 25-year longitudinal study of cardiovascular disease and aging. Results show a strong significant increase in the rs9939609 A allele frequency with increasing BMI (P < 0.0001). In the longitudinal study, FTO genotypes were significantly associated with BMI at a baseline exam, a 2(1/2)-year follow-up exam and a 25-year follow-up exam using an additive genetic model. The mean genotype difference in BMI ranged from 1.3 to 2.1 kg/m(2) across exams. The genotype difference in BMI means was established in youth, and at-risk subjects under age 20 at baseline had a significantly larger 25-year BMI increase (10.0 for A/A; 9.7 for A/T, and 8.5 kg/m(2) for T/T, P = 0.05). We conclude that the BMI increases associated with FTO genotypes begin in youth and are maintained throughout adulthood.     

Obesity and vital exhaustion: analysis of the Atherosclerosis Risk in the Communities study

This study aimed to determine whether vital exhaustion (VE) was associated with BMI cross-sectionally and after 3 and 6 years of follow-up. Extant data from the Atherosclerosis Risk in Communities (ARIC) study were used to examine the relationship between VE and BMI among 13,727 white and African-American adults cross-sectionally (baseline) and longitudinally (3 and 6 years later). We used adjusted and nonadjusted general linear regression models. Associations with excess weight gain (>or=5.0%) were also examined using logistic regression. Results showed that BMI was significantly higher among both white and African-American men and women in the highest VE quartile compared to those with no VE. Similarly, high VE at baseline was associated with higher BMI 3 and 6 years later, although VE was not able to predict future BMI after adjusting for baseline BMI. Baseline VE predicted future excess weight gain in white men and women, but not in African Americans. These results suggest that reducing VE levels may play an important role in reducing the prevalence of obesity. High VE was associated with higher current BMI (all races) and excess weight gain (whites only). Although high VE predicted future weight gain without baseline BMI adjustment, the magnitude of change in BMI over time was similar among those with low and high VE; suggesting that any relationship between VE and BMI was already established at baseline. Assessment of VE and BMI over time would help to elucidate uncertainties between the temporal nature of the relationship between them.     

A prospective study of breakfast consumption and weight gain among U.S. men

Objective: The aim was to investigate the association between breakfast consumption and long‐term weight gain in an adult male population. Research Methods and Procedures: We evaluated prospective data on 20,064 U.S men, 46 to 81 years of age, who participated in the Health Professionals Follow‐up Study. Data on body weight, dietary factors, and lifestyle variables were obtained by validated questionnaires. We examined weight gain during 10 years of follow‐up. Results: Overall, 5857 men had a weight gain of 5 kg or greater during 10 years of follow‐up. Breakfast consumption was inversely associated with the risk of 5‐kg weight gain after adjustment for age [hazard ratio (HR) = 0.77 (95% confidence interval [CI], 0.72 to 0.82)], and this association was independent of lifestyle and BMI at baseline [HR = 0.87 (95% CI, 0.82 to 0.93)]. Fiber and nutrient intakes partially explained the association between breakfast consumption and weight gain. The inverse association between breakfast consumption and weight gain was more pronounced in men with a baseline BMI of 25 kg/m² or lower [multivariate HR = 0.78 (95% CI, 0.70 to 0.87)] than in men who were overweight at baseline [HR = 0.92 (95% CI, 0.85 to 1.00)]. Furthermore, we observed that an increasing number of eating occasions in addition to three standard meals was associated with a higher risk of 5‐kg weight gain [HR = 1.15 (95% CI, 1.06 to 1.25, for ≥2 vs. 0 additional eating occasions)]. Discussion: These findings suggest that the consumption of breakfast may modestly contribute to the prevention of weight gain as compared with skipping breakfast in middle‐aged and older men.     

Weight loss and sleep-disordered breathing in childhood obesity: effects on inflammation and uric acid

Sleep-disordered breathing (SDB) is prevalent in childhood obesity. It may be an independent risk factor for the metabolic syndrome. Possible mechanisms are inflammation and oxidative stress. Adenotonsillectomy in childhood obesity is associated with a high recurrence rate and risk of postoperative weight gain. Therefore, this study assessed the effects of SDB on inflammation and oxidative stress in childhood obesity before and after weight loss. We included 132 obese subjects between 10 and 18 years consecutively. Median age was 15.4 years (10.1-18.0). Mean BMI z-score was 2.72 ± 0.42. Leukocytes and differentiation, high sensitivity C-reactive protein (hs-CRP), and uric acid (UA) were determined at baseline and subjects underwent a sleep assessment. SDB was diagnosed in 39%. Linear regression analysis showed an association between UA(log) and oxygen desaturation index(log) (ODI(log)) (r = 0.20; P = 0.03), between leukocytes(log) and respiratory disturbance index(log) (RDI(log)) (r = 0.23; P = 0.01), and between lymphocytes(log) and RDI(log) (r = 0.19; P = 0.04). Follow-up was organized after 4-6 months of treatment. Median decrease in BMI z-score was 32%. Laboratory measurements were repeated. Subjects with SDB at baseline underwent a second sleep study. Of these 49 subjects, 12 showed residual SDB. This corresponds with a treatment success rate of 71%. Unlike changes in inflammatory markers, improvements in UA were associated with improvements in RDI and ODI (respectively: r = 0.44; P = 0.007, r = 0.41; P = 0.01). In conclusion, weight loss is effective in treating obese children with SDB. At baseline, a link exists between inflammation and SDB. Oxidative stress is reflected by UA at baseline and the concentration decreases after treatment according to improvements in SDB.     

Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long‐term Weight Gain

We have examined the relationship between artificially sweetened beverage (ASB) consumption and long-term weight gain in the San Antonio Heart Study. From 1979 to 1988, height, weight, and ASB consumption were measured among 5,158 adult residents of San Antonio, Texas. Seven to eight years later, 3,682 participants (74% of survivors) were re-examined. Outcome measures were incidence of overweight/obesity (OW/OB(inc)) and obesity (OB(inc)) (BMI > or = 25 and > or = 30 kg/m(2), respectively), and BMI change by follow-up (DeltaBMI, kg/m(2)). A significant positive dose-response relationship emerged between baseline ASB consumption and all outcome measures, adjusted for baseline BMI and demographic/behavioral characteristics. Consuming >21 ASBs/week (vs. none) was associated with almost-doubled risk of OW/OB (odds ratio (OR) = 1.93, P = 0.007) among 1,250 baseline normal-weight (NW) individuals, and doubled risk of obesity (OR = 2.03, P = 0.0005) among 2,571 individuals with baseline BMIs <30 kg/m(2). Compared with nonusers (+1.01 kg/m(2)), DeltaBMIs were significantly higher for ASB quartiles 2-4: +1.46 (P = 0.003), +1.50 (P = 0.002), and +1.78 kg/m(2) (P < 0.0001), respectively. Overall, adjusted DeltaBMIs were 47% greater among artificial sweetener (AS) users than nonusers (+1.48 kg/m(2) vs. +1.01 kg/m(2), respectively, P < 0.0001). In separate analyses--stratified by gender; ethnicity; baseline weight category, dieting, or diabetes status; or exercise-change category--DeltaBMIs were consistently greater among AS users. These differences, though not significant among exercise increasers, or those with baseline diabetes or BMI >30 kg/m(2) (P = 0.069), were significant in all 13 remaining strata. These findings raise the question whether AS use might be fueling--rather than fighting--our escalating obesity epidemic.     

BMI and Waist Circumference as Predictors of Well‐being in Older Adults: Findings From the English Longitudinal Study of Ageing

The aim of this study is to examine the association of BMI and waist circumference (WC), with a quality of life (QoL) indicator designed for older ages (CASP19), and with depressive symptoms (Centre for Epidemiologic Studies Depression Scale). We included 8,688 individuals aged ≥52 years who participants of Wave 2 (2004–2005) and Wave 3 (2006–2007) of the English Longitudinal Study of Ageing (ELSA). To explore cross‐sectional relationships (2004–2005), we fitted regression models for BMI and WC (included simultaneously) as our predictors of QoL and depressive symptoms adjusted for covariates. To explore longitudinal relationships, BMI and waist at baseline (2004–2005) were related to the each outcome variable measured at follow‐up (2006–2007), and adjusted for baseline characteristics (2004–2005). For a given BMI, larger WC was associated with lower QoL and higher risk of depressive symptoms for women in cross‐sectional and longitudinal analyses. By contrast for a given WC increased BMI for women was positively associated with QoL and lower odds of depressive symptoms. In men, for a given BMI, increased WC was related to QoL only cross‐sectionally; neither WC nor BMI at baseline were associated with depressive symptoms (cross‐sectionally or longitudinally). In conclusion among older people, for a given BMI, increased WC was related with higher risk of poor QoL and, for women, of depressive symptoms; whereas for a given WC, increased BMI had a protective effect on QoL for women.     

Lifestyle intervention leading to moderate weight loss normalizes postprandial triacylglycerolemia despite persisting obesity

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.