53 research outputs found

    FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

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    Objective To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. Design Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. Data sources Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. Eligibility criteria for study selection Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. Results We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. Conclusions We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. Systematic review registration PROSPERO CRD42015015969

    Nine months of combined training improves ex vivo skeletal muscle metabolism in individuals with type 2 diabetes

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    Context: Type 2 diabetes (T2D) has features of disordered lipid and glucose metabolism, due in part to reduced mitochondrial content. Objective: Our objective was to investigate effects of different types of exercise on mitochondrial content and substrate oxidation in individuals with T2D (ancillary study of the randomized controlled trial Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes, HART-D). Intervention: T2D individuals were randomized to aerobictraining (AT, n = 12), resistance training (RT, n = 18), combination training(ATRT, n = 12), or nonexercise control (n = 10). Blooddraws, peakoxygen consumption tests, dual-energy x-ray absorptiometry scans and muscle biopsies of vastus lateralis were performed before and after 9 months. Ex vivo substrate oxidations ((CO2)-C-14), mitochondrial content, and enzyme activities were measured. Glycated hemoglobin A(1c) and free fatty acids were also determined. Results: Mitochondrial content increased after RT and ATRT. Octanoate oxidation increased after AT and ATRT, whereas palmitate, pyruvate, and acetate oxidations increased in all exercise groups. Exercise-induced responses in mitochondrial DNA were associated with improvements in peak oxygen consumption, beta-hydroxyacyl-coenzyme A dehydrogenase activity, and palmitate oxidation. Conclusions: Nine months of AT and RT significantly improved most aspects of skeletal muscle mitochondrial content and substrate oxidation, whereas the combination improved all aspects. These exercise responses were associated with clinical improvements, indicating that long-term training, especially combination, is an effective lifestyle therapy for individuals with T2D by way of improving muscle substrate metabolism. (J Clin Endocrinol Metab 98: 1694-1702, 2013

    Angiotensin-converting enzyme inhibitor use by older adults is associated with greater functional responses to exercise

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    Objectives To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. Design Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. Setting Four academic research centers within the United States. Participants Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. Intervention A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). Measurements Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). Results Physical activity significantly improved the adjusted walking speed of ACEi users (P <.001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P <.001) and of persons who used other antihypertensive drugs (P =.005) but not of antihypertensive nonusers (P =.91).The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). Conclusion For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers

    BDNF Val66Met polymorphism as a moderator of exercise enhancement of smoking cessation treatment in anxiety vulnerable adults

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    Background: Exercise interventions facilitate the odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated benefits from exercise. Accordingly, we hypothesized that the efficacy of vigorous-intensity exercise for smoking cessation would be specific to high-anxiety sensitive Val/Val carriers. Methods: Participants were adults (N = 55) of European ancestry who had participated in a randomized controlled trial comparing a smoking cessation program augmented with exercise vs. augmented with a wellness control treatment. In this secondary analysis, growth curve models for point-prevalence abstinence (PPA) and prolonged abstinence (PA) employed for the main outcome analyses were amended to test the moderator effects of the BDNF Val66Met polymorphism. Results: Consistent with prediction, the advantage of exercise over control for PPA was significantly greater among high-anxiety sensitive persons with the Val/Val genotype than for those with the Val/Met genotype. This advantage did not reach statistical significance for PA. Differences in abstinence between the exercise and control interventions among low-anxiety sensitive smokers were not dependent on the BDNF Val66Met polymorphism. Conclusions: We found that the efficacy of exercise for augmenting smoking cessation treatment is intensified among high-anxiety sensitive smokers who are Val/Val carriers. This observation is consistent with findings documenting BDNF mediation of exercise benefits and greater negative affect among smokers who are Val/Val carriers. These data encourage further evaluation of the association between the BDNF polymorphism, exercise, anxiety sensitivity, and smoking cessation

    Anxiety sensitivity and smoking variability among treatment seeking smokers

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    Objectives: Anxiety sensitivity (AS) is associated with poor smoking cessation outcomes. One reason may be that smokers with high AS smoke differently (ie, to manage negative affect and uncomfortable bodily sensations) than other smokers, leading to stronger addiction (due to an affect/sensation based and thereby highly variable rather than a regular smoking routine). Thus, we examined the relationship between AS and smoking variability in a group of treatment-seeking smokers. Methods: Participants (N=136; 52.2% female; Mage=44.19 y, SD=11.29) were daily smokers with elevated AS (AS>=20 on the Anxiety Sensitivity Index 16-item at prescreen) recruited as part of a larger randomized controlled trial for smoking cessation. Most participants were white (73%), educated (with 76% attending some college), unmarried (73%), and employed full-time (56%). They smoked, on average, 17 cigarettes per day. Results: Consistent with prediction, a regression analysis of baseline assessments and a longitudinal analysis with multilevel modeling both showed higher AS was associated with greater variability in cigarettes smoked per day while controlling for sex, age, ethnicity, and income. Conclusions: This finding encourages investigation of how AS might interact with clinical strategies using a fixed smoking taper as part of quit attempts

    Exercise self-efficacy moderates the relation between anxiety sensitivity and body mass index and exercise tolerance in treatment-seeking smokers

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    There is little known about factors that contribute to the comorbidity of cigarette smoking and obesity. The current study sought to test whether exercise self-efficacy moderated the relation between anxiety sensitivity (fear of internal sensations) and BMI and exercise tolerance among cigarette smokers. Smokers (n = 72; 50% female; Mcpd = 19.3, SD = 10.65) were recruited to participate in a smoking cessation treatment trial. During medical screen, we measured weight, height, and exercise tolerance (functional capacity) employing a standardized maximal exercise testing protocol. After adjusting for participant sex and cigarettes per day, exercise self-efficacy moderated the association between anxiety sensitivity and BMI, such that the positive association between anxiety sensitivity and BMI was significantly stronger when exercise self-efficacy was low. The same pattern of results emerged for exercise tolerance. Exercise self-efficacy moderated the association between anxiety sensitivity and exercise tolerance, such that the negative association between anxiety sensitivity and exercise tolerance was significantly stronger when exercise self-efficacy was low. Among smokers, anxiety sensitivity may be a risk variable that, directly and indirectly in the context of low self-efficacy for exercise, causes or maintains higher body weight and lower exercise tolerance
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