No Modulation of the Effect of Aspirin by Body Weight in Healthy Older Men and Women.
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ABSTRACT:
SUBMITTER: Woods RL
PROVIDER: S-EPMC7286412 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPAR?-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
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Project description:ObjectiveWeight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults.Research design and methodsParticipants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed.ResultsBody weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05).ConclusionsLifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors.
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Project description:Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NF?B signaling and Wnt/?-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21-45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed.
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Project description:Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.
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Project description:How different measures of adiposity are similarly or differentially related to mobility limitation and mortality is not clear. In total, 5849 community-dwelling men aged ≥65 years (mean age: 72 years) were followed mortality over 10 years and self-reported mobility limitations (any difficulty walking 2-3 blocks or with climbing 10 steps) at six contacts over 14 years. Baseline measures of adiposity included weight, BMI and percent fat by DXA. Appendicular lean mass (ALM, by DXA) was analyzed as ALM/ht2. Proportional hazards models estimated the risk of mortality, and repeated measures generalized estimating equations estimated the likelihood of mobility limitation. Over 10 years, 27.9% of men died; over 14 years, 48.0% of men reported at least one mobility limitation. We observed U-shaped relationships between weight, BMI, percent fat and ALM/ht2 with mortality. There was a clear log-linear relationship between weight, BMI and percent fat with incident mobility limitation, with higher values associated with a greater likelihood of mobility limitation. In contrast, there was a U-shaped relationship between ALM/ht2 and incident mobility limitation. These observational data suggest that no single measure of adiposity or body composition reflects both the lowest risk of mortality and the lowest likelihood for developing mobility limitation in older men.
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Project description:OBJECTIVE:Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women. RESEARCH DESIGN AND METHODS:This was an ancillary study of a 36-month, randomized, double-blind, controlled trial designed to assess the impact of supplementation with 500 microg/day phylloquinone on bone loss. Study participants were older nondiabetic men and women (n = 355; aged 60-80 years; 60% women). The primary outcome of this study was insulin resistance as measured by homeostasis model assessment (HOMA-IR) at 36 months. Fasting plasma insulin and glucose were examined as the secondary outcomes. RESULTS:The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex x treatment interaction P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women. CONCLUSIONS:Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men.
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Project description:Abdominal subcutaneous adipose tissue transcriptomes were analyzed between 11 young and 8 elderly obese men during a lifestyle intervention. Lifestyle intervention: Individuals underwent 8-weeks of calorie-restriction of 20% below their daily energy requirement aerobic combined to two sessions of resistance exercise per weeks.
2021-08-23 | GSE159809 | GEO
Project description:Vastus lateralis Skeletal muscle transcriptomes were analyzed between 13 young and 12 elderly obese men during a lifestyle intervention. Lifestyle intervention: Individuals underwent 8-weeks of calorie-restriction of 20% below their daily energy requirement aerobic combined to two sessions of resistance exercise per weeks.
2021-08-23 | GSE158850 | GEO
Project description:BackgroundInsulin resistance may be present in healthy adults and is associated with poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults.MethodsA cross-sectional analysis of cardiorespiratory fitness, body mass index, and markers of insulin resistance was performed. Study participants were enrolled at the Cooper Clinic in Dallas, Texas. The analysis included 19,263 women and 48,433 men with no history of diabetes or cardiovascular disease. Cardiorespiratory fitness was measured using exercise treadmill testing. Impaired fasting glucose (100-125 mg/dL) and elevated fasting triglycerides (≥150 mg/dL) were used as a markers of insulin resistance.ResultsAmong individuals with normal weight, poor fitness was associated with 2.2-fold higher odds of insulin resistance in women (1.4-3.6; P = .001) and 2.8-fold higher odds in men (2.1-3.6; P <.001). The impact of fitness remained significant for overweight and obese individuals, with the highest risk group being the unfit obese. Among obese women, the odds ratio for insulin resistance was 11.0 for fit women (8.7-13.9; P <.001) and 20.3 for unfit women (15.5-26.5; P <.001). Among obese men, the odds ratio for insulin resistance was 7.4 for fit men (6.7-8.2; P < .001) and 12.9 for unfit men (11.4-14.6; P < .001).ConclusionsIndependent of weight, poor fitness is associated with risk of insulin resistance. Obese individuals, particularly women, may benefit from the greatest absolute risk reduction by achieving moderate fitness.
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Project description:Our study aimed to select factors that affect the rate of early recurrence (up to 3 months) of atrial fibrillation (AF) (ERAF) following pulmonary veins isolation (PVI) in obese women and men. The study comprised 114 patients: 54 women (age: 63.8 ± 6.3, BMI 31 ± 4 kg/m2), and 60 men (age: 60.7 ± 6.7; BMI 31 ± 3 kg/m2) with paroxysmal, persistent and long-standing persistent AF. They had been scheduled to undergo cryoballoon (men n = 30; women n = 30) and radiofrequency (RF) ablation (men n = 30; women n = 24) using the CARTO-mapping. The blood was collected at baseline and 24 h after ablation. The rate of ERAF was comparable after cryoballoon and RF ablation and constituted 18% in women and 22% in men. Almost 70 parameters were selected to perform univariate and multivariate analysis and to create a multivariate logistic regression (MLR) model of ERAF in the obese men and women. The MLR analysis was performed by forward stepwise logistic regression with three variables. It was only possible to create the MLR model for the group of obese men. It revealed a poor predictive value with an unsatisfactory sensitivity of 31%. Men with ERAF: smokers (OR 39.25, 95% CI 1.050-1467.8, p = 0.0021), with a higher ST2 elevation (OR 1.68, 95% CI 1.115-2.536, p = 0.0021) who received dihydropyridine calcium channel blockers (OR 0.042, 95% CI 0.002-1.071, p = 0.0021) less frequently. Our results indicate a complex pathogenesis of ERAF dependent on the patients' gender.
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