Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk.

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5 pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations

Effect of a 2 week CPAP treatment on mood states in patients with obstructive sleep apnea: a double-blind trial

Obstructive sleep apnea (OSA) is a common disease with significant medical and psychiatric comorbidities. The literature documenting the effects of continuous positive airway pressure (CPAP) treatment on mood in OSA patients is mixed. We previously observed that 1week of CPAP treatment did not result in improvements in mood beyond those observed in a group treated with placebo-CPAP. This study examined the effect of a 2week CPAP treatment on mood in a placebo-controlled design in OSA patients. Fifty patients with untreated sleep apnea were evaluated by polysomnography and completed the Profile of Mood States (POMS) pre-/post-treatment. The patients were randomized for 2weeks to either therapeutic CPAP or placebo-CPAP (at insufficient pressure). Both the therapeutic CPAP and the placebo-CPAP groups showed significant improvements in POMS total score, tension, fatigue, and confusion. No significant time × treatment effect was observed for either group. We could not show a specific beneficial impact of CPAP treatment on mood in OSA patient

The IL-6 Gene Promoter SNP and Plasma IL-6 in Response to Diet Intervention.

We recently reported that interleukin-6 (IL-6), an inflammatory marker associated with breast pathology and the development of breast cancer, decreases with diet intervention and weight loss in both insulin-sensitive and insulin-resistant obese women. Here, we tested whether an individual's genotype at an IL6 SNP, rs1800795, which has previously been associated with circulating IL-6 levels, contributes to changes in IL-6 levels or modifies the effect of diet composition on IL-6 in these women. We genotyped rs1800795 in overweight/obese women (N = 242) who were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet in a 1-year weight loss intervention study of obesity-related biomarkers for breast cancer incidence and mortality. Plasma IL-6 levels were measured at baseline, 6 and 12 months. At baseline, individuals with a CC genotype had significantly lower IL-6 levels than individuals with either a GC or GG genotype (p < 0.03; 2.72 pg/mL vs. 2.04 pg/mL), but this result was not significant when body mass index (BMI) was accounted for; the CC genotype group had lower BMI (p = 0.03; 32.5 kg/m² vs. 33.6 kg/m²). We did not observe a 2-way interaction of time*rs1800795 genotype or diet*rs1800795 genotype. Our findings provide evidence that rs1800795 is associated with IL-6 levels, but do not support a differential interaction effect of rs1800795 and diet composition or time on changes in circulating IL-6 levels. Diet intervention and weight loss are an important strategy for reducing plasma IL-6, a risk factor of breast cancer in women, regardless of their rs1800795 genotype

Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women.

BackgroundOptimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses.Methods and resultsOverweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin-sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P<0.05). Insulin sensitivity and C-reactive protein levels also improved.ConclusionsWeight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007

The association between lipoprotein-associated phospholipase A2 and cardiovascular disease and total mortality in vascular medicine patients

IntroductionIn some community-based studies, lipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be independently predictive of future fatal and nonfatal cardiovascular disease (CVD) events. We tested the hypothesis that Lp-PLA2 is independently predictive of mortality in high-risk patients from a vascular laboratory.MethodsBetween 1990 and 1994, patients seen in the previous 10 years for noninvasive lower extremity arterial testing were invited to return for a vascular examination of the lower extremities. By medical record review, we identified 2265 eligible patients; of these, 508 returned for interviews, blood collection, and arterial examination and represent those who had survived, could be located, and were willing to participate. The 508 subjects were followed up for an average of 6.7 years until the end of the study period on December 31, 2001. Vital status was ascertained by multiple searches of the Social Security Death Index. The primary outcomes for this study were time to any, CVD, and coronary heart disease (CHD) mortality.ResultsThe mean age was 68.2 years, 88% were men, 87% were non-Hispanic white, 39.1% were diagnosed with peripheral arterial disease only, 9.2% with other CVD only, and 28.5% with both peripheral arterial disease and other CVD. During the entire follow-up period, 299 (59.7%) patients died, 167 from CVD, of which 88 deaths were due to coronary heart disease. With adjustment for CVD risk factors and baseline peripheral arterial disease and other CVD, an increment of one standard deviation in Lp-PLA2 activity was associated with a 40% higher risk for CHD mortality at 5 years of follow-up (P = .04). Additional adjustment for triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol reduced this association to nonsignificance (hazard risk, 1.12).ConclusionIn a vascular laboratory patient population, higher levels of LpPLA2 mass and activity were not significantly associated with total, CVD, or CHD mortality at 5 years of follow-up and after adjustment for traditional CVD risk factors and the presence of PAD and other CVD at baseline. An apparent elevated risk of CHD death associated with elevated Lp-PLA2 was largely explained by associated elevations in lipids and lipoproteins

Latent profile analysis of accelerometer-measured sleep, physical activity, and sedentary time and differences in health characteristics in adult women.

ObjectivesIndependently, physical activity (PA), sedentary behavior (SB), and sleep are related to the development and progression of chronic diseases. Less is known about how rest-activity behaviors cluster within individuals and how rest-activity behavior profiles relate to health. In this study we aimed to investigate if adult women cluster into profiles based on how they accumulate rest-activity behavior (including accelerometer-measured PA, SB, and sleep), and if participant characteristics and health outcomes differ by profile membership.MethodsA convenience sample of 372 women (mean age 55.38 + 10.16) were recruited from four US cities. Participants wore ActiGraph GT3X+ accelerometers on the hip and wrist for a week. Total daily minutes in moderate-to-vigorous PA (MVPA) and percentage of wear-time spent in SB was estimated from the hip device. Total sleep time (hours/minutes) and sleep efficiency (% of in bed time asleep) were estimated from the wrist device. Latent profile analysis (LPA) was performed to identify clusters of participants based on accumulation of the four rest-activity variables. Adjusted ANOVAs were conducted to explore differences in demographic characteristics and health outcomes across profiles.ResultsRest-activity variables clustered to form five behavior profiles: Moderately Active Poor Sleepers (7%), Highly Actives (9%), Inactives (41%), Moderately Actives (28%), and Actives (15%). The Moderately Active Poor Sleepers (profile 1) had the lowest proportion of whites (35% vs 78-91%, p < .001) and college graduates (28% vs 68-90%, p = .004). Health outcomes did not vary significantly across all rest-activity profiles.ConclusionsIn this sample, women clustered within daily rest-activity behavior profiles. Identifying 24-hour behavior profiles can inform intervention population targets and innovative behavioral goals of multiple health behavior interventions

Objectively measured sedentary behavior and quality of life among survivors of early stage breast cancer.

PurposeThis study examined relationships between sedentary behavior accumulated in different bout durations and quality of life (QoL) among breast cancer survivors.MethodsPostmenopausal breast cancer survivors completed the Short Form Health Survey to assess QoL and wore an accelerometer to measure sedentary behavior and physical activity between August 2011 and May 2013.ResultsParticipants (n = 134) averaged 509.7 min/day in sedentary time with 285.2 min/day in short bouts (<20 min) and 224.5 min/day long bouts (≥20 min). Linear regression models indicated that greater total sedentary time was significantly associated with worse physical QoL (b = -0.70, p = 0.02) but not mental QoL (p = 0.92). Models that examined the accumulation of sedentary time in short bouts and long bouts together showed that time in long sedentary bouts was significantly related to physical QoL (b = -0.72, p = 0.02), while time in short bouts was not (p = 0.63). Moderate-to-vigorous intensity physical activity (MVPA) was a significant effect modifier of the relation between time spent in long sedentary bouts and physical QoL (p = 0.028) such that greater time in long bouts was associated with worse physical QoL only among women with lower levels of MVPA.ConclusionsFindings indicate that time spent in long sedentary bouts is associated with worse physical QoL among breast cancer survivors who do not engage in high levels of MVPA. Future research should examine reducing sedentary time as a potential strategy to improve physical QoL

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted