Daytime Sleepiness Is Associated with Lower Cognitive Scores: The Look AHEAD Study.

Background: Daytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may be associated with cognition in older adults. Objectives: We investigated the association between self-reported daytime sleepiness and cognitive function in the Look AHEAD clinical trial. Design: Observational follow-up of a randomized clinical trial of an intensive lifestyle intervention. Setting: Clinic. Participants: Participants (n=1,778) aged 45-76 years at baseline with type 2 diabetes and overweight or obesity. Interventions: Participants were randomized to an intensive lifestyle intervention for weight loss or a control condition of diabetes support and education. Measurements: Participants provided self-reported levels of daytime sleepiness at baseline and years 12-13. Cognitive function was assessed with a neurocognitive battery at years 12-13 and 18-20. Results: Participants who reported having frequent daytime sleepiness (often or always) performed significantly worse than others on the cognitive composite (-0.35; p-value=0.014) after controlling for covariates. When stratified by intervention arm, participants assigned to the intensive lifestyle intervention who reported often/always having daytime sleepiness performed worse on Digit Symbol Coding (-0.63; p-value=0.05) and Trail Making Part-B (-0.56; p-value=0.02) after controlling for covariates. Statistical interactions revealed associations between daytime sleepiness and the following covariates: race and ethnicity, APOE ε4 carrier status, baseline history of cardiovascular disease, and depression. Conclusions: Daytime sleepiness over ~13 years predicted poorer cognitive performance in older individuals who, by virtue of having diabetes and overweight/obesity, are at high risk for sleep disorders and cognitive impairment.

Sleep-obesity relation: underlying mechanisms and consequences for treatment.

Short sleep duration has been associated with obesity in numerous epidemiological studies. However, such association studies cannot establish evidence of causality. Clinical intervention studies, on the other hand, can provide information on a causal effect of sleep duration on markers of weight gain: energy intake and energy expenditure. Herein is an overview of the science related to the impact of sleep restriction, in the context of clinical intervention studies, on energy intake, energy expenditure and body weight. Additionally, studies that evaluate the impact of sleep restriction on weight loss and the impact of sleep extension on appetite are discussed. Information to date suggests that weight management is hindered when attempted in the context of sleep restriction, and the public should be made aware of the negative consequences of sleep restriction for weight regulation.

A sipometer for measuring motivation to consume and reward value of foods and beverages in humans: Description and proof of principle.

New methods, derived from animal work, for measuring food reward value (i.e. reinforcing value of food), and motivation (i.e. strength of desire) to consume, in humans are described and validated. A sipping device (sipometer) was developed that permits access to a liquid food or beverage on two reward schedules: continuous reinforcement (CR) and progressively increasing time spent exerting pressure on a straw (PR-schedule). In addition, a pictorial scale showing a cup, from which the 'amount wanted' could be marked was used to pre-test potential consumption. Intake, time spent sipping, breakpoint, and pressure exerted were the main dependent variables measured. Three pilot experiments were conducted. In Experiment 1, participants (n=8) consumed yogurt shakes after a 1-h or 21-h food deprivation period on both schedules. In Experiment 2, participants (n=8) sham-consumed (i.e. spit out) sweet and non-sweet beverages, utilizing both schedules. In Experiment 3, sham-consuming sweet and non-sweet beverages on both schedules and working for shake on the PR schedule were repeated, after three nights of either habitual sleep or short sleep duration (n=7) in a crossover design. In Experiment 1, participants sipped longer after 21-h vs. 1-h of food deprivation (13±3.0 vs. 8.0±2.1s; p=0.04), on the PR schedule. In Experiment 2, sham-intake (p=0.01) and sipping time (p=0.04) were greater for sweet than non-sweet beverages on the PR schedule and a similar, though not conventionally significant, effect was observed for exerted pressure (p=0.09). In both Experiment 2 and Experiment 3 after habitual sleep, on the PR schedule, cumulative pressure difference between sweet and non-sweet beverage increased with difference in amount wanted in the taste test. In contrast, after short sleep participants were less willing to work for sweet taste as their wanting increased, suggesting that sleep deprivation raises desire, but lowers behavioral output. Taken together these results demonstrate that the sipometer and associated ratings are reliable and useful measures of motivation to consume and reward value in humans. Participants were more motivated to obtain access to sweet beverages, especially when these were better liked than to obtain access to non-sweet beverages.

Sleep and meal-time misalignment alters functional connectivity: a pilot resting-state study.

Delayed sleep and meal times promote metabolic dysregulation and obesity. Altered coordination of sleeping and eating times may impact food-reward valuation and interoception in the brain, yet the independent and collective contributions of sleep and meal times are unknown. This randomized, in-patient crossover study experimentally manipulates sleep and meal times while preserving sleep duration (7.05±0.44 h for 5 nights). Resting-state functional magnetic resonance imaging scans (2 × 5-minute runs) were obtained for four participants (three males; 25.3±4.6 years), each completing all study phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; and late sleep/late meal). Normal mealtimes were 1, 5, 11 and 12.5 h after awakening; late mealtimes were 4.5, 8.5, 14.5 and 16 h after awakening. Seed-based resting-state functional connectivity (RSFC) was computed for a priori regions-of-interest (seeds) and contrasted across conditions. Statistically significant (P<0.05, whole-brain corrected) regionally specific effects were found for multiple seeds. The strongest effects were linked to the amygdala: increased RSFC for late versus normal mealtimes (equivalent to skipping breakfast). A main effect of sleep and interaction with meal time were also observed. Preliminary findings support the feasibility of examining the effects of sleep and meal-time misalignment, independent of sleep duration, on RSFC in regions relevant to food reward and interoception.

Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men.

BACKGROUND: Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations. METHODS: Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a preload containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only. RESULTS: Food intake at the lunch test meal after the MCT preload (Study 2) was (mean±s.e.m.) 532±389 kcal vs 804±486 kcal after LCT (P<0.05). MCT consumption resulted in a lower rise in triglycerides (P=0.014) and glucose (P=0.066) and a higher rise in peptide YY (PYY, P=0.017) and leptin (P=0.036) compared with LCT (combined data). Correlations between differences in hormone levels (glucagon-like peptide (GLP-1), PYY) and differences in food intake were in the opposite direction to expectations. CONCLUSIONS: MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY and insulin.

Sleep restriction increases the neuronal response to unhealthy food in normal-weight individuals.

CONTEXT: Sleep restriction alters responses to food. However, the underlying neural mechanisms for this effect are not well understood. OBJECTIVE: The purpose of this study was to determine whether there is a neural system that is preferentially activated in response to unhealthy compared with healthy foods. PARTICIPANTS: Twenty-five normal-weight individuals, who normally slept 7-9 h per night, completed both phases of this randomized controlled study. INTERVENTION: Each participant was tested after a period of five nights of either 4 or 9 h in bed. Functional magnetic resonance imaging (fMRI) was performed in the fasted state, presenting healthy and unhealthy food stimuli and objects in a block design. Neuronal responses to unhealthy, relative to healthy food stimuli after each sleep period were assessed and compared. RESULTS: After a period of restricted sleep, viewing unhealthy foods led to greater activation in the superior and middle temporal gyri, middle and superior frontal gyri, left inferior parietal lobule, orbitofrontal cortex, and right insula compared with healthy foods. These same stimuli presented after a period of habitual sleep did not produce marked activity patterns specific to unhealthy foods. Further, food intake during restricted sleep increased in association with a relative decrease in brain oxygenation level-dependent (BOLD) activity observed in the right insula. CONCLUSION: This inverse relationship between insula activity and food intake and enhanced activation in brain reward and food-sensitive centers in response to unhealthy foods provides a model of neuronal mechanisms relating short sleep duration to obesity.

Postprandial thermogenesis and substrate oxidation are unaffected by sleep restriction.

BACKGROUND/OBJECTIVES: The extent to which alterations in energy expenditure (EE) in response to sleep restriction contribute to the short sleep-obesity relationship is not clearly defined. Short sleep may induce changes in resting metabolic rate (RMR), thermic effect of food (TEF) and postprandial substrate oxidation. SUBJECTS/METHODS: Ten females (age and body mass index: 22-43 years and 23.4-28 kg m(-2)) completed a randomized, crossover study assessing the effects of short (4 h per night) and habitual (8 h per night) sleep duration on fasting and postprandial RMR and respiratory quotient (RQ). Measurements were taken after three nights using whole-room indirect calorimetry. The TEF was assessed over a 6-h period following consumption of a high-fat liquid meal. RESULTS: Short versus habitual sleep did not affect RMR (1.01±0.05 and 0.97±0.04 kcal min(-1); P=0.23). Fasting RQ was significantly lower after short versus habitual sleep (0.84±0.01 and 0.88±0.01; P=0.028). Postprandial EE (short: 1.13±0.04 and habitual: 1.10±0.04, P=0.09) and RQ (short: 0.88±0.01 and habitual: 0.88±0.01, P=0.50) after the high-fat meal were not different between conditions. TEF was similar between conditions (0.24±0.02 kcal min(-1) in both; P=0.98), as was the ~6-h incremental area under the curve (1.16±0.10 and 1.17±0.09 kcal min(-1) × 356 min after short and habitual sleep, respectively; P=0.92). CONCLUSIONS: Current findings observed in non-obese healthy premenopausal women do not support the hypothesis that alterations in TEF and postprandial substrate oxidation are major contributors to the higher rate of obesity observed in short sleepers. In exploring a role of sleep duration on EE, research should focus on potential alterations in physical activity to explain the increased obesity risk in short sleepers.

Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes.

Humans have an innate requirement for sleep that is intrinsically governed by circadian and endocrine systems. More recently, reduced sleep duration has gained significant attention for its possible contribution to metabolic dysfunction. Significant evidence suggests that reduced sleep duration may elevate the risk for impaired glucose functioning, insulin resistance and type 2 diabetes. However, to date, few studies have determined the implications of reduced sleep duration with regard to glucose control during pregnancy. With the high prevalence of overweight and obesity in women of reproductive age, the occurrence of gestational diabetes mellitus (GDM) is increasing. GDM results in elevated risk of maternal and fetal complications, as well as increased risk of type 2 diabetes postpartum. Infants born to women with GDM also carry a life-long risk of obesity and type 2 diabetes. The impact of reduced sleep on glucose management during pregnancy has not yet been fully assessed and a paucity of literature currently exits. Herein, we review the association between reduced sleep and impaired carbohydrate metabolism and propose how reduced sleep during pregnancy may result in further dysfunction of the carbohydrate axis. A particular focus will be given to sleep-disordered breathing, as well as GDM-complicated pregnancies. Putative mechanisms of action by which reduced sleep may adversely affect maternal and infant outcomes are also discussed. Finally, we will outline important research questions that need to be addressed.

Phytosterols in nonfat and low-fat beverages have no impact on the LDL size phenotype.

OBJECTIVE: To examine the impact of nonfat and low-fat phytosterol-enriched beverages on low-density lipoprotein (LDL) electrophoretic characteristics. DESIGN: Double-blind, randomized, crossover, placebo-controlled dietary trial. SETTING: Diets were prepared and consumed at the Mary Emily Clinical Nutrition Research Unit of McGill University. Analyses were performed at the Institute on Nutraceuticals and Functional Foods of Laval University. SUBJECTS AND INTERVENTION: In total, 15 moderately hypercholesterolemic persons consumed each of three experimental diets that each comprised a different beverage: nonfat placebo (NF control), nonfat with phytosterols (NFPS) or low-fat with phytosterols (LFPS). Participants consumed three beverages daily at meal time for a total of 1.8 g of phytosterols per day. Nondenaturing 2-16% polyacrylamide gradient gel electrophoreses were used to characterize LDL size characteristics. RESULTS: The NFPS and LFPS beverage induced no significant changes in several features of the LDL size phenotype compared to the control diet. CONCLUSION: The consumption of phytosterol-supplemented nonfat and low-fat beverages is not associated with clinically meaningful changes in the LDL particle size phenotype.

New bioimpedance analysis system: improved phenotyping with whole-body analysis.

OBJECTIVE: Bioimpedance analysis (BIA) is a potential field and clinical method for evaluating skeletal muscle mass (SM) and %fat. A new BIA system has 8-(two on each hand and foot) rather than 4-contact electrodes allowing for rapid 'whole-body' and regional body composition evaluation. DESIGN: This study evaluated the 50 kHz BC-418 8-contact electrode and TBF-310 4-contact electrode foot-foot BIA systems (Tanita Corp., Tokyo, Japan). SUBJECTS: There were 40 subject evaluations in males (n=20) and females (n=20) ranging in age from 6 to 64 y. BIA was evaluated in each subject and compared to reference lean soft-tissue (LST) and %fat estimates in the appendages and remainder (trunk+head) provided by dual-energy X-ray absorptiometry (DXA). Appendicular LST (ALST) estimates from both BIA and DXA were used to derive total body SM mass. RESULTS: The highest correlation between total body LST by DXA and impedance index (Ht(2)/Z) by BC-418 was for the foot-hand segments (r=0.986; left side only) compared to the arm (r=0.970-0.979) and leg segments (r=0.942-0.957)(all P<0.001). The within- and between-day coefficient of variation for %fat and ALST evaluated in five subjects was <1% and approximately 1-3.7%, respectively. The correlations between 8-electrode predicted and DXA appendicular (arms, legs, total) and trunk+head LST were strong and highly significant (all r> or =0.95, P<0.001) and group means did not differ across methods. Skeletal muscle mass calculated (Kim equation) from total ALST by DXA (X+/-s.d.)(23.7+/-9.7 kg) was not significantly different and highly correlated with BC-418 estimates (25.2+/-9.6 kg; r=0.96, P<0.001). There was a good correlation between total body %fat by 8-electrode BIA vs DXA (r=0.87, P<0.001) that exceeded the corresponding association with 4-electrode BIA (r=0.82, P<0.001). Group mean segmental %fat estimates from BC-418 did not differ significantly from corresponding DXA estimates. No between-method bias was detected in the whole body, ALST, and skeletal muscle analyses. CONCLUSIONS: The new 8-electrode BIA system offers an important new opportunity of evaluating SM in research and clinical settings. The additional electrodes of the new BIA system also improve the association with DXA %fat estimates over those provided by the conventional foot-foot BIA.

Added thermogenic and satiety effects of a mixed nutrient vs a sugar-only beverage.

OBJECTIVE: To examine the effects of a sugar-only (SO) beverage vs one containing a mixed-nutrient (MN) composition on energy expenditure and feelings of hunger and satiety. HYPOTHESIS: A beverage containing a mixed macronutrient composition will lead to greater thermic effect of food and feelings of fullness than an isocaloric beverage containing only sugar. RESEARCH METHODS AND PROCEDURES: Adults were randomly assigned to receive a 2510 kJ (600 kcal) SO liquid formula followed by an isovolumic, isoenergetic, MN liquid formula with an energy distribution of 17% protein, 67% carbohydrates as sucrose and corn syrup solids, and 16% fat, or vice versa, in a crossover design. The carbohydrate source in the two beverages was identical: 1:1 ratio of sucrose and corn syrup solids (25 dextrose equivalents). The thermic response was calculated as the 7 h deviation from resting metabolic rate (RMR). Subjects provided hunger/satiety ratings and other related information by visual analog scales at regular intervals throughout the study period. RESULTS: In all, 20 subjects completed the protocol; one was removed from the thermic effect analysis due to discrepant RMRs. Following beverage ingestion, SO and MN liquid meals produced 7 h thermic effects of (X+/-s.e.m.) 274.1+/-27.6 kJ (65.5+/-6.6 kcal) and 372.0+/-33.9 kJ (88.9+/-8.1 kcal), respectively, resulting in a significant (P<0.01) difference between meals (Delta=97.9+/-35.1 kJ [23.4+/-8.4 kcal]). Analysis of satiety ratings using area under the curve analysis showed greater feelings of satiety (P<0.05) with MN compared to SO consumption. Also, subjects felt that they could eat less (P<0.05) after consumption of the MN vs SO beverage. DISCUSSION: In comparison to MN beverages, SO beverages are associated with a relatively high-energy retention without accompanying subjective hunger/fullness compensations, suggesting a basis for their role in long-term unintentional weight gain in healthy adults.

Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue.

OBJECTIVE: Medium-chain triglyceride (MCT) consumption has been shown to increase energy expenditure (EE) and lead to greater losses of the adipose tissue in animals and humans. The objective of this research was to examine the relationship between body composition and thermogenic responsiveness to MCT treatment. DESIGN: Randomized, crossover, controlled feeding trial, with diets rich in either MCT or long-chain triglyceride (LCT) (as olive oil) for periods of 4 weeks each. SUBJECTS: A total of 19 healthy overweight men aged (x+/-s.e.m.) 44.5+/-2.5 y with a body mass index of 27.8+/-0.5 kg/m(2). MEASUREMENTS: EE and body composition were measured using indirect calorimetry and magnetic resonance imaging, respectively, at the baseline and end point of each feeding period. EE was measured for 30 min before consumption of a standard meal and for 5.5 h following the meal. RESULTS: Body weight (BW) decreased (P<0.05) by 1.03+/-0.25 kg with MCT consumption compared to 0.62+/-0.29 kg with LCT consumption. The difference in average EE between MCT and LCT consumptions was related to initial BW, such that men with lower initial BW had a greater rise in EE with MCT consumption relative to LCT on day 28 (r=-0.472, P=0.04) but not day 2 (r=-0.368, P=0.12). Similar results were obtained with fat oxidation on day 28 (r=-0.553, P=0.01). The greater rise in fat oxidation with MCT compared to LCT consumption on day 2 tended to be related to greater loss of BW after MCT vs LCT consumption (r=-0.4075, P=0.08). CONCLUSION: These data suggest that shunting of dietary fat towards oxidation results in diminished fat storage, as reflected by the loss of BW and subcutaneous adipose tissue. Furthermore, MCT consumption may stimulate EE and fat oxidation to a lower extent in men of greater BW compared to men of lower BW, indicative of the lower responsiveness to a rapidly oxidized fat by overweight men.International

Medium- versus long-chain triglycerides for 27 days increases fat oxidation and energy expenditure without resulting in changes in body composition in overweight women.

OBJECTIVE: To determine the effects of long-term consumption of medium chain (MCT) versus long chain triglycerides (LCT) on energy expenditure (EE), substrate oxidation and body composition. HYPOTHESIS: MCT consumption will not result in greater EE, substrate oxidation, and body weight loss compared with LCT consumption. RESEARCH METHODS AND PROCEDURES: Seventeen healthy obese women participated in this randomized, crossover inpatient trial. Meals were prepared and consumed on site for two periods of 27 days. Diets containing 40% of energy as fat, with treatment fat comprising 75% of the total fat, were designed to supply each subject with their individual weight-maintaining energy needs. The MCT diet contained 67% of treatment fat as MCT oil (49% octanoate, 50% decanoate) whereas the LCT diet contained exclusively beef tallow as treatment fat. Body composition was assessed by magnetic resonance imaging (MRI) on day 1 and 28 of each phase while energy expenditure was measured on day 2 and 27. RESULTS: Changes in total and subcutaneous adipose tissue volumes following consumption of MCT and LCT were not different (-0.61+/-0.38 l vs -0.54+/-0.48 l and -0.58+/-0.35 l vs -0.48+/-0.40 l, respectively). Average EE and fat oxidation were greater (P<0.05) during MCT than LCT consumption (0.95+/-0.019 vs 0.90+/-0.024 kcal/min, respectively, for EE and 0.080+/-0.0026 vs 0.075+/-0.0022 g/min, respectively for fat oxidation). DISCUSSION: These results show that long-term consumption of MCT enhances EE and fat oxidation in obese women, when compared to LCT consumption. The difference in body composition change between MCT and LCT consumption, although not statistically different, was consistent with differences predicted by the shifts in EE. It can be concluded that substitution of MCT for LCT in a targeted energy balance diet may prevent long-term weight gain via increased EE.

Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism.

The objective of this article was to review existing literature concerning the effects and mechanisms of action of fermented dairy products on serum cholesterol concentrations. Although not without exception, existing evidence from animal and human studies suggests a moderate cholesterol-lowering action of fermented dairy products. Mechanistically, fermented milk has been shown to cause an increase in human gut bacterial content. These bacteria, once resident in the large intestine, are believed to ferment food-derived indigestible carbohydrates. Such fermentation causes increased production of short-chain fatty acids, which decreases circulatory cholesterol concentrations either by inhibiting hepatic cholesterol synthesis or by redistributing cholesterol from plasma to the liver. Furthermore, increased bacterial activity in the large intestine results in enhanced bile acid deconjugation. Deconjugated bile acids are not well absorbed by the gut mucosa and are excreted. Consequently, cholesterol, being a precursor of bile acids, is utilized to a greater extent for de novo bile acid synthesis. These actions combined are proposed as contributing mechanisms to the association of fermented milk consumption with decreased circulating cholesterol concentrations.