The use of accelerometers to improve estimation of the thermic effect of food in whole room calorimetry studies.

We tested whether spontaneous physical activity (SPA) from accelerometers could be used in a whole-room calorimeter to estimate thermic effect of food (TEF). Eleven healthy participants (63% female; age: 27 ± 4 years; body mass index: 22.8 ± 2.6 kg/m2) completed two 23-hour visits in randomized order: one 'fed' with meals provided and one 'fasted' with no food. SPA was measured by ActivPAL and Actigraph accelerometers. Measured TEF was calculated as the difference in total daily energy expenditure (TDEE) between fed and fasted visits and compared to three methods of estimating TEF: 1) SPA-adjusted TEF (adjTEF)-difference in TDEE without SPA between visits, 2) Wakeful TEF-difference in energy expenditure obtained from linear regression and basal metabolic rate during waking hours, 3) 24h TEF-increase in TDEE above SPA and sleeping metabolic rate. Measured TEF was 9.4 ± 4.5% of TDEE. adjTEF (difference in estimated versus measured TEF: activPAL: -0.3 ± 3.3%; Actigraph: -1.8 ± 8.0%) and wakeful TEF (activPAL: -0.9 ± 6.1%; Actigraph: -2.8 ± 7.6%) derived from both accelerometers did not differ from measured TEF (all p>0.05). ActivPAL-derived 24h TEF overestimated TEF (6.8 ± 5.4%, p=0.002), while Actigraph-derived 24h TEF was not significantly different (4.3 ± 9.4%, p=0.156). TEF estimations using activPAL tended to show better individual-level agreement (i.e., smaller coefficients of variation). Both accelerometers can be used to estimate TEF in a whole-room calorimeter; wakeful TEF using activPAL is the most viable option given strong group-level accuracy and reasonable individual agreement.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

Background: The median eating duration in the U.S. is 14.75 h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12 weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Methods: Eighty-one adults with overweight or obesity (age 18-50 years, BMI 25-45 kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7 days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Results: Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2 ± 6.9 years, BMI 33.8 ± 5.7 kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p = 0.03). Conclusion: There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12 weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

A Naturalistic Actigraphic Assessment of Changes in Adolescent Sleep, Light Exposure, and Activity Before and During COVID-19.

The majority of high school-aged adolescents obtain less than the recommended amount of sleep per night, in part because of imposed early school start times. Utilizing a naturalistic design, the present study evaluated changes in objective measurements of sleep, light, and physical activity before (baseline) and during the first wave of the COVID-19 pandemic (during COVID-19) in a group of US adolescents. Sixteen adolescents (aged 15.9 ± 1.2 years, 68.8% female) wore an actigraphy monitor for 7 consecutive days during an in-person week of school before the pandemic (October 2018-February 2020) and again during the pandemic when instruction was performed virtually (May 2020). Delayed weekday sleep onset times of 1.66 ± 1.33 h (p < 0.001) and increased sleep duration of 1 ± 0.87 h (p < 0.001) were observed during COVID-19 compared with baseline. Average lux was significantly higher during COVID-19 compared with baseline (p < 0.001). Weekday physical activity parameters were not altered during COVID-19 compared with baseline, except for a delay in the midpoint of the least active 5 h (p value = 0.044). This analysis provides insight into how introducing flexibility into the traditional school schedule might influence sleep in adolescents.

Early time-restricted eating compared with daily caloric restriction: A randomized trial in adults with obesity.

OBJECTIVE: This trial aimed to evaluate the acceptability and efficacy of early time-restricted eating plus daily caloric restriction (E-TRE+DCR) compared with DCR alone within a behavioral weight-loss intervention. METHODS: Participants (n = 81, 69 women, mean [SD] age: 38.0 [7.8] years, BMI: 34.1 [5.7] kg/m2 ) were randomized to E-TRE (10-hour eating window starting within 3 hours of waking) plus DCR or DCR alone (~35% DCR) for 39 weeks. The primary outcome was body weight (measured with digital scale) at week 12. Secondary outcomes measured at week 12 included hemoglobin A1c, lipids, energy intake (photographic food records), physical activity (accelerometry), dietary adherence (questionnaires), and body composition (dual-energy x-ray absorptiometry). Weight and body composition were also assessed at week 39. RESULTS: Mean [SD] weight loss was not different between groups at week 12 (E-TRE+DCR: -6.2 [4.1] kg vs. DCR: -5.1 [3.2] kg) or at week 39 (E-TRE: -4.9 [5.3] kg vs. DCR: -4.3 [5.3] kg). There were no between-group differences in changes in body composition, dietary adherence, energy intake, physical activity, hemoglobin A1c, or lipids at week 12. CONCLUSIONS: E-TRE+DCR was found to be an acceptable dietary strategy, resulting in similar levels of adherence and weight loss compared with DCR alone.

The effects of the COVID-19 pandemic on weight loss in participants in a behavioral weight-loss intervention.

OBJECTIVE: This study aimed to assess the effects of the COVID-19 pandemic on weight loss, physical activity, and sleep in adults with overweight or obesity participating in a 39-week weight-loss intervention. METHODS: Participants (n = 81, 85% female, mean [SD] age 38.0 [7.8] years, BMI 34.1 [5.7] kg/m2 ) were enrolled in 3 separate cohorts. Cohorts 1 and 2 were studied prior to the pandemic (pre-COVID cohorts). Cohort 3 (COVID cohort) transitioned to a virtual intervention at week 6, when "stay-at-home" orders were implemented in Colorado. Weight was assessed at baseline, week 12, and week 39 with clinic scales before the pandemic and home scales during the pandemic. Diet was assessed with Likert scales at weeks 4, 8, and 12. Physical activity and sleep were assessed at baseline and week 12 with actigraphy. RESULTS: Participants in the COVID cohort reported greater dietary adherence (p = 0.004) and lost more weight than those in the pre-COVID cohorts at week 12 (-7.7 [3.3] kg vs. -3.7 [3.0] kg, p < 0.001) and week 39 (-8.5 [4.4] kg vs. -2.8 [4.6] kg, p < 0.001). Energy intake did not differ between cohorts (p = 0.51). The COVID cohort increased both sedentary time while awake and time in bed at night. CONCLUSIONS: Although the pandemic caused disruptions for the COVID cohort, participants still achieved weight loss with continued behavioral support.

Bone Turnover Markers After Six Nights of Insufficient Sleep and Subsequent Recovery Sleep in Healthy Men.

PURPOSE: The goal of this study was to determine the bone turnover marker (BTM) response to insufficient and subsequent recovery sleep, independent of changes in posture, body weight, and physical activity. METHODS: Healthy men (N = 12) who habitually slept 7-9 h/night were admitted to an inpatient sleep laboratory for a baseline 8 h/night sleep opportunity followed by six nights of insufficient sleep (5 h/night). Diet, physical activity, and posture were controlled. Serum markers of bone formation (osteocalcin, PINP) and resorption (ß-CTX) were obtained over 24 h at baseline and on the last night of sleep restriction, and on fasted samples obtained daily while inpatient and five times after discharge over 3 weeks. Maximum likelihood estimates in a repeated measures model were used to assess the effect of insufficient and subsequent recovery sleep on BTM levels. RESULTS: There was no statistically or clinically significant change in PINP (p = 0.53), osteocalcin (p = 0.66), or ß-CTX (p = 0.10) in response to six nights of insufficient sleep. There were no significant changes in BTMs from the inpatient stay through 3 weeks of recovery sleep (all p [Formula: see text] 0.63). On average, body weight was stable during the inpatient stay (Δweight = - 0.55 ± 0.91 kg, p = 0.06). CONCLUSION: No significant changes in serum BTMs were observed after six nights of insufficient or subsequent recovery sleep in young healthy men. Changes in weight and physical activity may be required to observe significant BTM change in response to sleep and circadian disruptions. Clinical Trials Registration Registered at ClinicalTrials.gov (NCT03733483) on November 7, 2018.

Examining the Role of Exercise Timing in Weight Management: A Review.

Many adults cite exercise as a primary strategy for losing weight, yet exercise alone is modestly effective for weight loss and results in variable weight loss responses. It is possible that some of the variability in weight loss may be explained by the time of day that exercise is performed. Few studies have directly compared the effects of exercise performed at different times of the day (i. e., morning versus evening exercise). Results from these existing studies are mixed with some studies demonstrating superior weight and fat mass loss from morning exercise, while other studies have found that evening exercise may be better for weight management. Exercise timing may alter modifiable lifestyle behaviors involved in weight management, such as non-exercise physical activity, energy intake, and sleep. The purpose of this review is to summarize evidence for and against time-of-day dependent effects of exercise on weight management. Although limited, we also review studies that have examined the effect of exercise timing on other lifestyle behaviors linked to body weight regulation. While exercise at any time of day is beneficial for health, understanding whether there is an optimal time of day to exercise may advance personalized treatment paradigms for weight management.

Circadian Rhythm of Substrate Oxidation and Hormonal Regulators of Energy Balance.

OBJECTIVE: The circadian system provides an organism with the ability to anticipate daily food availability and appropriately coordinate metabolic responses. Few studies have simultaneously assessed factors involved in both the anticipation of energy availability (i.e., hormones involved in appetite regulation) and subsequent metabolic responses (such as energy expenditure and substrate oxidation) under conditions designed to reveal circadian rhythmicity. METHODS: Eight healthy adults (four females; age: 28.0 ± 2.3 years; BMI: 24.3 ± 2.9 kg/m2 ) participated in a 26-hour constant routine protocol involving continuous wakefulness with constant posture, temperature, dim light, and hourly isocaloric snacks. Indirect calorimetry was performed every 3 hours for measurement of energy expenditure and substrate oxidation. Subjective hunger was obtained hourly using questionnaires. Saliva and plasma were obtained hourly to assess melatonin (circadian phase marker) and hormones (leptin, ghrelin, and peptide YY). RESULTS: Fat and carbohydrate oxidation was highest in the biological evening and morning, respectively. Subjective hunger ratings peaked during the middle of the biological day. Significant circadian rhythms were identified for ghrelin and peptide YY with peaks in the biological evening and morning, respectively. CONCLUSIONS: These findings support a role for the circadian system in the modulation of nutrient oxidation, subjective measures of appetite, and appetitive hormones.

Appetite-Related Responses to Overfeeding and Longitudinal Weight Change in Obesity-Prone and Obesity-Resistant Adults.

OBJECTIVE: Appetite responses to 3 days of overfeeding (OF) were examined as correlates of longitudinal weight change in adults classified as obesity prone (OP) or obesity resistant (OR). METHODS: OP (n = 22) and OR (n = 30) adults consumed a controlled eucaloric and OF diet (140% of energy needs) for 3 days, followed by 3 days of ad libitum feeding. Hunger and satiety were evaluated by visual analog scales. Ghrelin and peptide YY (PYY) levels were measured during a 24-hour inpatient visit on day 3. Body weight and composition were measured annually for 4.0 ± 1.3 years. RESULTS: Dietary restraint and disinhibition were greater in OP than OR (mean difference: 3.5 ± 1.2 and 3.3 ± 0.9, respectively; P < 0.01) participants, and disinhibition was associated with longitudinal weight change (n = 48; r = 0.35; P = 0.02). Compared with the eucaloric diet, energy intake fell significantly in OR participants following OF (P = 0.03) but not in OP (P = 0.33) participants. Twenty-four-hour PYY area under the curve values increased with OF in OR (P = 0.02) but not in OP (P = 0.17) participants. Furthermore, changes in PYY levels with OF correlated with measured energy intake (r = -0.36; P = 0.01). CONCLUSIONS: Baseline disinhibition and PYY responses to OF differed between OP and OR adults. Dietary disinhibition was associated with 5-year longitudinal weight gain. Differences in appetite regulation may underlie differences in propensity for weight gain.

Later Meal and Sleep Timing Predicts Higher Percent Body Fat.

Accumulating evidence suggests that later timing of energy intake (EI) is associated with increased risk of obesity. In this study, 83 individuals with overweight and obesity underwent assessment of a 7-day period of data collection, including measures of body weight and body composition (DXA) and 24-h measures of EI (photographic food records), sleep (actigraphy), and physical activity (PA, activity monitors) for 7 days. Relationships between body mass index (BMI) and percent body fat (DXA) with meal timing, sleep, and PA were examined. For every 1 h later start of eating, there was a 1.25 (95% CI: 0.60, 1.91) unit increase in percent body fat (False Discovery Rate (FDR) adjusted p value = 0.010). For every 1 h later midpoint of the eating window, there was a 1.35 (95% CI: 0.51, 2.19) unit increase in percent body fat (FDR p value = 0.029). For every 1 h increase in the end of the sleep period, there was a 1.64 (95% CI: 0.56, 2.72) unit increase in percent body fat (FDR p value = 0.044). Later meal and sleep timing were also associated with lower PA levels. In summary, later timing of EI and sleep are associated with higher body fat and lower levels of PA in people with overweight and obesity.

Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss.

The current obesity epidemic is staggering in terms of its magnitude and public health impact. Current guidelines recommend continuous energy restriction (CER) along with a comprehensive lifestyle intervention as the cornerstone of obesity treatment, yet this approach produces modest weight loss on average. Recently, there has been increased interest in identifying alternative dietary weight loss strategies that involve restricting energy intake to certain periods of the day or prolonging the fasting interval between meals (i.e., intermittent energy restriction, IER). These strategies include intermittent fasting (IMF; >60% energy restriction on 2-3 days per week, or on alternate days) and time-restricted feeding (TRF; limiting the daily period of food intake to 8-10 h or less on most days of the week). Here, we summarize the current evidence for IER regimens as treatments for overweight and obesity. Specifically, we review randomized trials of ≥8 weeks in duration performed in adults with overweight or obesity (BMI ≥ 25 kg/m2) in which an IER paradigm (IMF or TRF) was compared to CER, with the primary outcome being weight loss. Overall, the available evidence suggests that IER paradigms produce equivalent weight loss when compared to CER, with 9 out of 11 studies reviewed showing no differences between groups in weight or body fat loss.

Effect of frequent interruptions of sedentary time on nutrient metabolism in sedentary overweight male and female adults.

This study compared 24-h nutrient oxidation responses between a sedentary condition (SED) and a condition in which short 5-min bouts of moderate-intensity physical activity were performed hourly for nine consecutive hours over 4 days (MICRO). To determine whether any shifts in fuel use were due solely to increases in energy expenditure, we also studied a condition consisting of a single isoenergetic 45-min bout of moderate-intensity exercise (ONE). Twenty sedentary overweight or obese adults (10 men/10 women; 32.4 ± 6.3 yr; BMI, 30.6 ± 2.9 kg/m2) completed all three conditions (MICRO, SED, and ONE) in a randomized order. Each condition consisted of a 3-day free-living run-in followed by a 24-h stay in a whole-room calorimeter to measure total energy expenditure (TEE) and substrate utilization. Dietary fat oxidation was also assessed during the chamber stay by administering a [1-13C] oleic acid tracer at breakfast. Energy intake was matched across conditions. Both MICRO and ONE increased TEE relative to SED, resulting in a negative energy balance. HOMA-IR improved in both activity conditions. MICRO increased 24-h carbohydrate oxidation compared with both ONE and SED ( P < 0.01 for both). ONE was associated with higher 24-h total fat oxidation compared with SED, and higher 24-h dietary fat oxidation compared with both SED and MICRO. Differences in substrate oxidation remained significant after adjusting for energy balance. In overweight and obese men and women, breaking up sitting time increased reliance upon carbohydrate as fuel over 24 h, while a single energy-matched continuous bout of exercise preferentially relies upon fat over 24 h. NEW & NOTEWORTHY Insulin sensitivity, as assessed by HOMA-IR, was improved after 4 days of physical activity, independent of frequency and duration of activity bouts. Temporal patterns of activity across the day differentially affect substrate oxidation. Frequent interruptions of sedentary time with short bouts of walking primarily increase 24-h carbohydrate oxidation, whereas an energy-matched single continuous bout of moderate intensity walking primarily increased 24-h fat oxidation.

Associations Among Dietary Fat Oxidation Responses to Overfeeding and Weight Gain in Obesity-Prone and Resistant Adults.

OBJECTIVE: This study tested the hypothesis that 3 days of overfeeding (OF) decreases dietary fat oxidation and predicts longitudinal weight change in adults classified as obesity prone (OP) and obesity resistant (OR) based on self-identification and personal and family weight history. Changes in diurnal profiles of plasma metabolites and hormones were measured to probe mechanisms. METHODS: Adults identified as OP (n = 22; BMI: 23.9  ±  2.4 kg/m2 ) and OR (n = 30; BMI: 20.5  ±  2.2 kg/m2 ) completed 3 days of eucaloric (EU) feeding and 3 days of OF. On day 3, the 24-hour total and dietary fat oxidation was measured using room calorimetry and an oral 14 C tracer. Plasma glucose, insulin, triglycerides, and nonesterified fatty acid (NEFA) concentrations were frequently sampled over 24 hours. Body composition was measured annually for 4.0  ±  1.4 years in a subsample (n = 19 OP and 23 OR). RESULTS: Dietary fat oxidation over 24 hours was not altered by OF versus EU (P = 0.54). Weight gain in OP correlated with lower nocturnal NEFA concentrations during OF (r  = -0.60; P = 0.006) and impaired fuel selection over 24 hours (metabolic inflexibility, wake respiratory quotient-sleep respiratory quotient) (r = -0.48; P  = 0.04). CONCLUSIONS: Short-term OF did not alter dietary fat oxidation. Lower nocturnal NEFA availability and metabolic inflexibility to overfeeding may be factors contributing to weight gain.

Free-Living Responses in Energy Balance to Short-Term Overfeeding in Adults Differing in Propensity for Obesity.

OBJECTIVE: Free-living adaptive responses to short-term overfeeding (OF) were explored as predictors of longitudinal weight change in adults classified as having obesity resistance (OR) or obesity proneness (OP) based on self-identification and personal/family weight history. METHODS: Adults identified as OP (n = 21; BMI: 23.8 ± 2.5 kg/m2 ) and OR (n = 20; BMI: 20.2 ± 2.1 kg/m2 ) completed 3 days of eucaloric feeding (EU; 100% of energy needs) and 3 days of OF (140% of energy needs). Following each condition, adaptive responses in physical activity (PA), total daily energy expenditure, ad libitum energy intake, and energy balance were objectively measured for 3 days in a free-living environment. Body mass and composition were measured annually by using dual-energy x-ray absorptiometry for 5 years. Adaptive responses to OF were correlated with 5-year changes in body mass and composition. RESULTS: Increases in sedentary time correlated with longitudinally measured changes in fat mass (r = 0.34, P = 0.04) in the cohort taken as a whole. Those with OP reduced their levels of PA following OF, whereas those with OR maintained or increased their PA. No other variables were found to correlate with weight gain. CONCLUSIONS: Failure to decrease sedentary behavior following short-term OF is one mechanism that may be contributing to fat mass gain.

Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males.

Hypogonadism in males is associated with increased body fat and altered postprandial metabolism, but mechanisms remain poorly understood. Using a cross-over study design, we investigated the effects of short-term sex hormone suppression with or without testosterone add-back on postprandial metabolism and the fate of dietary fat. Eleven healthy males (age: 29 ± 4.5 year; BMI: 26.3 ± 2.1 kg/m2 ) completed two 7-day study phases during which hormone levels were altered pharmacologically to produce a low sex hormone condition (gonadotropin releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a testosterone add-back condition (testosterone gel). Following 7 days of therapy, subjects were administered an inpatient test meal containing 50 µCi of [1-14 C] oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation (14 CO2 in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal. Abdominal and femoral adipose biopsies were taken 24 h after the test meal to determine uptake of the labeled lipid. Postprandial glucose, insulin, free-fatty acid, and triglyceride responses were not different between conditions (P > 0.05). Whole-body energy metabolism was also not different between conditions at any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the relative uptake of 14 C labeled lipid into femoral adipose tissue was greater (P = 0.03) in the low hormone condition. Short-term hormone suppression did not affect energy expenditure or postprandial metabolism, but contributed to greater relative storage of dietary fat in the femoral depot. ClinicalTrials.gov Identifier: NCT03289559.

Sedentary behaviour is a key determinant of metabolic inflexibility.

Metabolic flexibility is defined as the ability to adapt substrate oxidation rates in response to changes in fuel availability. The inability to switch between the oxidation of lipid and carbohydrate appears to be an important feature of chronic disorders such as obesity and type 2 diabetes. Laboratory assessment of metabolic flexibility has traditionally involved measurement of the respiratory quotient (RQ) by indirect calorimetry during the fasted to fed transition (e.g. mixed meal challenge) or during a hyperinsulinaemic-euglycaemic clamp. Under these controlled experimental conditions, 'metabolic inflexibility' is characterized by lower fasting fat oxidation (higher fasting RQ) and/or an impaired ability to oxidize carbohydrate during feeding or insulin-stimulated conditions (lower postprandial or clamp RQ). This experimental paradigm has provided fundamental information regarding the role of substrate oxidation in the development of obesity and insulin resistance. However, the key determinants of metabolic flexibility among relevant clinical populations remain unclear. Herein, we propose that habitual physical activity levels are a primary determinant of metabolic flexibility. We present evidence demonstrating that high levels of physical activity predict metabolic flexibility, while physical inactivity and sedentary behaviours trigger a state of metabolic 'inflexibility', even among individuals who meet physical activity recommendations. Furthermore, we describe alternative experimental approaches to studying the concept of metabolic flexibility across a range of activity and inactivity. Finally, we address the promising use of strategies that aim to reduce sedentary behaviours as therapy to improve metabolic flexibility and reduce weight gain risk.

Ability to adjust nocturnal fat oxidation in response to overfeeding predicts 5-year weight gain in adults.

OBJECTIVE: To determine whether metabolic responses to short-term overfeeding predict longitudinal changes in body weight. METHODS: Twenty-four-hour energy expenditure (EE) and substrate utilization were measured at baseline in a room calorimeter following 3 days of eucaloric and hypercaloric feeding (40% excess) in a sample of lean adults (n: 34; age: 28 ± 2 y; BMI: 22 ± 3 kg/m2 ). Body mass and fat mass (dual-energy x-ray absorptiometry) were measured annually for 5 years. Regression analyses examined whether changes in EE and fuel use with overfeeding predicted body weight and composition changes over 5 years. RESULTS: Overfeeding increased EE and reduced fat oxidation when examined over the 24-hour, waking, and nocturnal periods. Absolute change in body mass over 5 years was 3.0 ± 0.6 kg (average rate of change = 0.7 ± 0.1 kg/y, P < 0.001). Lower nocturnal (but not 24-hour or waking) fat oxidation (r = -0.42, P = 0.01) and EE (r = -0.33, P = 0.05) with overfeeding were the strongest predictors of 5-year weight gain. When adjusted for covariates, changes in nocturnal fat oxidation and EE with overfeeding predicted 41% of the variance in weight change (P = 0.02). CONCLUSIONS: Failure to maintain fat oxidation at night following a period of overfeeding appears to be associated with a metabolic phenotype favoring weight gain.

Endothelial function following glucose ingestion in adults with prediabetes: Role of exercise intensity.

OBJECTIVE: To determine whether high intensity exercise (HIE) would improve endothelial function more than an isocaloric bout of moderate intensity exercise (MIE) following glucose ingestion in adults with prediabetes. METHODS: Twelve subjects with prediabetes completed all three conditions: time-course matched control and isocaloric exercise (∼200 kcal) at moderate (MIE; at lactate threshold) and high intensity (HIE; 75% of difference between lactate threshold and VO2 peak). Brachial artery flow-mediated dilation (FMD) was measured before exercise (baseline), within 30 min postexercise, and 1 and 2 hr following a 75 g oral glucose tolerance test (OGTT). Plasma F2-isoprostanes were also assessed during the protocol (i.e., baseline to 2 hr OGTT) as a biomarker of oxidative stress. RESULTS: MIE reduced postexercise F2-isoprostanesAUC compared with time-course matched control and HIE. Although exercise had no statistical effect on FMD postexercise or during the OGTT, elevations in FMDAUC after MIE and HIE were associated with reduced postexercise F2-isoprostanesAUC . CONCLUSIONS: Exercise at either intensity had no effect on FMD immediately postexercise following glucose administration. However, individuals with reduced oxidative stress responses to exercise had greater exercise-induced improvement in FMD. Further work is required to identify the mechanism by which exercise alters oxidative stress to enhance endothelial function.

Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance.

Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes.