IntroductionThis study investigated whether the timing of a 24-h fast influences indicators of glycemic control throughout the duration of the fast or upon refeeding.MethodsTwenty-four adults who have overweight or obesity (13 female, 11 male) completed this randomized crossover study involving three 24-h fasts initiated at either 8:00 am, 1:00 pm, or 6:00 pm followed by a 75 g oral glucose tolerance test (OGTT) which lasted 2 h. Continuous glucose monitors (CGMs) were employed to track interstitial glucose throughout each fast and OGTT. Plasma samples for insulin and glucagon were collected at the beginning and end of each fast, and 30 min post-OGTT. Capillary beta-hydroxybutyrate (BHB) was only measured at the end of the fasting.ResultsThe 24-h fast initiated in the afternoon had lower post-prandial glucose area under the curve (AUC) following a standardized meal and lower mean 24-h glucose levels than the morning or evening fasts (p < 0.0001) which did not differ. Glucose AUC above baseline at the conclusion of a fast was optimal after the morning compared to the afternoon or evening fast (p < 0.0001), though BHB was above the ketosis threshold (≥0.5 mmol/L) at the end of the afternoon and evening fasts but not the morning fast. Insulin and glucagon did not differ at any point (p > 0.05).DiscussionThe timing of a 24-h fast alters glycemic control and metabolic switching. The afternoon fast optimized glycemic outcomes and ketosis, and these effects appear independent of insulin and glucagon. Aligning fasting protocols with circadian rhythms by initiating a 24-h fast in the afternoon may improve metabolic outcomes related to glycemic control during and immediately after the fast.

Background:Proper estimations of resting energy expenditure (REE) are important for developing weight management strategies, but it is unclear which prediction equations best estimate REE for those with severe obesity. Objectives:This validation study tested 11 previously validated REE prediction equations to determine which equations estimate REE with the least bias and most precision in participants with severe obesity. Methods:REE was measured by indirect calorimetry in 632 females and 148 males with severe obesity from the Utah Obesity Study. A literature search was conducted to identify prediction equations designed from, validated, or commonly used in samples with severe obesity. All equations were tested on each participant. Equations were considered unbiased if mean predicted REE did not differ significantly (P > 0.05) from measured values. Bland-Altman plots characterized bias across measured REE values for prediction equations consistent with measured values. Precision was the percentage of the sample where an equation estimate was within 10% of the measured REE. Equations were further assessed within sex and body mass index subgroups. Results:Only the body weight-based Lazzer equations (Lazzer A) and the Horie-Waitzberg equation generated unbiased predictions across all subgroups, with bias values ranging from -68.1 to 71.6 kcal, yet Bland-Altman plots revealed systematic bias, particularly at extreme values of REE. Equations including body composition did not predict better than body weight-based equations, and no single equation predicted best in every subgroup. Precision measurements never rose above 67.8%. Conclusions:Clinicians may benefit from tailoring their choice of REE prediction equation to the specific characteristics of each patient, favoring equations with lower bias and greater precision within relevant subgroups. However, because of the low precision of REE prediction equations and the systematic bias revealed at REE extremes, it is highly recommended to measure REE whenever possible.

OBJECTIVE:This study addressed the paucity of data exploring long-term effects of metabolic and bariatric surgery (MBS)-related weight loss on fitness. METHODS:Data from MBS patients (SURG; n = 82) and comparable non-surgery participants (NSURG; n = 88) were collected from a subset of a prospective trial, the Utah Obesity Study. Fitness was assessed through maximal and submaximal treadmill tests using a modified Bruce protocol. Submaximal exercise tests were performed preceding surgery at baseline and 11.5 years later. A subset (n = 97) of the 170 participants also performed maximal treadmill tests 2 and 6 years after baseline. Weight and BMI were recorded at each visit. Between-group treadmill time comparisons were adjusted for sex and weight. RESULTS:As expected, SURG had lower BMI and weight than NSURG at all follow-up visits (p < 0.0001). Treadmill time, adjusted for sex, baseline treadmill time, and weight over the 11.5-year period, was elevated in surgery compared to non-surgery groups at all follow-up visits (p < 0.01), but the fitness advantage gradually decreased over time. CONCLUSIONS:An initially dramatic fitness benefit achieved with weight loss in MBS patients gradually declined but remained higher than non-surgery counterparts beyond a decade. An emphasis on physical activity may help sustain improved fitness after bariatric surgery.

Zihao Huang, Msc; Xiaodong Zhuang, PhD; Rihua Huang, MD; Menghui Liu, PhD; Xinghao Xu, MD; Ziyan Fan, MD; Rongling Dai, MA; Hansheng Li, MA; Zhenyu Xiong, PhD; Yue Guo, PhD; Qi Liang, PhD; Xinxue Liao, PhD

Background/Objectives: Metabolic and bariatric surgery (MBS) is known to reduce cancer risk. However, the association between specific bariatric procedures and cancer incidence is not well-studied. This study examined the association between four different MBS procedures and cancer incidence. Methods: Bariatric surgery registry data were linked with statewide cancer registry data from 1979 to 2018. The study included 27,092 adult subjects (aged ≥ 18 years old at surgery) who underwent MBS (BMI ≥ 30 kg/m2 at surgery) from 1979 to 2017. Cancer records were linked to MBS patient records, resulting in 1547 cancer cases. Cox proportional hazards regression was used to examine the association between MBS procedure types and cancer incidence. Results: Of all patients, 75% underwent Roux-en-Y gastric bypass (RYGB), 9% adjustable gastric banding (AGB), 10% sleeve gastrectomy (SG), and 6% duodenal switch (BPD-DS). The overall cancer incidence during the follow-up period was 6.4% for RYGB, 4.6% for AGB, 1.6% for SG, and 5.9% for BPD-DS. The mean follow-up duration from surgery to cancer incidence or censoring was 167 months (standard deviation = 121 months). Compared to RYGB, patients who underwent AGB (Hazard Ratio [HR] = 1.26, p = 0.03) and BPD-DS (HR = 1.91, p < 0.01) had a significantly higher hazard of developing cancer, while SG (HR = 1.17, p = 0.33) showed no significant difference. Conclusions: These findings suggest that AGB and BPD-DS may be associated with higher cancer risks compared to RYGB. Additional large population studies are needed to better understand the long-term cancer risks and mechanisms associated with different MBS types.

ABSTRACT Introduction It is uncertain whether aerobic exercise in the form of walking contributes to the preservation or increase in total or regional skeletal muscle mass (SMM). Purpose This study aimed to determine the effects of aerobic exercise on total and regional (upper body verses leg SMM) in male ( n = 105) and female ( n = 133) adults with overweight and obesity. Methods A retrospective analysis of data from four randomized controlled trials. Participants included those who completed the given trial (control, n = 63; intervention, n = 175) and with complete magnetic resonance imaging (MRI) measured adipose tissue and SMM pre- and postintervention. Macronutrient intake was assessed for a subsample of participants. Supervised exercise was performed by walking on a treadmill for durations ranging from 12 to 24 wk at intensities between 50% and 75% of V̇O 2peak . Results All MRI-measured adipose tissue depots were reduced, and cardiorespiratory fitness was increased by aerobic exercise compared with controls ( P < 0.001). Independent of baseline SMM, aerobic exercise was associated with a small reduction (estimated mean difference ± standard error) in whole-body SMM (−0.310 ± 0.150 kg, P = 0.039) and upper body SMM (−0.273 ± 0.121 kg, P = 0.025) compared with control. No between-group difference was observed for change in leg SMM ( P > 0.10). A negative association was observed between the relative change in body weight and change in total ( R 2 = 0.37, P < 0.001), upper body ( R 2 = 0.21, P < 0.001), and leg SMM ( R 2 = 0.09, P = 0.701). The SMM-to-adipose tissue ratio increased in response to aerobic exercise and was positively associated with weight loss ( P < 0.001). Change in SMM was not associated with dietary protein intake ( P > 0.10). Conclusions Aerobic exercise performed while walking preserves, but does not increase, SMM in exercising muscle of adults. SMM not directly targeted by aerobic exercise may not be maintained.

AbstractThe Tour Divide (TD) is a 4385 km ultra‐endurance bicycle race that follows the continental divide from Canada to Mexico. In this case study, we performed a comprehensive molecular and physiological profile before and after the completion of the TD. Assessments were performed 35 days before the start (Pre‐TD) and ∼36 h after the finish (Post‐TD). Total energy expenditure was assessed during the first 9 days by doubly labelled water (2H218O), abdominal and leg tissue volumes via MRI, and graded exercise tests to quantify fitness and substrate preference. Vastus lateralis muscle biopsies were taken to measure mitochondrial function via respirometry, and vascular function was assessed using Doppler ultrasound. The 47‐year‐old male subject took 16 days 7 h 45 min to complete the route. He rode an average of 16.8 h/day. Neither maximal O2 uptake nor maximal power output changed pre‐ to post‐TD. Measurement of total energy expenditure and dietary recall records suggested maintenance of energy balance, which was supported by the lack of change in body weight. The subject lost both appendicular and trunk fat mass and gained leg lean mass pre‐ to post‐TD. Skeletal muscle mitochondrial and vascular endothelial function decreased pre‐ to post‐TD. Overall, exercise performance was maintained despite reductions in muscle mitochondrial and vascular endothelial function post‐TD, suggesting a metabolic reserve in our highly trained athlete.

Objective: This proof-of-concept study was to investigate the relationship between photobiomodulation (PBM) and neuromuscular control.Background: The effects of concussion and repetitive head acceleration events (RHAEs) are associated with decreased motor control and balance. Simultaneous intranasal and transcranial PBM (itPBM) is emerging as a possible treatment for cognitive and psychological sequelae of brain injury with evidence of remote effects on other body systems.Methods: In total, 43 (39 male) participants, age 18-69 years (mean, 49.5; SD, 14.45), with a self-reported history of concussive and/or RHAE and complaints of their related effects (e.g., mood dysregulation, impaired cognition, and poor sleep quality), completed baseline and posttreatment motor assessments including clinical reaction time, grip strength, grooved pegboard, and the Mini Balance Evaluation Systems Test (MiniBEST). In the 8-week interim, participants self-administered itPBM treatments by wearing a headset comprising four near-infrared light-emitting diodes (LED) and a near-infrared LED nasal clip.Results: Posttreatment group averages in reaction time, MiniBEST reactive control subscores, and bilateral grip strength significantly improved with effect sizes of g = 0.75, g = 0.63, g = 0.22 (dominant hand), and g = 0.34 (nondominant hand), respectively.Conclusion: This study provides a framework for more robust studies and suggests that itPBM may serve as a noninvasive solution for improved neuromuscular health.

This study aimed to determine the impact of various fast-interrupting shakes on markers of glycemic control including glucose, β-hydroxybutyrate (BHB), insulin, glucagon, GLP-1, and GIP. Twenty-seven sedentary adults (twelve female, fifteen male) with overweight or obesity completed this study. One condition consisted of a 38-h water-only fast, and the other two conditions repeated this, but the fasts were interrupted at 24 h by either a high carbohydrate/low fat (HC/LF) shake or an isovolumetric and isocaloric low carbohydrate/high fat (LC/HF) shake. The water-only fast resulted in 135.3% more BHB compared to the HC/LF condition (p < 0.01) and 69.6% more compared to the LC/HF condition (p < 0.01). The LC/HF condition exhibited a 38.8% higher BHB level than the HC/LF condition (p < 0.01). The area under the curve for glucose was 14.2% higher in the HC/LF condition than in the water condition (p < 0.01) and 6.9% higher compared to the LC/HF condition (p < 0.01), with the LC/HF condition yielding 7.8% more glucose than the water condition (p < 0.01). At the 25-h mark, insulin and glucose-dependent insulinotropic polypeptide (GIP) were significantly elevated in the HC/LF condition compared to the LC/HF condition (p < 0.01 and p = 0.02, respectively) and compared to the water condition (p < 0.01). Furthermore, insulin, GLP-1, and GIP were increased in the LC/HF condition compared to the water condition at 25 h (p < 0.01, p = 0.015, and p < 0.01, respectively). By the 38-h time point, no differences were observed among the conditions for any of the analyzed hormones. While a LC/HF shake does not mimic a fast completely, it does preserve some of the metabolic changes including elevated BHB and glucagon, and decreased glucose and insulin compared to a HC/LF shake, implying a potential for improved metabolic health.

This cross-sectional investigation examined the relationship between sitting time and insulin resistance in 6931 U.S. adults. The mediating effects of several covariates were evaluated. Self-reported sitting time, measured in minutes per day, was the exposure variable. Insulin resistance (IR), indexed using the natural log of the homeostatic model assessment of insulin resistance (L-HOMA-IR), was the outcome variable. This study used data collected from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Results showed a strong, positive, dose-response association between sitting time and insulin resistance after adjusting for age, sex, race, and year of assessment ( F = 12.6 , p < 0.0001 ). Across the sitting time tertiles (low, moderate, and high), the L-HOMA-IR means (±SE) each differed from each other ( 0.37 ± 0.008 , 0.40 ± 0.012 , and 0.43 ± 0.012 ). Further controlling for cigarette smoking and physical activity did not alter the significance of the relationship. Adding body mass index (BMI) to the demographic covariates weakened the relationship, but it remained significant. However, the association was no longer significant after adjusting for the demographic covariates and waist circumference ( F = 1.1 , p = 0.3349 ). None of the L-HOMA-IR means (±SE) differed from each other ( 0.40 ± 0.007 , 0.41 ± 0.009 , and 0.41 ± 0.008 ). Overall, waist circumference was a powerful mediating variable between sitting time and insulin resistance. Apparently, time spent sitting is a powerful predictor of IR. However, much of the association between sitting time and IR is a function of differences in waist size. As a strong measure of abdominal adiposity and a significant predictor of multiple metabolic diseases, managing waist size is a health practice to consider when insulin resistance is a concern.

Hunger and satiety are controlled by several physiological mechanisms, including pancreatic and gastrointestinal hormones. While the influence of exercise and fasting have been described individually, in relation to these hormones, there is a paucity of work showing the effects of the two modalities (fasting and exercise) combined. Twenty healthy adults (11 males, 9 females) completed both conditions of this study, each consisting of a 36-h water-only fast. One of the fasts began with treadmill exercise, and the differences between the conditions on various appetite hormones were measured every 12 h. The difference in the area under the curve between conditions for ghrelin was 211.8 ± 73.1 pg/mL (F = 8.40, p < 0.0105), and, for GLP-1, it was −1867.9 ± 850.4 pg/mL (F = 4.82, p < 0.0422). No significant differences were noted for areas under the curve between conditions for leptin, PP, PYY, insulin, or GIP. Initiating a fast with exercise lowers ghrelin concentrations and elevates GLP-1 concentrations. Given that ghrelin elicits feelings of hunger and GLP-1 signals feelings of satiety, adding exercise to the beginning of a fast may reduce some of the biological drive of hunger, which could make fasting more tolerable, leading to better adherence and more significant health outcomes.

Obesity is associated with increased cancer risk. Because of the substantial and sustained weight loss following bariatric surgery, postsurgical patients are ideal to study the association of weight loss and cancer.

Telomere length is a good index of cellular aging. Longer telomeres are predictive of longer life, and healthy lifestyles are associated with longer telomeres. This study explored the relationship between time spent jogging or running each week and leukocyte telomere length (LTL) in 4458 randomly selected U.S. adults. The association was studied using data collected by the National Health and Nutrition Examination Survey (NHANES), and a cross-sectional design. Total weekly jog/run time was calculated from survey responses. From the minute totals, three categories were formed: <10 min/week, 10–74 min/week, and ≥75 min/week. Adults in the third category met the U.S. guidelines. Data were analyzed using one-way ANOVA. Partial correlation was used to adjust for differences in potential mediating factors, including demographic and lifestyle/medical factors. In the total sample, after adjusting for all the potential covariates, mean LTL significantly differed across the three jog/run categories (F = 4.1, p = 0.0272). Specifically, adults who met the guidelines via jogging and/or running had significantly longer telomeres than adults who performed no jogging/running. Adults in the middle category did not differ from the other two categories. A minimum of 75 min of jogging/running weekly is predictive of longer telomeres when compared to adults who do not jog or run regularly.

ObjectiveThis retrospective study incorporated long-term mortality results after different bariatric surgery procedures and for multiple age at surgery groups. MethodsParticipants with bariatric surgery (surgery) and without (non-surgery) were matched (1:1) for age, sex, BMI, and surgery date with a driver license application/renewal date. Mortality rates were compared by Cox regression, stratified by sex, surgery type, and age at surgery. ResultsParticipants included 21,837 matched surgery and non-surgery pairs. Follow-up was up to 40 years (mean [SD], 13.2 [9.5] years). All-cause mortality was 16% lower in surgery compared with non-surgery groups (hazard ratio, 0.84; 95% CI: 0.79-0.90; p < 0.001). Significantly lower mortality after bariatric surgery was observed for both females and males. Mortality after surgery versus non-surgery decreased significantly by 29%, 43%, and 72% for cardiovascular disease, cancer, and diabetes, respectively. The hazard ratio for suicide was 2.4 times higher in surgery compared with non-surgery participants (95% CI: 1.57-3.68; p < 0.001), primarily in participants with ages at surgery between 18 and 34 years. ConclusionsReduced all-cause mortality was durable for multiple decades, for multiple bariatric surgical procedures, for females and males, and for greater than age 34 years at surgery. Rate of death from suicide was significantly higher in surgery versus non-surgery participants only in the youngest age at surgery participants.

The primary purpose of this investigation was to evaluate the relationship between milk-fat intake and obesity, particularly abdominal obesity, in 13,544 U.S. adults. A lesser objective was to measure the degree to which the association was influenced by multiple potential confounding variables. This cross-sectional study used data from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Quantity of milk-fat regularly consumed was the exposure variable. Sagittal abdominal diameter (SAD), a measure of abdominal obesity, and body mass index (BMI) were the outcome variables. Sagittal abdominal diameter is a strong predictor of visceral abdominal fat, when measured by computed tomography, and has been shown to predict cardiometabolic disorders better than BMI. After controlling for age, race, gender, physical activity, leisure computer use and gaming, alcohol habits, and cigarette use, significantly lower BMIs were associated with consistent non-fat and full-fat milk consumption (F = 4.1, p = 0.0063). A significantly lower SAD was associated only with regular consumption of non-fat milk (F = 5.0, p = 0.0019). No significant differences were detected between the other milk-fat groups or milk abstainers. In this nationally representative sample, only 19.6% of adults regularly consumed low-fat milk. In conclusion, consistent non-fat milk intake was predictive of lower levels of abdominal adiposity compared to consumption of higher levels of milk-fat.

Background: Bariatric surgery leads to long-term remission and reduced incidence of diabetes, hypertension, and dyslipidemia. Short-term studies suggest reduction in specific fat depots may be more predictive of health improvement than reduced body mass index (BMI). Visceral, subcutaneous, epicardial, and liver fat, measured 11 years after bariatric surgery, were associated with long-term remission and incidence of diabetes, dyslipidemia, and hypertension. Methods: Fat depots an average of 11 (maximum 14) years after surgery were quantified by noncontrast computed tomography in subjects who did (N = 261; 86% gastric bypass) or did not (N = 243) have bariatric surgery. Multiple regression related fat depots to disease endpoints with and without adjustment for change in BMI and surgical status. Results: Visceral fat was 42% lower, subcutaneous fat 20% lower, epicardial fat 30% lower, and liver-to-spleen density ratio 9% higher at follow-up in the bariatric surgery group compared with the nonsurgery group (all P < 0.01). Higher visceral fat at follow-up exam was significantly associated with reduced remission and increased incidence of diabetes, hypertension, and dyslipidemia. Subcutaneous fat was not associated with disease. The liver-to-spleen ratio was associated with the remission and incidence of hypertriglyceridemia and not with other fat depots. Epicardial fat was related to incidence of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol. Conclusions: Whether or not a patient shows greater long-term diabetes, dyslipidemia, or hypertension remission or incidence after bariatric surgery appears dependent on the amount of fat within specific fat depots measured at follow-up. Furthermore, associations of the three disease endpoints with different fat depots suggest varied fat depot pathology.

ABSTRACT Purpose This study assessed β-hydroxybutyrate (BHB) concentration during a short-term fast and the degree to which an initial bout of exercise influences the rate of ketogenesis. Methods Twenty subjects (11 male, 9 female) completed two 36-h fasts, with one protocol requiring the subject to complete a treadmill exercise session at the beginning of the fast. BHB levels were assessed via portable meter every 2 h, along with mood and hunger ratings. Venipuncture was performed every 12 h. Results The mean (SD) areas under the curve for BHB concentration were 19.19 (2.59) mmol·L−1 (nonexercised) and 27.49 (2.59) mmol·L−1 (exercised), yielding a difference of 8.30 mmol·L−1 between conditions (95% posterior probability interval (PPI), 1.94 to 14.82 mmol·L−1; posterior probability (PP) = 0.99). The mean (SD) times to BHB concentration of 0.5 mmol·L−1 were 21.07 (2.95) h (nonexercised) and 17.5 (1.69) h (exercised), a 3.57-h difference (95% PPI, −2.11 to 10.87 h; PP = 0.89). The differences in area under the curve between conditions were 5.07 μU·mL−1 (95% PPI, −21.64 to 36.18 μU·mL−1; PP = 0.67) for insulin, 97.13 pg·mL−1 (95% PPI, 34.08 to 354.21 pg·mL−1; PP = 0.98) for glucagon, and 20.83 (95% PPI, 4.70 to 24.22; PP = 0.99) for the insulin/glucagon ratio. Conclusions Completing aerobic exercise at the beginning of a fast accelerates the production of BHB throughout the fast without altering subjective feelings of hunger, thirst, stomach discomfort, or mood. Insulin and the insulin/glucagon ratio experience a marked reduction within the first 12 h of fasting and was not altered with exercise. Thus, exercising at the beginning of a fast may improve the metabolic outcomes of fasting.