Cycling Efficiency During Incremental Cycle Ergometry After 24 Hours of Overfeeding or Fasting.

OBJECTIVE: The objective of this study was to determine whether net cycling efficiency (NET) is altered by 24-hour fasting or overfeeding and whether it correlates with dietary-related energy expenditure (EE) and future weight change. METHODS: In a crossover design, healthy subjects fasted or were overfed for 24 hours while in a whole-room calorimeter using five diets with doubled energy needs: standard, high-carbohydrate (75%), high-fat (60%), high-protein (30%), and low-protein (3%) diets. Graded cycling exercise at low power outputs (10-25-50 W) was performed the day before and after each dietary intervention. RESULTS: NET did not change following any dietary intervention (all P > 0.05 vs. 0). Individual changes in NET did not correlate with EE responses to dietary interventions. However, the change in NET after low-protein overfeeding was inversely correlated with baseline body fat (r = -0.60, P = 0.01); that is, NET increased in lean but decreased in overweight subjects (Δ = 0.010 ± 0.010 vs. -0.013 ± 0.009, P = 0.0003). Increased NET following the low-protein diet was associated with weight gain after 6 months (r = 0.60, P = 0.05). CONCLUSIONS: Despite no substantial effect of acute overfeeding or fasting on NET, the change in NET following low-protein overfeeding depends on adiposity and may influence weight change, suggesting that increased efficiency in a setting of protein scarcity is an adaptive response that may ultimately lead to weight gain.

Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods.

OBJECTIVE: This study sought to understand how the dietary source of carbohydrates, either high-fructose corn syrup (HFCS) or complex carbohydrates, affects energy expenditure (EE) measures, appetitive sensations, and hormones during 24 hours of overfeeding. METHODS: Seventeen healthy participants with normal glucose regulation had 24-hour EE measures and fasting blood and 24-hour urine collection during four different 1-day diets, including an energy-balanced diet, fasting, and two 75% carbohydrate diets (5% fat) given at 200% of energy requirements with either HFCS or whole-wheat foods as the carbohydrate source. In eight volunteers, hunger was assessed with visual analog scales the morning after the diets. RESULTS: Compared with energy balance, 24-hour EE increased 12.8% ± 6.9% with carbohydrate overfeeding (P < 0.0001). No differences in 24-hour EE or macronutrient utilization were observed between the two high-carbohydrate diets; however, sleeping metabolic rate was higher after the HFCS diet (Δ = 35 ± 48 kcal [146 ± 200 kJ]; P = 0.01). Insulin, ghrelin, and triglycerides increased the morning after both overfeeding diets. Urinary cortisol concentrations (82.8 ± 35.9 vs. 107.6 ± 46.9 nmol/24 h; P = 0.01) and morning-after hunger scores (Δ = 2.4 ± 2.0 cm; P = 0.01) were higher with HFCS overfeeding. CONCLUSIONS: The dietary carbohydrate source while overeating did not affect 24-hour EE, but HFCS overconsumption may predispose individuals to further overeating due to increased glucocorticoid release and increased hunger the following morning.

Early results of a surgeon-led, perioperative surgical home.

BACKGROUND: The Perioperative Surgical Home is a novel care model designed to provide patient-centered, high-quality surgical care. In 2013, we implemented POSH, a pilot Peri-Operative Surgical Home at Phoenix Indian Medical Center (PIMC), an Indian Health Service hospital, as a quality improvement project. After 2 y, we sought to quantify the impact of POSH on the quality of surgical care at PIMC. MATERIALS AND METHODS: We conducted a retrospective review of 33 surgical patients who underwent surgery at PIMC through the POSH process between 2013 and 2015 matched to 64 historical controls with similar operations. Study patients underwent surgery via the POSH treatment process. Primary outcomes were composite measures of (1) care standards and (2) care goals. Success was defined as meeting seven of nine care standards and six of eight care goals. RESULTS AND DISCUSSION: The mean number of care standards met was 8.1 ± 1.0 versus 4.2 ± 1.4 (P < 0.001) and the mean number of care goals met was 6.7 ± 0.8 versus 6.1 ± 1.1 (P = 0.005) for POSH patients and historical controls, respectively. Patients participating in the POSH model were 8.6 (95% confidence interval: 3.5-22.3) and 1.5 (95% confidence interval: 1.2-1.9) times more likely to meet the minimum number of care standards and goals, respectively. Fourteen of the study patients (42%) would not have been offered surgery at PIMC before POSH due to elevated surgical risk. CONCLUSIONS: POSH may have improved quality of surgical care at PIMC while expanding services to more complex patients. POSH may present an opportunity for improved surgical quality in resource-constrained environments.

Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation.

OBJECTIVE: To investigate the concurrent relationships between human plasma erythropoietin concentrations and energy expenditure (EE), body composition, plasma leptin concentrations, and associations with weight change. METHODS: Plasma to measure erythropoietin and leptin; data for body composition; 24-h EE measured in a whole-room calorimeter; and 75 g oral glucose tolerance testing were available from 109 full-heritage Pima Indians (55% male) from a larger study designed to understand the causes of obesity. Seventy-nine subjects had data for weight at a later visit (mean follow-up = 4.3 ± 1.9 years) to calculate percent weight change per year. RESULTS: Erythropoietin, adjusted for covariates, correlated with 24-h EE (r = 0.26, P = 0.007), sleeping EE (r = 0.29, P = 0.003), fat-free mass (r = 0.19, P = 0.05), and fat mass (r = 0.27, P = 0.005), but not insulin or glucose measures. The association of erythropoietin with 24-h EE was fully mediated by fat-free mass. Erythropoietin associated with leptin in women (ρ = 0.36, P = 0.01), but not in men (P = 0.9), independently from fat mass. The association of erythropoietin with percent weight change per year was in opposing directions (interaction: P = 0.002) in males (r = -0.35, P = 0.02) versus females (r = 0.37, P = 0.02). CONCLUSIONS: Non-hematopoietic endogenous erythropoietin action may be involved in body weight regulation in opposing directions in men and women, i.e., weight loss in men and weight gain in women.

Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change.

Because it is unknown whether 24-h energy expenditure (EE) responses to dietary extremes will identify phenotypes associated with weight regulation, the aim of this study was to determine whether such responses to fasting or overfeeding are associated with future weight change. The 24-h EE during energy balance, fasting, and four different overfeeding diets with 200% energy requirements was measured in a metabolic chamber in 37 subjects with normal glucose regulation while they resided on our clinical research unit. Diets were given for 24 h each and included the following: (1) low protein (3%), (2) standard (50% carbohydrate, 20% protein), (3) high fat (60%), and (4) high carbohydrate (75%). Participants returned for follow-up 6 months after the initial measures. The decrease in 24-h EE during fasting and the increase with overfeeding were correlated. A larger reduction in EE during fasting, a smaller EE response to low-protein overfeeding, and a larger response to high-carbohydrate overfeeding all correlated with weight gain. The association of the fasting EE response with weight change was not independent from that of low protein in a multivariate model. We identified the following two independent propensities associated with weight gain: a predilection for conserving energy during caloric and protein deprivation and a profligate response to large amounts of carbohydrates.

Higher Daily Energy Expenditure and Respiratory Quotient, Rather Than Fat-Free Mass, Independently Determine Greater ad Libitum Overeating.

CONTEXT: Body fat-free mass (FFM), energy expenditure (EE), and respiratory quotient (RQ) are known predictors of daily food intake. Because FFM largely determines EE, it is unclear whether body composition per se or the underlying metabolism drives dietary intake. OBJECTIVE: The objective of the study was to test whether 24-hour measures of EE and RQ and their components influence ad libitum food intake independently of FFM. DESIGN AND PARTICIPANTS: One hundred seven healthy individuals (62 males/45 females, 84 Native Americans/23 whites; age 33 ± 8 y; body mass index 33 ± 8 kg/m(2); body fat 31% ± 8%) had 24-hour measures of EE in a whole-room indirect calorimeter during energy balance, followed by 3 days of ad libitum food intake using computerized vending machine systems. Body composition was estimated by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FFM, 24-hour EE, RQ, spontaneous physical activity, sleeping EE (sleeping metabolic rate), awake and fed thermogenesis, and ad libitum food intake (INTAKE) were measured. RESULTS: Higher 24-hour RQ (P < .001, partial R(2) = 16%) and EE (P = .01, partial R(2) = 7%), but not FFM (P = .65), were independent predictors of INTAKE. Mediation analysis demonstrated that 24-hour EE is responsible for 80% of the FFM effect on INTAKE (44.5 ± 16.9 kcal ingested per kilogram of FFM, P= .01), whereas the unique effect due to solely FFM was negligible (10.6 ± 23.2, P = .65). Spontaneous physical activity (r = 0.33, P = .001), but not sleeping metabolic rate (P = .71), positively predicted INTAKE, whereas higher awake and fed thermogenesis determined greater INTAKE only in subjects with a body mass index of 29 kg/m(2) or less (r = 0.44, P = .01). CONCLUSIONS: EE and RQ, rather than FFM, independently determine INTAKE, suggesting that competitive energy-sensing mechanisms driven by the preferential macronutrient oxidation and total energy demands may regulate food intake.

Overfeeding over 24 hours does not activate brown adipose tissue in humans.

CONTEXT: Human brown adipose tissue (BAT) is activated with cold exposure, but it is unknown whether overfeeding activates BAT. OBJECTIVE: We determined BAT activation with cold, fasting, and overfeeding and the relationship of BAT activation with future weight change. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Sixteen healthy adults were evaluated during energy balance, fasting, and 24 hours of 200% overfeeding. All subjects had a fluorodeoxyglucose-positron emission tomography (PET) scan after exposure to 16°C to determine cold-induced BAT activity (CIBA). The first six subjects had a second PET scan after 36 hours of fasting to establish the lack of BAT activation at 22°C. The other subjects' second PET scan occurred after 24 hours of overfeeding at 22°C but only if they demonstrated CIBA. Twelve subjects returned at 6 months for reassessment of body composition. MAIN OUTCOME MEASURES: BAT was defined in cool scans as voxels with a standardized uptake value (SUV) of 2.0 or greater and Hounsfield units between -250 and -10. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS: Although 75% of the subjects demonstrated visible CIBA, none had visual BAT activity after overfeeding. CIBA was greater than that observed in the same defined BAT voxels after fasting (n = 6; 2.9 ± 0.5 vs 1.2 ± 0.2; Δ = -1.7; 95% confidence interval -2.4, -1.0 SUV; P < .01). In the second cohort, CIBA was also higher than observed BAT voxel activity after 24 hours overfeeding (n = 8; 3.5 ± 0.7 vs 0.9 ± 0.2; Δ = -2.6; 95% confidence interval -3.2, -1.9 SUV; P < .01). Baseline CIBA negatively correlated with changes in fat mass after 6 months (r = -0.72, P = .009). CONCLUSIONS: BAT may be important in weight regulation unrelated to the response to overeating.

Extent and determinants of thermogenic responses to 24 hours of fasting, energy balance, and five different overfeeding diets in humans.

CONTEXT: Individual variation in the ability to convert excess calories to heat and the effects of dietary macronutrient composition are unclear. OBJECTIVE: Stability and determinants of the energy expenditure (EE) response to overconsumption were assessed. DESIGN, SETTING, AND PARTICIPANTS: Twenty subjects (75% male) with normal glucose regulation were evaluated during 24 hours each of energy balance, fasting, and 5 different diets with 200% energy requirements in a clinical research unit. INTERVENTIONS: Five 1-day overfeeding diets were given in random order: high carbohydrate (75%) and low protein (3%); high carbohydrate and normal protein (20%); high fat (46%) and low protein; high fat (60%) and normal protein; and balanced (50% carbohydrates, 20% protein). MAIN OUTCOME MEASURES: The 24-hour EE, sleeping EE, and thermic effect of food (TEF) during each diet were measured with a metabolic chamber. Appetitive hormones were measured before and after the diets. RESULTS: The EE response to overfeeding exhibited good intraindividual reproducibility. Similar increases above eucaloric feeding in 24-hour EE (mean 10.7 ± 5.7%, P < .001; range 2.9-18.8%) and sleeping EE (14.4 ± 11.3%, P < .001; range 1.0-45.1%) occurred when overfeeding diets containing 20% protein, despite differences in fat and carbohydrate content, but the EE response during overfeeding diets containing 3% protein was attenuated. The percent body fat negatively correlated with TEF during normal protein overfeeding (r = -0.53, P < .01). Fasting peptide YY negatively correlated with TEF (r = -0.56, P < .01) and the increase in sleeping EE (r = -0.54, P < .01) during overfeeding. CONCLUSIONS: There is an intrinsic EE response to overfeeding that negatively associates with adiposity, although it represents a small percentage of consumed calories.

Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor.

Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted.