Women with a low satiety phenotype show impaired appetite control and greater resistance to weight loss.

AbstractThis trial compared weight loss outcomes over 14-weeks in women showing low or high satiety responsiveness [low or high satiety phenotype (LSP, HSP)] measured by a standardized protocol. Food preferences and energy intake after low and high energy density (LED, HED) meals were also assessed. Ninety-six women (n = 52 analysed; 41.24 ± 12.54 years; 34.02 ± 3.58 kg/m2) engaged in one of two weight loss programs underwent LED and HED laboratory-test days during weeks 3 and 12. Preferences for LED and HED-foods (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack energy intake (EI) were assessed in response to equi-caloric LED- and HED-breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the program. Satiety quotients based on subjective fullness ratings post-LED and HED breakfasts determined LSP (n=26) and HSP (n=26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared to HSP. The LSP showed greater preferences for HED-foods, and under HED-conditions, consumed more snacks (kcal) compared to HSP. Snack EI did not differ under LED-conditions. LSP reported less control over eating and reported more difficulty with program adherence. In conclusion, low satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.</jats:p

Free-living energy balance behaviours are associated with greater weight loss during a weight loss programme

Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women. Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared. Results: The energy density of food consumed [β = 0.45, p < 0.001] and vigorous PA [β = −0.30, p < 0.001] early in the intervention (regression model 1) and early-late change in light PA [β = −0.81 p < 0.001], moderate PA [β = −1.17 p < 0.001], vigorous PA [β = −0.49, p < 0.001], total energy expenditure (EE) [β = 1.84, p < 0.001], and energy density of food consumed [β = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04]. Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs

A low energy dense diet in the context of a weight management program improves appetite control in overweight and obese women

Background: Low energy density foods (LED) reduce energy intake (EI); whether this effect is sustained over time and during weight loss is unknown. Objective: This trial examined the effects of LED compared to high energy density (HED) meals on appetite, EI and control over eating in the laboratory and during a weight management program that encourages unrestricted intake of LED foods [Slimming World, UK (SW)] compared to a self-led Standard Care program [NHS weight loss plan (SC)]. Methods: Overweight and obese women (n=96;age:41.03±12.61 years; BMI:34.00±3.61 kg/m2) were recruited from SW- or SC-program. Primary outcomes included appetite, food preferences (liking and wanting for LED and HED foods), cravings and evening meal EI (LED, HED) in response to calorie-matched LED (≤0.8 kcal/g) and HED (≥2.5 kcal/g) breakfast and lunch meals. Probe day tests were conducted at weeks 3 and 4 and repeated at weeks 12 and 13 in a within-day cross-over design. Secondary outcomes including body weight and program experience were measured from week 1 to 14 in a parallel-group design. Dietary compliance was monitored using weighed food diaries at weeks 3 and 12. Results: Intention-to-treat (ITT) and completers-analyses showed SW lost more weight compared to SC [ITT:-5.9% (95%CI:-4.7, -7.2) versus -3.5% (-2.3,-4.8), p<0.05; completers:-6.2% (-4.8,-7.6) versus 3.9% (-2.5,-5.2), p<0.05]. SW reported greater control over eating and more motivation to continue the program compared to SC. LED meals increased sensations of fullness and reduced hunger on probe days (p<0.001). Total-day-EI was 1057±73 kcal less (95% CI:912, 1203;36%) under LED compared to HED (p<.001). Liking for LED and HED foods and wanting for HED foods were lower pre-lunch under LED compared to HED conditions and liking decreased to a greater extent after the LED-lunch. SW reported fewer cravings under LED compared to HED conditions (p<0.05). On probe days, appetite and EI outcomes did not differ between weeks 3 and 12 or SW- and SC-groups. Conclusion: LED meals improve appetite control in women attempting weight loss and the effect is sustainable. Consumption of LED meals likely contributed to weight loss in the SW-program.ClinicalTrials.gov #NCT02012426

Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study

Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers