- Email: [email protected]
Effect of Liraglutide on Gastric Emptying at 5 and 16 Weeks: A Single-Center, Randomized, Placebo-Controlled Trial in 32 Patients
weeks, suggesting there is tachyphylaxis in the slowing of gastric emptying on liraglutide treatment. Support: NIH R01-DK67071
the minus sign in ∆ GE T1/2 at 16 wks vs 5 wks reflects slower GE at 5 wks; *p<0.01; **p= 0.046; #p=0.0182 vs placebo (analysis using baseline GE T1/2 as covariate); $p=0.021 for ∆ GE at 16 wks vs 5 wks in liraglutide group by paired t-test
322 ASSOCIATION OF PHYSICAL ACTIVITY WITH FOOD INTAKE, GASTRIC EMPTYING AND GHRELIN LEVELS IN OBESITY Judith Davis, Michael Camilleri, Hoda C. Kadouh, Deborah J. Eckert, Jessica O'Neill, Duane Burton, Andres J. Acosta Cardenas Background: Rapid gastric emptying, increased food intake, and alterations in gastrointestinal hormones are associated with obesity (PMID: 25486131). Physical activity (PA) is recommended alone or in conjunction with diet for the treatment of obesity. Acute and chronic exercise produces a partial compensatory increase in food intake to match the energy expenditure (PMID: 21346335); however, knowledge about the mechanisms behind this metabolic adaptation is very limited. The effects of regular PA on food intake, gastric emptying, gastric accommodation and gastric hormones in adults with obesity remain unclear. Aim: To examine the difference in weight trends, eating behavior, gastric emptying and gastrointestinal hormone levels among overweight and obese individuals who engage in regular PA versus those who do not. Methods: 270 overweight or obese participants (age 37.7±0.72y, 70% females, 91% Caucasian, BMI 33.01±0.3kg/m2) underwent, on different days, validated measurements of GI phenotypes: gastric emptying (GE) of solids and liquids by scintigraphy, gastric volume (GV) by SPECT during fasting and after consumption of 200mL Ensure® (∆ GV), satiety by kcal intake (T-kcal) during a buffet meal, satiation [volume to fullness (VTF) and maximal tolerated volume (MTV)] by Ensure® ingested at 30ml/min, and fasting and postprandial (15, 45 and 90 min) GLP-1, PYY, CCK, and ghrelin (by radioimmunoassay). Physical Activity Stages of Change Questionnaire (PMID: 18243406) was used to assess regular PA (few times weekly for more than 6 months). We assessed the difference between regular PA and physical inactivity in each variable using a t-test. Results (table): PA was associated with lower BMI (mean ∆ 2.01kg/m2, p=0.0011) and body weight (mean ∆ 4.42kg, p=0.0278) when compared to physical inactivity. Gastric emptying of solids (T-lag mean ∆ 2.35min, p=0.0348; T-50% mean ∆ 7.54min, p=0.0206) and liquids (T-50% mean ∆ 2.99min, p=0.0287%) was significantly more rapid in physically active participants. PA was also associated with higher postprandial ghrelin AUC (mean ∆ 10.4pg/ ml, p=0.0150). There were no significant differences in postprandial satiation symptoms, satiety test, gastric volume and accommodation, and satiation GI hormones (CCK, PYY, or GLP-1) between groups. Conclusions: Physical activity keeps BMI down, despite faster gastric emptying and higher (less suppressed) postprandial ghrelin. These findings may explain the compensatory increase in food intake and metabolic adaptation seen with physical activity, which may in turn explain the limited effectiveness of exercise-only weight loss programs for obesity. These data serve to address hypotheses for future studies examining the role of physical activity on gastric functions and satiety-related hormones. Support: NIH R01-DK67071
321 EFFECT OF LIRAGLUTIDE ON GASTRIC EMPTYING AT 5 AND 16 WEEKS: A SINGLE-CENTER, RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN 32 PATIENTS Disha Khemani, Deborah J. Eckert, Jessica O'Neill, Michael Ryks, Deborah Rhoten, Andres J. Acosta Cardenas, Houssam Halawi, Ibironke Oduyebo, Alfred D. Nelson, Duane Burton, Matthew Clark, Alan R. Zinsmeister, Michael Camilleri Background: A subgroup of individuals with obesity has accelerated gastric emptying (solids and liquids, PMID: 25486131). We previously showed that a short-acting GLP-1 agonist, exenatide, 5µg, SQ, BID, for 30 days, delayed gastric emptying and induced weight loss (PMID: 26542264). Gastric emptying was delayed after 3 weeks of treatment with the longeracting GLP-1 agonist, liraglutide, escalated to 1.8mg/day, but there was no difference in gastric emptying relative to baseline after 24 weeks of treatment (PMID: 26656289). Liraglutide, 3mg/day, is the approved dose for treatment of obesity. Aims: To compare gastric emptying of solids after 5 weeks on reaching dose-escalated liraglutide, 3mg/day, and after 12 weeks of full dose liraglutide (total treatment period 16 weeks); and to compare effects of liraglutide with placebo on gastric emptying. Methods: We conducted a randomized, controlled trial of liraglutide and placebo in 40 obese participants (BMI: ≥30kg/m2) with standard liraglutide dose escalation starting at 0.6mg/day and increasing by 0.6mg/day each week for 5 weeks; the highest liraglutide dose reached was maintained over the next 11 weeks. Liraglutide or placebo (saline solution) was self-administered by subcutaneous injection once per day. All participants underwent measurement of gastric emptying of solids by scintigraphy at baseline and after 5 weeks of treatment. Gastric emptying was measured over 4 hours using a 320kcal, 30% fat meal. Statistical analysis examined effect of liraglutide on GE T1/ 2 at 5 and 16 weeks in patients receiving liraglutide (paired t-test), and compared effects of liraglutide with placebo on GE T1/2 at 5 and 16 weeks using ANCOVA with baseline GE T1/2 of solids as a covariate. Results: Four patients dropped out of the study. The median dose of liraglutide at the end of 12 weeks of fully escalated dose in the liraglutide treatment arm was 3mg/day. Liraglutide, 3mg/day, retards gastric emptying of solids at both 5 and 16 weeks relative to effects of placebo. Table shows results (mean+SEM). Conclusion: Liraglutide, 3mg/day, delays gastric emptying of solids at both 5 and 16 weeks relative to effects of placebo. There is, however, faster gastric emptying at 16 weeks compared to 5
Data are mean±SEM; *, statistically significant difference
323 MECHANICALLY INDUCED ENTEROGENESIS OF HUMAN INTESTINAL ORGANOIDS IN VIVO Holly M. Poling, Nicole Brown, David Wu, Nhan Huynh, Simon P. Hogan, James C. Dunn, James Wells, Michael Helmrath, Maxime M. Mahe Background Human Intestinal Organoids (HIOs) generated from embryonic and/or induced pluripotent stem cell lines offer an avenue to study both developmental and human specific disease states. Recently, progress has been made in scaling and maturing these inherently immature tissues through transplanting them in vivo. However, these resultant grafts best
S-83
AGA Abstracts
AGA Abstracts
(p=0.03). Conclusions: The use of obesogenic medications may negatively impact weight loss outcomes post-LSG.
the minus sign in ∆ GE T1/2 at 16 wks vs 5 wks reflects slower GE at 5 wks; *p<0.01; **p= 0.046; #p=0.0182 vs placebo (analysis using baseline GE T1/2 as covariate); $p=0.021 for ∆ GE at 16 wks vs 5 wks in liraglutide group by paired t-test
322 ASSOCIATION OF PHYSICAL ACTIVITY WITH FOOD INTAKE, GASTRIC EMPTYING AND GHRELIN LEVELS IN OBESITY Judith Davis, Michael Camilleri, Hoda C. Kadouh, Deborah J. Eckert, Jessica O'Neill, Duane Burton, Andres J. Acosta Cardenas Background: Rapid gastric emptying, increased food intake, and alterations in gastrointestinal hormones are associated with obesity (PMID: 25486131). Physical activity (PA) is recommended alone or in conjunction with diet for the treatment of obesity. Acute and chronic exercise produces a partial compensatory increase in food intake to match the energy expenditure (PMID: 21346335); however, knowledge about the mechanisms behind this metabolic adaptation is very limited. The effects of regular PA on food intake, gastric emptying, gastric accommodation and gastric hormones in adults with obesity remain unclear. Aim: To examine the difference in weight trends, eating behavior, gastric emptying and gastrointestinal hormone levels among overweight and obese individuals who engage in regular PA versus those who do not. Methods: 270 overweight or obese participants (age 37.7±0.72y, 70% females, 91% Caucasian, BMI 33.01±0.3kg/m2) underwent, on different days, validated measurements of GI phenotypes: gastric emptying (GE) of solids and liquids by scintigraphy, gastric volume (GV) by SPECT during fasting and after consumption of 200mL Ensure® (∆ GV), satiety by kcal intake (T-kcal) during a buffet meal, satiation [volume to fullness (VTF) and maximal tolerated volume (MTV)] by Ensure® ingested at 30ml/min, and fasting and postprandial (15, 45 and 90 min) GLP-1, PYY, CCK, and ghrelin (by radioimmunoassay). Physical Activity Stages of Change Questionnaire (PMID: 18243406) was used to assess regular PA (few times weekly for more than 6 months). We assessed the difference between regular PA and physical inactivity in each variable using a t-test. Results (table): PA was associated with lower BMI (mean ∆ 2.01kg/m2, p=0.0011) and body weight (mean ∆ 4.42kg, p=0.0278) when compared to physical inactivity. Gastric emptying of solids (T-lag mean ∆ 2.35min, p=0.0348; T-50% mean ∆ 7.54min, p=0.0206) and liquids (T-50% mean ∆ 2.99min, p=0.0287%) was significantly more rapid in physically active participants. PA was also associated with higher postprandial ghrelin AUC (mean ∆ 10.4pg/ ml, p=0.0150). There were no significant differences in postprandial satiation symptoms, satiety test, gastric volume and accommodation, and satiation GI hormones (CCK, PYY, or GLP-1) between groups. Conclusions: Physical activity keeps BMI down, despite faster gastric emptying and higher (less suppressed) postprandial ghrelin. These findings may explain the compensatory increase in food intake and metabolic adaptation seen with physical activity, which may in turn explain the limited effectiveness of exercise-only weight loss programs for obesity. These data serve to address hypotheses for future studies examining the role of physical activity on gastric functions and satiety-related hormones. Support: NIH R01-DK67071
321 EFFECT OF LIRAGLUTIDE ON GASTRIC EMPTYING AT 5 AND 16 WEEKS: A SINGLE-CENTER, RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN 32 PATIENTS Disha Khemani, Deborah J. Eckert, Jessica O'Neill, Michael Ryks, Deborah Rhoten, Andres J. Acosta Cardenas, Houssam Halawi, Ibironke Oduyebo, Alfred D. Nelson, Duane Burton, Matthew Clark, Alan R. Zinsmeister, Michael Camilleri Background: A subgroup of individuals with obesity has accelerated gastric emptying (solids and liquids, PMID: 25486131). We previously showed that a short-acting GLP-1 agonist, exenatide, 5µg, SQ, BID, for 30 days, delayed gastric emptying and induced weight loss (PMID: 26542264). Gastric emptying was delayed after 3 weeks of treatment with the longeracting GLP-1 agonist, liraglutide, escalated to 1.8mg/day, but there was no difference in gastric emptying relative to baseline after 24 weeks of treatment (PMID: 26656289). Liraglutide, 3mg/day, is the approved dose for treatment of obesity. Aims: To compare gastric emptying of solids after 5 weeks on reaching dose-escalated liraglutide, 3mg/day, and after 12 weeks of full dose liraglutide (total treatment period 16 weeks); and to compare effects of liraglutide with placebo on gastric emptying. Methods: We conducted a randomized, controlled trial of liraglutide and placebo in 40 obese participants (BMI: ≥30kg/m2) with standard liraglutide dose escalation starting at 0.6mg/day and increasing by 0.6mg/day each week for 5 weeks; the highest liraglutide dose reached was maintained over the next 11 weeks. Liraglutide or placebo (saline solution) was self-administered by subcutaneous injection once per day. All participants underwent measurement of gastric emptying of solids by scintigraphy at baseline and after 5 weeks of treatment. Gastric emptying was measured over 4 hours using a 320kcal, 30% fat meal. Statistical analysis examined effect of liraglutide on GE T1/ 2 at 5 and 16 weeks in patients receiving liraglutide (paired t-test), and compared effects of liraglutide with placebo on GE T1/2 at 5 and 16 weeks using ANCOVA with baseline GE T1/2 of solids as a covariate. Results: Four patients dropped out of the study. The median dose of liraglutide at the end of 12 weeks of fully escalated dose in the liraglutide treatment arm was 3mg/day. Liraglutide, 3mg/day, retards gastric emptying of solids at both 5 and 16 weeks relative to effects of placebo. Table shows results (mean+SEM). Conclusion: Liraglutide, 3mg/day, delays gastric emptying of solids at both 5 and 16 weeks relative to effects of placebo. There is, however, faster gastric emptying at 16 weeks compared to 5
Data are mean±SEM; *, statistically significant difference
323 MECHANICALLY INDUCED ENTEROGENESIS OF HUMAN INTESTINAL ORGANOIDS IN VIVO Holly M. Poling, Nicole Brown, David Wu, Nhan Huynh, Simon P. Hogan, James C. Dunn, James Wells, Michael Helmrath, Maxime M. Mahe Background Human Intestinal Organoids (HIOs) generated from embryonic and/or induced pluripotent stem cell lines offer an avenue to study both developmental and human specific disease states. Recently, progress has been made in scaling and maturing these inherently immature tissues through transplanting them in vivo. However, these resultant grafts best
S-83
AGA Abstracts
AGA Abstracts
(p=0.03). Conclusions: The use of obesogenic medications may negatively impact weight loss outcomes post-LSG.