Examining Weight Suppression, Leptin Levels, Glucagon-Like Peptide 1 Response, and Reward-Related Constructs in Severity and Maintenance of Bulimic Syndromes: Protocol and Sample Characteristics for a Cross-Sectional and Longitudinal Study

Abstract

Background: Bulimia nervosa and related syndromes (BN-S) characterized by binge eating vary considerably in illness severity and course. Using the Research Domain Criteria framework of the National Institute of Mental Health, we developed a model positing that the same set of physiological consequences of weight suppression (WS; defined as the difference between the highest and current adult body weight) contribute to binge-eating severity and maintenance by (1) increasing the drive or motivation to consume food (reward valuation effort [RVE]) and (2) decreasing the ability for food consumption to lead to a state of satiation or satisfaction (reward satiation).

Objective: Our funded project aimed to test concurrent associations among WS, physiological factors (leptin concentrations and postprandial glucagon-like peptide 1 [GLP-1] response), behavioral indicators of RVE (breakpoint on progressive ratio tasks) and reward satiation (ad-lib test meal intake), self-report of these core constructs, and binge-eating severity in BN-S (aim 1); test prospective associations to determine whether WS predicts BN-S maintenance in longitudinal models and whether posited mediators also predict BN-S maintenance (aim 2); and determine whether associations between WS and BN-S severity and maintenance are mediated by alterations in leptin levels, GLP-1 response, RVE, and reward satiation (aim 3).

Methods: We aimed to recruit a sample of 320 women with BN-S or noneating disorder controls, with BMI from 16 kg/m² to 35 kg/m², for our study. The study included diagnostic interviews; questionnaires; height, weight, and percentage of body fat measurements; weight history; fasting leptin level; postprandial GLP-1 and insulin responses to a fixed meal; and ad-lib meal and progressive ratio tasks to behaviorally measure reward satiation and RVE, respectively, at baseline, with at least 78.1% (250/320) of the participants providing data at 6- and 12-month follow-up visits. Data will be analyzed using structural equation models to test posited pathways.

Results: Data collection began in November 2016 and ended in April 2023, pausing in-person data collection from March 2020 to February 2021 due to the COVID-19 pandemic. Of 399 eligible women enrolled, 290 (72.7%) provided clinical, behavioral, and biological data at baseline, and 249 (62.4%) provided follow-up data. Measures demonstrated strong psychometric properties.

Conclusions: We seek to identify biobehavioral predictors to inform treatments that target key factors influencing the severity and course of binge eating. These data, supported solely through federal funding, can inform questions emerging from recent interest and controversy surrounding the use of GLP-1 agonists for binge eating.

International registered report identifier (irrid): RR1-10.2196/66554.

Keywords: Research Domain Criteria; behavior; binge eating; glucagon-like peptide 1; insulin; leptin; longitudinal; reward; satiation; weight suppression.

Figure 1

Study protocol for participants enrolled before (left) and after (right) the onset of the COVID-19 pandemic. GLP-1: glucagon-like peptide 1; PR: progressive ratio.

Figure 2

Participant flow through the study for participants recruited before the onset of the COVID-19 pandemic. At the 6-month follow-up, 2 additional participants with BN-S completed questionnaire assessments but did not complete interviews for study visit 1. Participants who completed all visits at baseline were recruited to participate at the 12-month follow-up, whether or not they had completed 6-month follow-up. BN-S: bulimia nervosa and related syndromes.

Figure 3

Participant flow through the study for participants recruited after the onset of the COVID-19 pandemic. BN-S: bulimia nervosa and related syndromes.