Test of a biobehavioral model linking weight suppression to binge-eating severity via leptin and glucagon-like peptide 1 in bulimia nervosa and related syndromes in women

Abstract

Background: Weight suppression represents the difference between highest and current body weight and predicts maintenance of bulimia nervosa and related syndromes (BN-S). This study tested a biobehavioral model of binge-eating severity in which greater weight suppression links to reduced leptin, which links to reduced glucagon-like peptide 1 (GLP-1) release, which links to both decreased reward satiation and increased reward valuation, which link, respectively, to excessive food intake and loss of control while eating - the defining features of DSM-5 binge-eating episodes.

Methods: Women (N = 399) who met DSM-5 criteria for bulimia nervosa or another eating disorder with binge eating (n = 321) or had no lifetime eating disorder symptoms (n = 78) participated in a multi-visit protocol, including structured clinical interviews, height, weight, weight history, percent body fat, fasting leptin, post-prandial GLP-1 response to a fixed meal, and self-report and behavioral assessments of food reward satiation (ad lib meal) and food and nonfood reward valuation (progressive ratio tasks).

Results: A structural equation model (SEM) demonstrated excellent fit to data with significant pathways from greater weight suppression to lower leptin, to blunted GLP-1 response, to lower reward satiation, to larger eating/binge-eating episode size, with significant indirect paths through leptin, GLP-1, and reward satiation. SEM with paths via reward valuation to loss of control eating demonstrated inadequate fit.

Conclusions: Findings specifically link reduced GLP-1 response to severity of binge-episode size and support weight history assessment in eating disorders, DSM-5 over ICD-11 criteria for binge eating, and may inform future clinical trials of GLP-1 agonists for BN-S.

Keywords: GLP-1; binge eating; bulimia nervosa; eating disorders; glucagon-like peptide 1; leptin; reward; satiation; weight suppression.

Figure 1.

Abbreviations: GLP-1 = glucagon-like peptide 1.

Figure 2.

Abbreviations: GLP-1 = glucagon-like peptide 1; RV = reward valuation; RV-E = reward valuation-effort Note: Circles represent latent variables and squares represent observed variables. The latent variable for satiation (self-report) consisted of three indicators: Area under the curve visual analog ratings for fullness, satiation, and hunger (reversed scored) during the fixed meal. Lower satiation (behavior) is represented by greater food intake during the ad lib meal. The latent variable for reward valuation-effort (behavior) consisted of three indicators: progressive ratio food task breakpoint; progressive ratio game task [fasted state] breakpoint; progressive ratio game task [fed state] breakpoint. The latent variable for reward valuation (self-report) included three indicators: visual analog scale ratings for how much participants ‘want’ the reward for which they were about to work administered just prior to each progressive ratio task. Weight suppression was calculated as percent of body mass index (BMI) loss from highest adult BMI and current BMI. Leptin represents standardized residuals of average fasting leptin values across two separate days, controlling for assay in which samples were run. GLP1-response represents standardized residuals for GLP1-total response, controlling for assay in which samples were run.

Figure 3.

Abbreviation: BN-S = bulimia nervosa and related syndromes. Note: Study Visit 3 was dropped from the protocol for participants enrolled after onset of the COVID-19 pandemic. Participants with Study Visit 3 data include 255 of 301 (85%) enrolled before pandemic onset, including 212 of 256 (84%) with BN-S and 43 of 45 (96%) Control participants. The number who actively dropped out is included in the total number of individuals who did not return. We estimate that n = 13 participants were unable to complete visits due to the COVID-19 pandemic.