Ghrelin tied to longitudinal weight gain in girls and young women with anorexia nervosa: JAMA

The study provides evidence supporting further investigations into the role of ghrelin biology in weight regulation in anorexia nervosa.

Anorexia nervosa (AN) is a debilitating chronic illness with a high rate of premature mortality, one of the highest among psychiatric diseases. The mainstay of treatment includes interventions to restore body weight, which is challenged by motivations driven by the illness to remain thin. Currently, no medications have been approved by the US FDA (Food and Drug Administration) for AN; modulating endocrine signals involved in energy homeostasis, such as ghrelin, is being investigated.

Ghrelin is a peptide hormone secreted primarily from the stomach that acts on the growth hormone secretagogue receptor 1a to promote weight gain and food intake in animal models. Even though intravenous ghrelin administration increases food intake in the short term, surprisingly, increases in endogenous ghrelin have not been linked with prospective weight gain in humans, except in infants born small for gestational age.

In anorexia nervosa, the administration of intravenous ghrelin increases food intake, and endogenous levels of ghrelin are significantly raised, related to increased secretory bursts. It is unknown whether such high circulating ghrelin levels have a role in long-term weight homeostasis. It is critical to understand this association because of an urgent need for novel therapeutics to assist with weight restoration in this population.

Against the above background, Youngjung R. Kim, Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues aimed to examine the association between baseline ghrelin and future weight change in people with anorexia nervosa in a prospective cohort study.

The study was conducted in the US between April 1, 2014, and March 31, 2020. Recruitment was done of women and girls aged 10 to 22 years from the greater Boston area, enrolled and followed up for 18 months. Statistical analyses were conducted between January and August 2022.

The study's primary outcomes were changes in age- and sex-standardized BMI (body mass index) percentiles from baseline to 9- and 18-month follow-up.

The study led to the following findings:

• The study included 68 girls and young women (16% Asian, 6% Hispanic or Latina, 75% White [non–Hispanic or Latina], and 3% other race or ethnicity), including 33 healthy controls of similar Tanner stage and 35 with anorexia nervosa.
• Anorexia nervosa and healthy control groups were not statistically different by Tanner stage, race and ethnicity, number of completing follow-up visits, and the duration between baseline and follow-up visits.
• At baseline, people with anorexia nervosa were slightly older (median, 20.1 vs 18.7 years), had lower body mass index percentiles (median 2.4 vs 52.9), and had increased circulating ghrelin area under the composite curve index (median, 1389.4 vs 958.5 pg/mL) compared with healthy people.
• In linear mixed-effects regression analyses, baseline ghrelin was linked with prospective weight gain after adjusting for diagnosis, race, age, and duration of follow-up (odds ratio, 2.35).

"In this cohort study, endogenous ghrelin was tied to longitudinal weight gain in people with anorexia nervosa," the researchers wrote. "Further studies are warranted to confirm this result and investigate its potential clinical utility in treatment development."

Reference:

Kim YR, Lauze MS, Slattery M, et al. Association Between Ghrelin and Body Weight Trajectory in Individuals With Anorexia Nervosa. JAMA Netw Open. 2023;6(3):e234625. doi:10.1001/jamanetworkopen.2023.4625