Glucagon-like peptide-1, fibroblast growth factor 21, and other endocrine responses to alcohol ingestion in women before and after metabolic surgery.

INDRODUCTION: Glucagon-like peptide-1 (GLP-1) is integral to glucose homeostasis, appetite, and reward pathways in the brain, making GLP-1 receptor agonists effective treatments for type 2 diabetes, obesity, and potentially alcohol use disorder (AUD). Although metabolic surgery increases endogenous GLP-1, it is paradoxically associated with a higher risk of AUD. METHODS: Building on cross-sectional research indicating that alcohol consumption decreases endogenous GLP-1 and may contribute to a heightened risk of hypoglycemia post-metabolic surgery, this longitudinal, within-subject study examined whether acute alcohol intake reduced GLP-1 and increased fibroblast growth factor 21 (FGF21)-a liver-derived hormone implicated in glucose regulation and alcohol consumption in animal models -more profoundly after surgery. Seven women were assessed using a randomized, crossover design; they consumed after overnight fast a standardized alcohol-containing beverage or placebo during two separate visits before surgery and repeated these interventions ∼5 months post-surgery. Blood samples were collected over 3 hours to measure blood alcohol concentration (BAC), and plasma glucose, GLP-1, FGF21, insulin, and C-peptide. RESULTS: Post-surgery, BAC peaked faster and at higher concentrations, and alcohol clearance decreased by ∼28%-likely reflecting the loss of fat-free mass. However, the acute GLP-1 decrease and profound FGF21 increase following alcohol intake were not magnified in the postoperative period, nor did alcohol-induced reductions in glucose become more pronounced. DISCUSSION: These findings suggest that, despite substantial weight loss and improvements in insulin sensitivity, acute alcohol consumption in the fasted state elicits comparable effects on GLP-1, FGF21, and glycemia before and a few months after metabolic surgery. Further studies with larger and more diverse cohorts are warranted to confirm these observations, clarify long-term effects on alcohol metabolism and glycemic control, and inform strategies to mitigate the potential risk of AUD in this population. TRIAL REGISTRATION: NCT02766322.