Endocrine responses to alcohol ingestion in women with and without metabolic surgery

Glucagon-like peptide-1 (GLP-1)-based therapies, widely used for treating obesity and type 2 diabetes, also show potential for reducing alcohol-seeking behavior. However, the effects of alcohol on endogenous GLP-1 and related peptides remain poorly understood, especially in individuals who have undergone metabolic surgery, a group at elevated risk for alcohol use disorder (AUD) despite an enhanced GLP-1 response post-surgery. This work integrates findings from cross-sectional and longitudinal placebo-controlled studies that examined the acute endocrine and glycemic effects of alcohol ingestion in women with and without a history of metabolic surgery. In the cross-sectional study, 18 post-surgical and 14 control women were assessed for hormonal and metabolic responses to an alcohol dose. Alcohol decreased GLP-1 by 34% in both groups and reduced ghrelin more in controls (27%) than in the surgery group (13%). Alcohol modestly lowered glucose and transiently increased insulin secretion in both groups. However, 28% of post-surgical women reached hypoglycemic levels, compared to none in the control group. In the longitudinal arm, seven women underwent identical alcohol/placebo challenges before and ~5 months after surgery. We observed that post-surgery, blood alcohol concentrations (BAC) peaked faster and higher, with ~28% lower alcohol clearance, likely reflecting the loss of fat-free mass. However, the acute decrease of GLP-1 and marked increase of fibroblast growth factor 21 (FGF21) following alcohol intake did not significantly differ before and after surgery. Similarly, alcohol-induced glucose reductions were not more pronounced postoperatively. Together, these findings confirm that acute alcohol consumption reduces endogenous GLP-1 and increases hypoglycemia risk after metabolic surgery. They also suggest that, despite substantial weight loss and improvements in insulin sensitivity post-surgery, acute endocrine responses to alcohol in a fasted state remain largely comparable. These insights support the relevance of gut–brain and liver–brain peptide systems in understanding alcohol's effects and AUD risk in surgical populations.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Molina Castro, Mariel

Contributors dc:contributor

• Pepino, Marta Y.
• Miller, Michael
• Amengual, Jaume

• Alcohol Use Disorder
• Weight-loss Surgery
• Glucose Metabolism

Statement dc:rights

• Copyright 2025 Mariel Molina Castro

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129981

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129981