Gluco-metabolic effects of oral and intravenous alcohol administration in men

Abstract

Background: Ingestion of the calorically dense compound alcohol may cause metabolic disturbances including hypoglycaemia, hepatic steatosis and insulin resistance, but the underlying mechanisms are uncertain. The gastrointestinal tract is well recognised as a major influencer on glucose, protein and lipid metabolism, but its role in alcohol metabolism remains unclear.

Objective: To examine the effects of oral and intravenous alcohol, respectively, on plasma concentrations of several gluco-regulatory hormones including serum/plasma insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF21).

Design and methods: In a double-blinded, randomised, crossover design, we subjected 12 healthy men to intragastric ethanol infusion (IGEI) and an isoethanolaemic intravenous ethanol infusion (IVEI) (0.7 g alcohol per kg body weight), respectively, on two separate experimental days.

Results: Isoethanolaemia during the two alcohol administration forms was obtained (P = 0.38). During both interventions, plasma glucose peaked after ~30 min and thereafter fell below baseline concentrations. GIP and GLP-1 concentrations were unaffected by the two interventions. Insulin concentrations were unaffected by IGEI but decreased during IVEI. C-peptide, insulin secretion rate and glucagon concentrations were lowered similarly during IGEI and IVEI. FGF21 concentrations increased dramatically (nine-fold) and similarly during IGEI and IVEI.

Conclusions: Alcohol does not seem to affect the secretion of incretin hormones but decreased insulin and glucagon secretion independently of gut-derived factors. IGEI as well as IVEI potently stimulate FGF21 secretion indicating a gut-independent effect of alcohol on FGF21 secretion in humans.

Keywords: FGF21; alcohol; glucagon; glucose; incretin hormones; insulin.

Figure 1

Plasma ethanol concentrations (A) and corresponding area under the curve (AUC) values (B) and plasma glucose concentrations (C) and corresponding AUCs (D) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Data are mean ± s.e.m.

Figure 2

Serum insulin concentrations (A) and corresponding area under the curve (AUC) values (B) and serum C-peptide concentrations (C) and corresponding AUCs (D) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Asterisks indicate statistically significant interactions between intervention and time evaluated by multiple comparisons. *P < 0.05; **P < 0.005. Data are mean ± s.e.m.

Figure 3

Insulin secretion rate (ISR) (A) and corresponding area under the curve (AUC) values (B) and insulin/glucose ratio (C) and corresponding AUCs (D) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Data are mean ± s.e.m.

Figure 4

Plasma glucagon concentrations (A) and corresponding area under the curve (AUC) values (B) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Data are mean ± s.e.m.

Figure 5

Plasma glucose-dependent insulinotropic polypeptide (GIP) concentrations (A) and corresponding area under the curve (AUC) values (B), and plasma glucagon-like peptide 1 (GLP-1) concentrations (C) and corresponding AUCs (D) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Asterisks indicate statistically significant interactions between intervention and time were evaluated by multiple comparisons. **P < 0.005; ***P < 0.0005. Data are mean ± s.e.m.

Figure 6

Plasma fibroblast growth factor 21 (FGF21) concentrations (A) and corresponding area under the curve (AUC) values (B) during intragastric alcohol infusion (IGEI) (black circles) and intravenous alcohol infusion (IVEI) (white circles). Data are mean ± s.e.m.