Glycomacropeptide Impacts Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, and the Fecal Microbiome in Obese Postmenopausal Women

Abstract

Background: Obesity with metabolic syndrome is highly prevalent and shortens lifespan.

Objectives: In a dose-finding crossover study, we evaluated the effect of glycomacropeptide (GMP) on satiety, glucose homeostasis, amino acid concentrations, inflammation, and the fecal microbiome in 13 obese women.

Methods: Eligible women were ≤10 yr past menopause with a body mass index [BMI (in kg/m²)] of 28 to 35 and no underlying inflammatory condition affecting study outcomes. Participants consumed GMP supplements (15 g GMP + 10 g whey protein) twice daily for 1 wk and thrice daily for 1 wk, with a washout period between the 2 wk. Women completed a meal tolerance test (MTT) on day 1 (soy MTT) and day 7 (GMP MTT) of each week. During each test, subjects underwent measures of glucose homeostasis, satiety, cytokines, and the fecal microbiome compared with that of usual diet, and rated the acceptability of consuming GMP supplements.

Results: The mean ± SE age of the 13 women was 57 ± 1 yr, with a median of 8 yr (range: 3-9 yr) past menopause and a BMI of 30 (IQR: 29-32). GMP was highly acceptable to participants, permitting high adherence. Metabolic effects were similar for twice or thrice daily GMP supplementation. Glucose, insulin, and cytokine concentrations were no different. The postprandial area under the curve (AUC) for glucagon concentrations was significantly lower, and the insulin-glucagon ratio was significantly higher with GMP than that with the soy MTT. Postprandial AUC amylin concentration was significantly higher with GMP than that with the soy MTT and correlated with C-peptide (P < 0.001; R² = 0.52) and greater satiety. Ingestion of GMP supplements twice daily reduced members of the genus Streptococcus (P = 0.009) and thrice daily consumption reduced overall α diversity.

Conclusions: GMP is shown to increase amylin concentrations, improve glucose homeostasis, and alter the fecal microbiome. GMP can be a helpful nutritional supplement in obese postmenopausal women at risk for metabolic syndrome. Further investigation is warranted. This trial was registered at clinicaltrials.gov as NCT05551091.

Keywords: Streptococcus; branched chain amino acids; glucagon; glucose tolerance; inflammation; obesity; satiety.