High animal protein and high plant protein meals differentially alter postprandial plasma amino acid concentrations but not glucose homeostasis in people with overweight/obesity in a randomized, cross-over, single-meal study.

BACKGROUND: In population studies, high protein, particularly high animal protein, intake is associated with an increased risk of developing type 2 diabetes. Results from preclinical studies suggest this association might be mediated by branched-chain and other essential amino acids. OBJECTIVE: Interrogate putative mechanisms linking high protein intake and diabetes risk. METHODS: We conducted a randomized, cross-over, single-meal study in people with overweight/obesity to compare the effects of a standard meal (∼18 g protein/15% meal energy) and high protein meals (∼28 g protein/22% meal energy) enriched with protein from either animal (n=21) or plant (n=21) sources on postprandial plasma amino acid, glucose, and key glucoregulatory hormone concentrations (180-min area-under-the-curve). RESULTS: Postprandial plasma amino acids were higher after the high-protein meals than the standard (STD) meal, with greater increases (all p<0.05) after the high animal protein (HAP) than the high plant protein (HPP) meal in total essential (HAP vs STD, 28±3%; HPP vs STD, 19±3%; mean±SEM) and total branched-chain (HAP vs STD, 36±3%; HPP vs STD, 24±3%), but not total (all) amino acids. Compared with the STD meal, both the HAP and HPP meals resulted in lower plasma glucose (HAP vs STD, -4.3±2.1%; HPP vs STD, -5.2±1.5%) and higher glucagon (HAP vs STD, 48±12%; HPP vs STD, 44±13%), glucagon-like peptide 1 (HAP vs STD, 23±6%; HPP vs STD, 30±12%), and insulin in relationship to glucose, without differences between the HAP and HPP meals. CONCLUSIONS: Both the amount and type of protein are determinants of postprandial plasma amino acid concentrations, but only the amount, not the type of protein is a determinant of plasma glucoregulatory hormone and glucose concentrations. Therefore, essential and branched-chain amino acids are not important regulators of postprandial glucose homeostasis. Non-protein dietary or non-dietary factors likely mediate differential effects of high animal and high plant protein intake on glucose metabolism. CLINICALTRIALS: gov, numbers: NCT03994367 and NCT05235464.