Abstract
High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia.
Highlights
High circulating concentrations of branched chain and aromatic amino acids (BCAAs and AAAs) are associated with several characteristics of diabetes, such as increased glycaemia and insulin resistance [1,2,3,4,5,6]
We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia
We have the possibility of examining the postprandial kinetics of DMAAs in healthy subjects, how it is affected by the dietary protein source originating from a meal, and how fasting and postprandial DMAAs relate to fasting levels of glucose, the core phenotype defining diabetes mellitus
Summary
High circulating concentrations of branched chain and aromatic amino acids (BCAAs and AAAs) are associated with several characteristics of diabetes, such as increased glycaemia and insulin resistance [1,2,3,4,5,6]. In particular a score of isoleucine (Ile), tyrosine (Tyr), and phenylalanine (Phe) has been a strong predictor [5, 7] Whether these diabetes associated amino acids (DMAA) are causally related to insulin resistance and diabetes or just biomarkers for the underlying processes is still under debate and several possible mechanisms for causality have been discussed [9, 10]. Several possible processes could contribute to increased circulating DMAAs, including protein dietary intake, altered DMAA uptake rate into tissue, breakdown of muscle proteins, and altered DMAA metabolism. Which of these processes, that predominantly causes the increase in fasting circulating DMAAs, has not yet been established? That predominantly causes the increase in fasting circulating DMAAs, has not yet been established? Assuming that the association between DMAAs and diabetes development is causal, it is instrumental to identify which of these principally different processes that explain the association, in order to establish whether changing the intake of DMAAs is meaningful for diabetes prevention
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