Modulation of Amino Acid Metabolic Signatures by Supplemented Isoenergetic Diets Differing in Protein and Cereal Fiber Content

Context: Amino-acid (AA) metabolic signatures differ in insulin-resistant (IR) obese vs normal-weight subjects, improve after weight loss, and seem to predict the risk of type 2 diabetes. It is unknown whether weight-maintaining dietary measures aimed at influencing IR alter AA signatures of high-risk subjects. Setting and Design: In the randomized controlled Protein, Fiber and Metabolic Syndrome (ProFi-Met) trial we investigated effects of four isoenergetic, moderately fat-reduced diets varying in protein and cereal-fiber contents on complete AA metabolic signatures in 76 group-matched overweight or obese high-risk subjects. We analyzed the relation of whole-body and hepatic IR with AA signatures, body fat composition and liver fat, after 0, 6, and 18 weeks of dietary intervention. Discrimination between diets was further enhanced by providing tailored dietary supplements for twice-daily consumption over 18 weeks in all groups. Results: Baseline AA, including branched-chain signatures significantly related to IR, liver fat, and visceral fat mass. Isoenergetic variation of protein and cereal-fiber dietary contents, but not fat restriction, significantly influenced IR, whereas the relation of AA with IR changed with all diets. The tryptophan ratio was significantly suppressed in obese vs overweight participants, but increased after 6 weeks of high cereal-fiber intake to a nonobese phenotype. Modeling analyses revealed diet-induced alterations of complex AA profiles to relate to 70% and 62% of changes in whole-body and hepatic IR. Conclusions: We demonstrate that relatively short-term isoenergetic changes in the diet significantly alter the relation of AA signatures with IR, with possible implications on the determination and treatment of diabetes risk.