Plasma Amino Acid Responses to an Oral Glucose Challenge Relate More Strongly to Body Adiposity Than to Insulin Resistance

The coexistence of obesity and insulin resistance is associated with elevated plasma amino acid concentrations. However, it remains unclear whether adiposity or insulin resistance is the stronger determinant of plasma amino acid dysregulation in this setting. Twenty-two adults (10 women, 12 men) spanning a broad range of body mass index (BMI) and insulin resistance underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast. Plasma glucose, insulin, and amino acid concentrations were measured serially, and insulin resistance/sensitivity was estimated from OGTT-derived glucose and insulin responses, using the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (Matsuda-ISI). Principal component analysis (PCA) of fasting plasma amino acid concentrations showed no clear separation by obesity or insulin resistance classifications. In contrast, PCA of OGTT-stimulated plasma amino acid concentrations revealed clearer clustering by BMI, fat mass, and waist circumference, whereas separation by HOMA-IR and Matsuda-ISI was less distinct. Importantly, regression analyses showed that BMI, fat mass, and waist circumference were significant predictors of OGTT-stimulated, but not fasting, amino acid responses, with waist circumference accounting for the greatest proportion of the variance in branched-chain amino acid responses during the OGTT (R2 = 0.54). In conclusion, measures of adiposity, particularly total fat mass and waist circumference, accounted for a greater proportion of the variance in plasma amino acid responses under physiologically stimulated conditions than indices of insulin resistance. These findings support the view that plasma amino acid concentrations reflect adiposity-related metabolic alterations more strongly than insulin resistance.