Heterogeneity in postprandial glucose-insulin and triacylglycerol dynamics and associations with plasma metabolome and body composition in obesity

We are only beginning to understand the extent and reasons for the individual variation in postprandial response dynamics in key hormones and metabolites such as insulin, glucose and triacylglycerols (TAGs). More nuanced statistical approaches for postprandial curve analyses, coupled with phenotyping of curve-associated factors, may help uncover the underlying physiology and possible associations with disease risk. In a clinical trial of 190 adults (90 males, 100 females) with abdominal obesity (age: 21-56 BMI: 26-54), we used functional principal component analysis (FPCA) to examine postprandial serum glucose, C-peptide, and TAGs after a 4-hour standardized mixed meal test. Correlations were explored between identified curve patterns and more than 100 anthropometric and fasting biochemistry traits. Postprandial curve levels, peaks, and dips varied substantially. While the primary patterns in postprandial glucose, C-peptide, and TAGs uncovered by FPCA corresponded with area under the curve (AUC), the presence and timing of curve peaks and dips was uncorrelated with AUC. Males had higher postprandial levels and larger variation than females. Over 40% of the participants had non-synchronized postprandial glucose and C-peptide curves. A postprandial phenotype characterized by elevated and delayed postprandial peaks in glucose and C-peptide, and a high postprandial TAG level and peak, was strongly associated with multiple blood biomarkers and anthropometric traits linked to insulin resistance and liver pathologies (correlation range: -0.49, 0.63). While our findings support the general usefulness of postprandial AUC, FPCA provided detailed insight into individual postprandial glucose and insulin dynamics which may inform improved diagnostics and personalized dietary advice.