Individual glycemic responses scale predictably with the glycemic index: evidence against person-specific food effects

BACKGROUND: Recent personalized nutrition research has reported large inter-individual differences in postprandial glucose responses to identical foods, raising questions about whether these differences reflect food-specific personal effects or normal day-to-day variability in glucose tolerance. OBJECTIVES: To quantify the relative contributions of measurement variability vs person-specific effects to inter-individual glycemic variation, and to define substitution thresholds for when glycemic index (GI) differences produce distinct physiological effects. METHODS: In this secondary analysis with simulated validation, data from 382 healthy adults (1,022 glucose reference tests, 1,116 food tests across 9 carbohydrate-rich foods) were analyzed using a direct comparison scaling model, in which an individual's food response equals their glucose reference response scaled by the food's average GI. Sensitivity analyses included single-reference predictions, restriction to participants with ≥3 reference tests, and exclusion of a protocol-deviating food. RESULTS: Predicted errors did not exceed the observed glucose reference test-retest variability (mean root mean square deviation [RMSD]: 0.78 vs. 1.02 mmol/L; Cohen's d = 0.54 [0.45, 0.63]), with ∼90% of predictions falling within each participant's own test-retest range. Bland-Altman analysis confirmed negligible systematic bias (-0.01 mmol/L). Synthetic datasets generated from glucose variability and average GI values reproduced observed response distributions without person-specific parameters. GI differences of ≥15 units produced reliably distinguishable responses in a given individual. All sensitivity analyses yielded equal or stronger effect sizes. CONCLUSIONS: In healthy adults under standardized conditions, inter-individual variation in glycemic responses is predominantly accounted for by variability in day-to-day glucose tolerance, propagating through the GI ratio. The GI concept performs within the reproducibility limits of input data.