Insulin Resistance Modifies the Glycemic Impact of Carbohydrate Across Distinct Meal Contexts: A Repeated-Measures Dual-CGM Study

Background/Objectives: Postprandial glycemic responses vary markedly among individuals, but it remains unclear whether the glycemic effect of incremental carbohydrate exposure is systematically modified by insulin resistance. We examined whether insulin resistance alters the carbohydrate–postprandial glucose dose-response across distinct meal contexts. Methods: We performed a secondary repeated-measures analysis of the publicly available CGMacros cohort. Forty-five adults spanning normoglycemia, prediabetes, and type 2 diabetes wore blinded FreeStyle Libre Pro and Dexcom G6 Pro continuous glucose monitors while recording meals for approximately 10 days. The primary outcome was 2-h incremental area under the glucose curve (iAUC). Mixed-effects models tested carbohydrate × HOMA-IR interactions, adjusted for protein, fat, fiber, premeal glucose, age, sex, and BMI. Breakfast was the primary structured context, lunch provided within-cohort contextual confirmation, dinner was a free-living contrast, and Dexcom analyses assessed cross-device robustness. Results: The primary Libre analysis included 423 breakfasts and 414 lunches from 44 participants. Higher HOMA-IR significantly amplified the iAUC associated with each 10-g increment in carbohydrate during breakfast (interaction β = 178.5 mg·min/dL per 1-SD higher HOMA-IR; 95% CI 79.5–277.5; p < 0.001) and lunch (β = 109.8; 95% CI 34.2–185.3; p = 0.004). The direction was supported with Dexcom during breakfast (β = 165.3; 95% CI 45.0–285.6; p = 0.007) and lunch (β = 87.9; 95% CI 2.6–173.1; p = 0.043) and remained robust in GEE, participant fixed-effects, random-slope, activity-adjusted, and other sensitivity analyses. No positive interaction was observed during dinner. Conclusions: In this observational secondary analysis, insulin resistance modified the glycemic impact of carbohydrate across two structured meal contexts, with supportive cross-device evidence. These findings are hypothesis-generating and do not establish HOMA-IR-based dietary prescriptions; prospective external validation is required.