Whole-Grain Staple Replacement and Cardiometabolic Phenotypes in Adults at High Risk of Type 2 Diabetes: An Extended Randomized-Trial Analysis with NHANES and Country-Level Context

Background/Objectives: Adults at high risk of type 2 diabetes frequently show concurrent dyslipidemia, insulin resistance, and central adiposity before overt diabetes develops. We evaluated cardiometabolic responses to standardized whole-grain staple replacement and examined grain-quality patterns in free-living and country-level settings. Methods: This secondary exploratory analysis included 144 participants (48 per group) from a 12-week, three-arm randomized dietary trial. Participants were analyzed according to their randomized assignments to 100 g/day, 50 g/day, or control. Lipid, anthropometric, body composition, and composite cardiometabolic phenotypes were evaluated. Longitudinal and time-weighted cumulative effects were estimated using linear mixed-effects and regression models, with Benjamini–Hochberg false discovery rate (FDR) correction applied within the corresponding multiplicity domains. Complementary analyses included 30,769 NHANES adults without diabetes, including 12,169 with prediabetes, and descriptive country-level data on whole-grain intake, high-FPG-attributable diabetes burden, and cereal supply. Results: Within the extended phenotype panel, HWG versus control time-weighted cumulative effects included triglycerides (β = −0.220, 95% CI −0.397 to −0.043; FDR-adjusted p = 0.047), the atherogenic index of plasma (β = −0.125, −0.191 to −0.060; FDR-adjusted p = 0.002), and the triglyceride–glucose index (β = −0.301, −0.429 to −0.173; FDR-adjusted p < 0.001). Conventional lipid components showed distinct temporal responses. In NHANES, higher whole-grain exposure and more favorable grain-quality ratios were associated with lower adiposity- and insulin resistance-related phenotypes, whereas refined-grain exposure generally showed the opposite pattern. Country-level analyses showed marked heterogeneity in whole-grain intake, diabetes burden, and cereal supply context. Conclusions: Standardized whole-grain staple replacement was associated with short-term changes across several cardiometabolic dimensions in adults at high risk of type 2 diabetes, with the clearest extended-phenotype signals involving triglyceride-related and glucose–triglyceride coupling measures. NHANES identified cross-sectional grain-quality associations in free-living adults; country-level analyses described heterogeneity in whole-grain intake, diabetes burden, and cereal supply context.