2129-LB: Genetic Predisposition for Macronutrient Preference Associates with Postprandial Glycemic Responses to Foods—A Recall-by-Genotype Study

by sugaradmin



Introduction and Objective: Identifying predictors of postprandial glycemic response variability is critical to advance precision medicine for metabolic diseases. We evaluated whether polygenic scores for macronutrient preference influence postprandial responses to mixed-meals in a clinical setting.Methods: We performed a recall-by-genotype study in 22 adults (21-65 yrs; 54% female) without obesity or metabolic disease, recruited based on high genetic predisposition to consume a high carbohydrate (HC; n=12) or high fat (HF; n=10) diet. We measured postprandial glycemic responses to a standardized and self-selected (high in carbohydrate or fat) mixed-meal, and used multivariable linear and mixed-effects models adjusted for age, sex, genetic PCs, BMI and baseline metabolite values to determine the effect of genetic susceptibility to macronutrient preference on postprandial glucose and insulin responses (120 min incremental AUC (iAUC) and metabolite levels at 0-180 min, respectively).Results: Age, sex and BMI were similar between genotypes. In standardized mixed-meal tests, the HC genotype was associated with lower glucose excursions than the HF genotype (120 min iAUC, Beta = -85.4 mmol/L; 95% CI = -139.0, -32.1; P = 0.008), despite lower insulin secretions, particularly at 60 min (P, genotype x time = 0.026). For self-selected meals, the effect of meal type on postprandial responses differed by genotype: for the HC genotype, a high fat (vs high carbohydrate) meal led to lower glucose excursions (120 min iAUC, Beta = -58.5 mmol/L; 95% CI = -105.2, -11.7; P = 0.035) while there were no significant effects of meal type for the HF genotype.Conclusion: Genetic susceptibility to prefer carbohydrate or fat was associated with postprandial glycemic responses, particularly to high-fat foods, in metabolically healthy adults, providing a basis to leverage genetics of dietary intake in precision medicine for metabolic disease prevention.

Disclosure

J.E. Gervis: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Consultant; Wolters Kluwer Health, Patient Square Capital. M. Udler: Research Support; Novo Nordisk. J. Merino: None.

Funding

American Diabetes Association (7-21-JDFM-005)



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