1469-P: Genetic Variation in a Bitter Taste Receptor Gene Associates with Random and Especially Postprandial Blood Glucose

Taste receptors canonically mediate taste perception and food preferences. However, the recent discovery of bitter taste receptors in the gut suggests novel functions in satiety signaling and glucose homeostasis. Given the strong genetic component to taste, we aimed to evaluate whether genetic variation in bitter taste receptor genes associates with glucose homeostasis. Among 62,181 UK Biobank participants of European genetic ancestry without diabetes and with complete genetic, diet and random glucose (RG) data, we derived common taste diplotypes conferring low (“nontaster”; 48.4%), average (“taster”; 26.3%), or high (“supertaster”; 25.3%) bitter perception from three variants in the TAS2R38 bitter taste receptor gene (rs713598, rs1726866, rs10246939; linkage disequilibrium r²>0.85). We used generalized linear models to assess their associations with RG at 0 to 12 hours (hrs) post ingestion, adjusting for demographic covariates, fasting time (hrs) and BMI (Base model), and subsequently for diet and lifestyle factors. In unadjusted analyses, RG differed significantly across taste diplotypes (P=0.03) while reported energy (kcal/d) and macronutrient (%kcal) intake and BMI were similar. In the Base model, supertasters had a small but significantly lower RG compared to nontasters (Beta=-0.014 mmol/L; 95% CI: -0.03, -0.003; P=0.015), which remained significant after further adjustment for diet and lifestyle factors (P=0.013). RG did not differ significantly between tasters and either diplotype. In sensitivity analyses stratified by fasting time, RG was 0.042 (95% CI: -0.07, -0.01; P=0.006) mmol/L lower for supertasters than nontasters in the ≤2 hr fasting window (akin to a postprandial state), but was not significantly different in later fasting windows. These data suggest taste receptors may function in glucose homeostasis independent of diet, and genetic variation in bitter taste receptor genes may particularly impact the postprandial state.