Plausible Obesity-Related Chronometabolic and Nutrigenetic Nexus Concerning Dinner Glycemic Index and the FAAH C385A Variant

The interaction between chrono-nutrition (dinner intake), glycemic index (GI), and the <i>C358A</i> variant of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH), along with its impact on morning fasting insulin and glycemia, has not been previously explored. This study provides new insights into chronometabolic and nutrigenetic interactions. This study aims to analyze the association between the dinner GI and the C385A variant in the <i>FAAH</i> gene with respect to fasting glucose, insulin levels, and HOMA-IR in adults with obesity. It was hypothesized that the dinner GI, probably influenced by the <i>FAAH</i> variant, could be associated with glycemic homeostasis in adults with obesity. This is a secondary analysis of a cross-sectional study focused on 189 adults with obesity (129 women; mean age, 41 ± 12 years; mean BMI, 38.0 ± 5.2 kg/m²). Dietary intake was assessed through two 24 h food records, enabling the calculation of GI and macronutrient composition at each meal, especially dinner. Fasting-parameter setting and genotyping were done during the study. The lineal regression analyses were adjusted by age, sex, BMI, energy intake and dinner protein. Participants with lower fasting glucose levels had higher total GI and dinner GI values than those with higher fasting glucose levels, whereas no differences in dinner GI were observed across groups stratified by insulin or HOMA-IR levels. In fully adjusted regression models, dinner GI values remained inversely associated with fasting glucose levels (β = -0.172, 95%CI -0.298 to -0.045; <i>p</i> = 0.008). The <i>FAAH</i> C385A variant independently predicted lower insulin (β = -2.674, 95%CI -5.185 to -0.164; <i>p</i> = 0.037) and lower HOMA-IR (β = -0.731, 95%CI -1.364 to -0.099; <i>p</i> = 0.024) levels. No statistically significant interaction between dinner GI and the <i>FAAH</i> genotype was detected with respect to glycemia, insulin, and HOMA-IR. Overall, these findings indicate that the dinner GI influences fasting glucose levels in adults with obesity; the <i>FAAH</i> variant predicted lower insulin and HOMA-IR levels, supporting a plausible chrono-nutrigenetic interaction between carbohydrate quality, mealtime intake, and <i>FAAH</i> variation in metabolic regulation, which must be further studied.