Timing of Meals and Sleep in the Mediterranean Population: The Effect of Taste, Genetics, Environmental Determinants, and Interactions on Obesity Phenotypes.

Circadian rhythms regulate the sleep-wake and feeding-fasting cycles. Sleep and feeding constitute a complex cycle that is determined by several factors. Despite the importance of sleep duration and mealtimes for many obesity phenotypes, most studies on dietary patterns have not investigated the contribution of these variables to the phenotypes analyzed. Likewise, they have not investigated the factors related to sleep or mealtimes. Thus, our aims were to investigate the link between taste perception and eating/sleep patterns and to analyze the effect of the interactions between sleep/meal patterns and genetic factors on obesity phenotypes. We conducted a cross-sectional analysis on 412 adults from the Mediterranean population. We measured taste perception (bitter, sweet, salty, sour, and umami) and assessed sleep duration and waketime. The midpoint of sleep and social jetlag was computed. From the self-reported timing of meals, we estimated the eating window, eating midpoint, and eating jetlag. Adherence to the Mediterranean diet was measured with a validated score. Selected polymorphisms in the TAS2R38, CLOCK, and FTO genes were determined, and their associations and interactions with relevant phenotypes were analyzed. We found various associations between temporal eating, sleep patterns, and taste perception. A higher bitter taste perception was associated with an earlier eating midpoint (p = 0.001), breakfast time (p = 0.043), dinner time (p = 0.009), waketime (p < 0.001), and midpoint of sleep (p = 0.009). Similar results were observed for the bitter taste polymorphism TAS2R38-rs713598, a genetic instrumental variable for bitter perception, increasing the causality of the associations. Moreover, significant gene-sleep interactions were detected between the midpoint of sleep and the TAS2R38-rs713598 (p = 0.032), FTO-rs9939609 (p = 0.037), and CLOCK-rs4580704 (p = 0.004) polymorphisms which played a role in determining obesity phenotypes. In conclusion, our study provided more information on the sleep and mealtime patterns of the general Spanish Mediterranean population than on their main relationships. Moreover, we were able to show significant associations between taste perception, specifically bitter taste; sleep time; and mealtimes as well as an interaction between sleep time and several genetic variants linked to obesity phenotypes. However, additional research is needed to better characterize the causality and mechanisms behind these associations.

Consistente asociación del polimorfismo rs7903146 en el gen TCF7L2 con mayor riesgo de diabetes en población mediterránea española / Consistent association of the rs7903146 polymorphism in the TCF7L2 gene with a higher risk of diabetes in a Spanish Mediterranean population

Introducción La diabetes tipo 2 (DT2) puede inducir la expresión de moléculas de adhesión celular (ICAM, VCAM) y citocinas (IL-6 y PCR). Posiblemente asociado con dichos mecanismos, el gen transcription factor 7-like 2 (TCF7L2) ha sido asociado con DT2 en diferentes poblaciones, aunque existen pocos datos en población mediterránea. Nuestro objetivo es estudiar la asociación de dicho gen con la DT2 y marcadores de inflamación en población de alto riesgo cardiovascular. Métodos Se incluyeron 1.001 participantes de alto riesgo cardiovascular del estudio PREDIMED-Valencia. Se determinó la glucemia en ayunas y las concentraciones de lípidos plasmáticos. En una submuestra aleatoria se determinaron las concentraciones de IL-6, PCR, VCAM e ICAM. Se analizó el polimorfismo rs7903146 (C>T) en el gen TCF7L2. Resultados La prevalencia de DT2 fue de 47,4%. La frecuencia de genotipos fue: 38,1% CC, 47,7% CT y 14,3% TT, siendo la frecuencia alélica del alelo T 0,381. Se hallaron diferencias significativas de concentraciones plasmáticas de glucosa según el genotipo (CC: 117,3±37,8; CT: 124,1±41,1; TT: 128,7±45,2mg/dl; p=0,011). Los portadores del alelo T presentan un mayor riesgo de DT2 (OR=1,37; 95%IC: 1,05-1,80; p=0,022) con respecto a individuos CC. El alelo T también se asoció como mayores concentraciones de VCAM (CC: 914,3±355,4; CT: 1.147,0±422,6; TT: 1.258,1±447,3 ng/ml; p=0,001). No se encontraron diferencias estadísticamente significativas para los demás marcadores de inflamación. Conclusión El alelo T del polimorfismo rs7903146 en el gen TCF7L2 se asocia con un mayor riesgo de DT2 en población mediterránea española, siendo consistente con los resultados obtenidos en otras poblaciones europeas (AU)

Introduction: Type 2 diabetes (T2D) can induce the expression of cell adhesion molecules (ICAM,VCAM) and cytokines (IL-6 and CRP). Possibly related to these mechanisms, the transcription factor 7-like 2 (TCF7L2) gene has been associated with T2D in distinct populations, but there are few data for the Mediterranean population. Our objective was to study the association of this gene with T2D and inflammation markers in a population at high cardiovascular risk. Methods: We included 1,001 high cardiovascular risk participants in the PREDIMED-Valencia study. Fasting blood glucose and plasma lipid concentrations were determined. Plasma concentrations of IL-6, CRP, VCAM and ICAM were also determined in a random subsample. Thers7903146 (C > T) polymorphism in the TCF7L2 gene was analyzed. Results: The prevalence of T2D was 47.4%. The frequency of genotypes was 38.1% for CC,47.7% for CT and 14.3% for TT (the allelic frequency of the T allele was 0.381). We found statistically significant differences in fasting plasma glucose concentrations depending on theTCF7L2 genotype (CC: 117.3±37.8; CT: 124.1±41.1; TT: 128.7±45.2 mg/dl; p = 0.011). Tallele carriers had an increased risk of T2D (OR = 1.37; 95% CI: 1.05-1.80; p = 0.022) compared with CC individuals. The T allele was also associated with higher concentrations of VCAM(CC: 914.3±355.4; CT: 1147.0±422.6; TT: 1258.1±447.3 ng/ml; p = 0.001). No statistically significant differences were found for the other markers of inflammation. Conclusion: Consistent with the results obtained in other European populations, this study found that the T allele of the rs7903146 polymorphism in the TCF7L2 gene is associated with an increased risk of T2D in a Mediterranean Spanish population (AU)