## 4 Discussion
Additionally, the effectiveness of the full-course meal manner observed in this study can be explained by the small portions and intervals of the meal taken during one hour of mealtime. Because the amount of nutrients in each bite when eating over a long period of time was smaller than that when eating fast, the concentration of early postprandial glucose and insulin was reduced, while GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) might have been induced intermittently in the one-hour mealtime, as we have reported in the paper [13; 32]. A key strength of this study lies in its design as the first randomized controlled crossover interventional trial to demonstrate the amelioration of the MAGE through the consumption of a meal in a full-course meal manner, over one hour. This eating pattern effectively replicates the traditional full-course meal approach, in which dishes are served sequentially over an extended period. The observed reductions in glycemic responses may be beneficial for individuals both with and without T2 DM, as higher MAGE levels have been associated with an increased risk of T2 DM, arteriosclerosis, cardiovascular diseases [33], and dementia [34], even before the onset of T2 DM [35]. Therefore, reducing MAGE may contribute to lowering the risk of developing impaired glucose tolerance, T2 DM, and cardiovascular diseases in the long term [36; 37; 38; 39]. Furthermore, the delayed consumption of the carbohydrate dish, which resulted in reduced early postprandial insulin secretion, may be particularly beneficial for East Asian populations, including Japanese individuals. This is because early-phase and total insulin secretion in East Asians is significantly lower than in Caucasians [40]. The suppression of excessive insulin may help to maintain the function of \(\beta\) cells in the pancreas, consequently helping to lower the risk of T2 DM [41]. Insulin modulates vascular function through its effects on vasoreactivity, lipid metabolism, and inflammation, and through these multiple pathways, insulin dysregulation could contribute to neurodegeneration [42]. Because insulin plays a critical role in proteostasis, it has been reported to influence the clearance of amyloid \(\beta\) peptides and the phosphorylation of tau, both of which are hallmarks of [PERSON]'s disease [42]. Additionally, hyperinsulinemia is a key etiological factor in the development of metabolic syndrome, type 2 diabetes mellitus (T2 DM), cardiovascular disease, and cancer [43]. One of the key characteristics of traditional Japanese cuisine (Washoku), recognized as an Intangible Cultural Heritage by UNESCO, is its emphasis on home-cooked mealsand the practice of spending extended periods enjoying food with others [44]. However, traditional dietary patterns have increasingly shifted toward Western-style eating habits, which prioritize fast food and ultra-processed products over the enjoyment and sharing of home-cooked meals. Modern lifestyles and globalization have further contributed to changes in eating behaviors, resulting in meals being consumed quickly and with diminished social interaction in many countries, including Japan. Meal satisfaction is not solely determined by portion size or caloric intake [45]; instead, the act of taking time to eat and sharing food and beverages with others are critical components. In contrast, consuming fast food in a short period of time, with limited social engagement, is often associated with reduced meal satisfaction [46; 47]. Our findings underscore the importance of not only the composition of macro- and micronutrients, but also different eating manners, in maintaining optimal metabolic responses. Occasionally taking the time to enjoy each dish individually, with friends and family, can be considered a factor that enriches life.