Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are increasingly prevalent metabolic disorders worldwide, with a complex bidirectional relationship between them. Currently, there is a lack of research on the trajectories of blood glucose and insulin concentration over time after eating in patients with MASLD and T2DM.</p> Methods <p>This clinical cohort included diagnosed T2DM patients in a large hospital over the past five years, was divided into an observation group (with MASLD) and a control group (without MASLD). The postprandial time trends of blood glucose and insulin concentration were analysed within two hours after eating. A strategy of backward iterative feature elimination combined with propensity score matching (PSM) was employed to screen for potential associated factors that might influence these trends.</p> Results <p>In total, there were 521 in the observation group and 373 in the control group. In terms of blood glucose, the postprandial time-concentration trajectories for both groups shown a significant time main effect (<i>F</i> = 1145.567, <i>P</i> &lt; 0.001), a significant group main effect (<i>F</i> = 15.340, <i>P</i> &lt; 0.001), and a significant time*group interaction effect (<i>F</i> = 2.873, <i>P</i> = 0.035); After matching all the factors, the time*group interaction effect of blood glucose was not significant, but the differences from group main effect still existed. In terms of insulin, the postprandial time-concentration trajectories for both groups shown a significant time main effect (<i>F</i> = 309.429, <i>P</i> &lt; 0.001), a significant group main effect (<i>F</i> = 6.319, <i>P</i> &lt; 0.012), and a significant time*group interaction effect (<i>F</i> = 20.057, <i>P</i> &lt; 0.001), but the trajectories crossed; After matching 4 factors such as Smoking, Essential Hypertension (EH), Body Mass Index (BMI), Triglyceride (TG) and Ca²⁺, neither the group main effect nor the time*group interaction effect on insulin was significant any more.</p> Conclusion <p>The postprandial trends of blood glucose and insulin concentration over time shown significant differences between T2DM patients with and without MASLD. IL-6 might be associated with the insulin resistance, while EH and Ca²⁺ might be related to the islet β-cell function. Smoking and TG might participate in both of the above processes. The strategy of backward iterative with PSM had demonstrated a relatively satisfactory effect in feature screening.</p>