Endogenous glucose production following sequential meals in humans: evidence for more prolonged suppression following ingestion of a second meal.

Single meal studies have shown that carbohydrate ingestion causes rapid and persistent suppression of endogenous glucose production (EGP). However, little is known about the regulation of EGP under real-life eating patterns where multiple carbohydrate-containing meals are consumed throughout the day. Therefore, we aimed to characterize the regulation of EGP in response to sequential meals, specifically during the breakfast-lunch transition. Nine healthy individuals (5 males, 4 females; 32 ± 2 years; 25.0 ± 1.4 kg/m2 ) ingested two identical mixed meals, each containing 25 g of glucose, separated by 4 h and EGP was determined using the variable infusion tracer-clamp approach. EGP was rapidly suppressed after both meals, with the pattern and magnitude of suppression being similar over the initial 75 min post-meal period. However, EGP suppression was more transient after breakfast compared to lunch, with EGP returning to basal rates 3 h after breakfast. In contrast, EGP remained in a suppressed state for the entire 4 h post-lunch period. This occurred despite each meal eliciting similar plasma glucose and insulin responses. However, there was greater suppression of plasma glucagon levels after lunch, likely contributing to this response. These findings highlight the potential for distinct regulation of EGP with each meal of the day and suggest that EGP may be in a suppressed state for much of the day, since EGP did not return to basal rates even after a lunch meal containing a modest amount of carbohydrate.