Modest changes to glycemic regulation are sufficient to maintain glucose fluxes in healthy young men following overfeeding with a habitual macronutrient composition

Currently, it is unclear whether short-term overfeeding in healthy people significantly affects postprandial glucose regulation, as most human overfeeding studies have utilized induced experimental conditions such as the euglycemic-hyperinsulinemic clamp technique to assess glucoregulation. The aim of this study was to quantify glucose fluxes (rates of meal glucose appearance (Ra), disposal (Rd) and endogenous glucose production (EGP)) in response to 5 and 28 days of overfeeding (+45% energy) while maintaining the habitual diet's macronutrient composition (31.0 ± 1.9 % fat; 48.6 ± 2.2 % carbohydrate; 16.7 ± 1.4 % protein). To achieve this, meal tolerance testing was combined with the triple-stable isotope glucose tracer approach. Visceral adipose volume increased by ~15% with 5 days of overfeeding while there was no further change at 28 days. In contrast, body mass (+1.6kg) and fat mass (+1.3kg) were only significantly increased after 28 days of overfeeding. Fasting EGP, Rd and insulin were increased at 5, but unchanged after 28 days. Postprandial glucose and insulin responses were unaltered by 5 days of overfeeding, but were modestly increased after 28 days (P<0.05), while both meal Ra and glucose Rd were significantly increased after both 5 and 28 days (P<0.05). Despite this, overfeeding did not lead to alterations to postprandial EGP suppression. Thus, in contrast to findings from euglycemic-hyperinsulinemic clamp studies, chronic overfeeding did not affect the ability to suppress EGP or stimulate Rd under postprandial conditions. Rather, glucose flux was appropriately maintained following 28 days of overfeeding through modest increases in postprandial glycemia and insulinemia.