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

Am J Physiol Endocrinol Metab. 2019 Jun 1;316(6):E1061-E1070. doi: 10.1152/ajpendo.00500.2018. Epub 2019 Apr 9.


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 habitual macronutrient composition (31.0 ± 1.9% fat, 48.6 ± 2.2% carbohydrate, 16.7 ± 1.4% protein) in healthy, lean young men. 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 (+1.6 kg) and fat mass (+1.3 kg) were significantly increased only 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). However, meal Ra and glucose Rd were significantly increased after both 5 and 28 days of overfeeding (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.

Keywords: endogenous glucose production; glucose disposal; glucose tracer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism*
  • Energy Intake*
  • Fasting / metabolism*
  • Gluconeogenesis
  • Glucose / metabolism
  • Healthy Volunteers
  • Humans
  • Hyperphagia / metabolism*
  • Insulin / metabolism*
  • Intra-Abdominal Fat
  • Male
  • Postprandial Period*
  • Young Adult


  • Blood Glucose
  • Insulin
  • Glucose