The association between glucose dynamics and energy intake in young, healthy women.

BACKGROUND: Glucose has been implicated in the control of appetite and food intake. This study investigated whether glycaemic patterns relate to energy intake and whether appetite-related hormones mediate this relationship.

METHODS: Thirty healthy young women (age: 25 ± 4 years; BMI: 21.4 ± 2.0 kg/m2) arrived at the laboratory at 8:00 AM after an overnight fast. Upon arrival, participants completed a 30 min resting period, during which the cannula was inserted, and all fasted glucose measurements were collected. Glucose was measured every 5 min using FreeStyle Libre 2™ continuous glucose monitors (CGM), and one venous plasma glucose (VPG) sample was obtained immediately after cannula insertion. Following the 30 min fasting measurement period, participants consumed a fixed breakfast and then remained in the laboratory for an additional 240 min. Glucose was monitored via CGM every 5 min and VPG was measured every 15 min after breakfast. Energy intake was assessed at 240 min using an ad-libitum homogeneous pasta meal. Subjective appetite ratings were collected fasted and every 15 min after breakfast. Appetite-related hormones, including insulin, acylated ghrelin (AG), total glucagon-like peptide-1 (GLP-1) and oxyntomodulin (OXM) were measured in the fasted state, immediately after breakfast (t = 0 min), and subsequently at 30 min intervals after breakfast until t = 240 mins. Menstrual cycle phase was recorded and included as a covariate in all analyses. Associations between glycaemic variables and satiety or energy intake were examined using generalised linear models with a gamma distribution and log link function, adjusting for BMI and menstrual cycle phase. Bootstrap-based causal mediation analyses were conducted to evaluate whether appetite-related hormones mediated any significant associations between glycaemic responses and satiety or energy intake.

RESULTS: CGM-derived glucose nadir (lowest concentration) and dip (deviation of nadir from baseline as a percentage) were significantly associated with subsequent energy intake. A higher glucose nadir was associated with lower energy intake (β = -0.17, p = 0.003), whereas a greater glucose dip was associated with higher energy intake (β = 0.007; p < 0.001). When standardised, a one standard deviation (SD) increases in glucose nadir corresponded to an approximately 13% reduction in energy intake, while a one-SD increase in glucose dip corresponded to an approximately 16% increase in energy intake. Glucose nadir (CGM: β = 0.23, p = 0.041; VPG: β = 0.26, p = 0.008) and dip (CGM: β = -0.01, p = 0.006; VPG: β = -0.012, p < 0.001) derived from both CGM and VPG were also significantly associated with overall satiety measured immediately before the ad libitum lunch. A one-SD increase in glucose nadir was associated with higher satiety (CGM: 20% increase; VPG: 20% increase), whereas a one-SD increase in glucose dip was associated with lower satiety (CGM: 15% reduction; VPG: 17% reduction). Causal mediation analyses provided no evidence that insulin, acylated ghrelin, total GLP-1, or oxyntomodulin mediated these associations (p ≥ 0.09).

CONCLUSIONS: Glucose dynamics including nadir and dip may influence satiety and subsequent energy intake. These data support for a role of glucose in models of appetite regulation.