Postprandial glycaemic dips predict appetite and energy intake in healthy individuals

Abstract

Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2-3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0-2 h and glucose incremental area under the blood glucose curve at 0-2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2-3 h relative to baseline level predicted an increase in hunger at 2-3 h (r = 0.16, P < 0.001), shorter time until next meal (r = -0.14, P < 0.001), greater energy intake at 3-4 h (r = 0.19, P < 0.001) and greater energy intake at 24 h (r = 0.27, P < 0.001). Results were directionally consistent in the US validation cohort. These data provide a quantitative assessment of the relevance of postprandial glycaemia in appetite and energy intake modulation.

Conflict of interest statement

Conflict of interest statement: TD Spector, SE Berry, AM Valdes, PW Franks, A Chan are consultants to Zoe Global Ltd (“Zoe”). J Wolf, G Hadjigeorgiou, H Al Khatib, P Wyatt and I Linenberg are or have been employees of Zoe. JE Blundell is a member of Zoe Global scientific Advisory Board. Other authors have no conflict of interest to declare.

Figures

Extended Data Figure 1

Extended Data Figure 2

Extended Data Figure 3

Figure 1. Average glycemicresponses to standardised breakfasts, illustrating key measures used in study

(n=1,070, m=8,624).Four phases were studied (see methods) namely: Phase 1: Pre-Meal: (up to 30 minutes before the standardised meal starts. Phase 2: Standardised Meal: (from 0 to +2 hours is the conventional time period for measuring glucose response) Phase 3: Post-Meal: The phase +2 hours to +3 hours after the meal. All participants were asked to fast up until 3 hours post-meal so no energy intake has taken place.Phase 4: Ad libitum meals: when participants were allowed to eat again. See methods for details

Figure 2. Postprandial measures by top and bottom quartiles of 2-3h Glucose Dip

(n=763, m=5667 (UK n=685, m=5667, US n=78, m=602). Participants were divided into quartiles of their average Glucose Dip2-3h, following consumption of’ OGTT, High Carb, UK average, High Fat, and High Fibre standardised breakfasts (n=5667). The participants with the largest dips (Q4) are compared to those with the smallest dips (Q1), according to their Change in Hunger2-3h, Change in Alertness2-3h, Time until the next meal, ad libitum Energy Intake3-4h immediately after the end of the fasting period, and ad libitum Energy Intake24h.Boxplots showing median, means (indicated by a + sign) interquartile ranges and 90% confidence intervals are shown. P-values from two sided t-tests are reported. Sample sizes for each panel (a) change in hunger and (b) change in alertness Q1(n=161) Q4(n=162) (c) time in minutes until next meal (d) energy intake between 3 and 4 hours after the meal (e) energy intake in the 24 hours after the meal Q1(n=172) Q4(n=171).Error bars indicate 90% confidence intervals.

Figure 3. Differences in postprandial measures across repeated meals within individuals

(n=1053, m=6428 (UK n=958; US n=95, m=500). Standardised breakfasts that were repeated on two occasions, following an overnight fast, separated by 2-5 days. The difference between the first and second repeat of each meal was calculated. We then measured the degree to which the difference in Glucose Dip2-3h was associated with the difference in each of the postprandial measures in the exploration and validation studies. For illustration, the results were grouped according to differences between the Glucose Dip2-3h recorded on the first and second repeat (<-10% less, -10% to +10%, >10% more). Number of pairs of meals foreach box are: for panels (a) and (b) <-10% less m= 177, -10% to +10% m=652, >10% more m=157; for panels (c) (d) and (e) <-10% less m= 501, -10% to +10% m=1960, >10% more m=503. Correlation coefficients (r) were calculated for m= 2964 and m=250 pairs of meals from the UK and US respectively. P-values from two sided tests are shown. Error bars indicate 90% confidence intervals.