Are there interindividual differences in the reactive hypoglycaemia response to breakfast? A replicate crossover trial

Abstract

Background: Following consumption of a meal, circulating glucose concentrations can rise and then fall briefly below the basal/fasting concentrations. This phenomenon is known as reactive hypoglycaemia but to date no researcher has explored potential inter-individual differences in response to meal consumption.

Objective: We conducted a secondary analysis of existing data to examine inter-individual variability of reactive hypoglycaemia in response to breakfast consumption.

Methods: Using a replicate crossover design, 12 healthy, physically active men (age: 18-30 y, body mass index: 22.1 to 28.0 kg⋅m^{- 2}) completed two identical control (continued overnight fasting) and two breakfast (444 kcal; 60% carbohydrate, 17% protein, 23% fat) conditions in randomised sequences. Blood glucose and lactate concentrations, serum insulin and non-esterified fatty acid concentrations, whole-body energy expenditure, carbohydrate and fat oxidation rates, and appetite ratings were determined before and 2 h after the interventions. Inter-individual differences were explored using Pearson's product-moment correlations between the first and second replicates of the fasting-adjusted breakfast response. Within-participant covariate-adjusted linear mixed models and a random-effects meta-analytical approach were used to quantify participant-by-condition interactions.

Results: Breakfast consumption lowered 2-h blood glucose by 0.44 mmol/L (95%CI: 0.76 to 0.12 mmol/L) and serum NEFA concentrations, whilst increasing blood lactate and serum insulin concentrations (all p < 0.01). Large, positive correlations were observed between the first and second replicates of the fasting-adjusted insulin, lactate, hunger, and satisfaction responses to breakfast consumption (all r > 0.5, 90%CI ranged from 0.03 to 0.91). The participant-by-condition interaction response variability (SD) for serum insulin concentration was 11 pmol/L (95%CI: 5 to 16 pmol/L), which was consistent with the τ-statistic from the random-effects meta-analysis (11.7 pmol/L, 95%CI 7.0 to 22.2 pmol/L) whereas effects were unclear for other outcome variables (e.g., τ-statistic value for glucose: 0 mmol/L, 95%CI 0.0 to 0.5 mmol/L).

Conclusions: Despite observing reactive hypoglycaemia at the group level, we were unable to detect any meaningful inter-individual variability of the reactive hypoglycaemia response to breakfast. There was, however, evidence that 2-h insulin responses to breakfast display meaningful inter-individual variability, which may be explained by relative carbohydrate dose ingested and variation in insulin sensitivity of participants.

Keywords: Breakfast; Carbohydrate; Glucose; Metabolism; Response heterogeneity.

Fig. 1

Correlation between the replicates of the baseline-to-two-h response to breakfast minus the fasting control condition, for blood glucose (A), serum insulin (B), blood lactate (C), and serum NEFA concentrations (D). “Response 1” corresponds to the first pair of conditions (breakfast 1 minus control 1) and “Response 2” to the second pair of conditions (breakfast 2 minus control 2). Each data point is an individual participant. The dotted lines represent the MCID and the solid lines represent the group mean. n = 11. MCID, minimal clinically important difference. NEFA, non-esterified fatty acid

Fig. 2

Results of the meta-analysis of each participants treatment effect estimate for blood glucose (A), serum insulin (B), blood lactate (C), and serum NEFA concentrations (D) two h after consumption of breakfast (BREAKFAST) relative to two h after remaining in the overnight fasted state (FASTED). n = 11. NEFA, non-esterified fatty acid

Fig. 3

Correlation between the replicates of the baseline-to-two-h response to breakfast minus the fasting control condition, for whole-body energy expenditure (A), carbohydrate oxidation (B), and fat oxidation (C). “Response 1” corresponds to the first pair of conditions (breakfast 1 minus fasting 1) and “Response 2” to the second pair of conditions (breakfast 2 minus fasting 2). Each data point is an individual participant. The dotted lines represent the MCID and the solid lines represent the group mean. n = 12. MCID, minimal clinically important difference

Fig. 4

Results of the meta-analysis of each participants treatment effect estimate for whole-body energy expenditure (A), carbohydrate oxidation (B), and fat oxidation rates (C) two h after consumption of breakfast (BREAKFAST) relative to two h after remaining in the overnight fasted state (FASTED). n = 12

Fig. 5

Correlation between the replicates of the baseline-to-two-h response to breakfast minus the fasting control condition, for hunger (A), prospective consumption (B), fullness (C), and satisfaction ratings. “Response 1” corresponds to the first pair of conditions (breakfast 1 minus fasting 1) and “Response 2” to the second pair of conditions (breakfast 2 minus fasting 2). Each data point is an individual participant. The dotted lines represent the MCID and the solid lines represent the group mean. n = 12. MCID, minimal clinically important difference

Fig. 6

Results of the meta-analysis of each participants treatment effect estimate for hunger (A), prospective consumption (B), fullness (C), and satisfaction ratings (D) two h after consumption of breakfast (BREAKFAST) relative to two h after remaining in the overnight fasted state (FASTED). n = 12