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. 2019 Dec 20;12(1):29.
doi: 10.3390/nu12010029.

Effects of Sucralose Ingestion Versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants With Normal Weight and Obesity: A Randomized Crossover Trial

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Free PMC article

Effects of Sucralose Ingestion Versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants With Normal Weight and Obesity: A Randomized Crossover Trial

Alexander D Nichol et al. Nutrients. .
Free PMC article

Abstract

Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20-40 min of the OGTT in normal-weight participants but increased within 90-120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.

Keywords: artificial sweeteners; glucose metabolism; insulin; low-calorie sweeteners; non-nutritive sweeteners; oral glucose tolerance test; sucralose.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
(a) Average difference in plasma glucose concentrations between water and sucralose treatment for all participants (normal-weight and obese groups combined). (b) Percent difference in the incremental area under the curve (iAUC) for glucose for each participant during the day they ingested sucralose compared with the day they ingested water 10 min before the glucose load in participants with normal weight (purple bars) and participants with obesity (blue bars).
Figure A2
Figure A2
Changes in insulin concentrations relative to the water treatment at each given time point for the sucralose treatment and for the sham-fed treatment in the group of participants with normal weight (n = 10, left panel) and with obesity (n = 11, right panel). 1 n = 9 participants for sucralose sham-fed condition in the obese group. The dotted line represents values which are identical to those in water treatment. * Value from sham-fed treatment significantly different from water treatment within body-weight group at p < 0.05. Value from same treatment significantly different between weight groups at p < 0.05.
Figure A3
Figure A3
Plasma glucose-dependent insulinotropic peptide (GIP) mean concentration in normal-weight participants (n = 10; left panel) and participants with obesity (n = 11; right panel) after sucralose, water, or sham-fed treatment 10 min before ingestion of a 75 g glucose load at time 0 min. 1 n = 9 participants for sucralose sham-fed condition in the obese group. The general linear mixed model (PROC MIXED) analysis with subject-level random intercepts was used. Treatment (water, sucralose, and sham-fed), time, and weight group (normal-weight and obese), as well as all interactions, were included in the model and treated as fixed effects. Post hoc Fisher least significant difference was used when values were statistically significant. * Value from sucralose treatment significantly different from corresponding water treatment, p < 0.05; Value from sucralose treatment significantly different from sham-fed treatment, p < 0.05. Data are presented as the mean ± SEM.
Figure A4
Figure A4
Insulin secretion rate (ISR) in response to a glucose load in normal-weight participants (n = 10; left panel) and participants with obesity (n = 11; right panel) after sucralose, water, or sham-fed treatment 10 min before ingestion of a 75 g glucose load at time 0 min. 1 n = 9 participants for sucralose sham-fed condition in the obese group. ISR is partitioned in its dynamic (top panels) and static (bottom panels) components. The general linear mixed model (PROC MIXED) analysis with subject-level random intercepts was used. Treatment (water, sucralose, and sham-fed), time, and weight group (normal-weight and obese), as well as all interactions, were included in the model and treated as fixed effects. Post hoc Fisher least significant difference was used when values were statistically significant. * Value from sucralose treatment significantly different from corresponding water treatment, p < 0.05. Data are presented as the mean ± SEM.
Figure A5
Figure A5
Oral glucose rate of appearance in systemic circulation and endogenous glucose production rate in normal-weight participants (n = 10; left panel) and participants with obesity (n = 11; right panel) after sucralose, water, or sham-fed treatment prior to ingestion of a 75 g glucose load at time 0 min. 1 n = 9 participants for sucralose sham-fed condition in the obese group. The general linear mixed model (PROC MIXED) analysis with subject-level random intercepts was used. Treatment (water, sucralose, and sham-fed), time, and weight group (normal-weight and obese), as well as all interactions, were included in the model and treated as fixed effects. Post hoc Fisher least significant difference was used when values were statistically significant. Data are presented as the mean ± SEM.
Figure 1
Figure 1
Study design flow diagram. * Because the PROC MIXED analysis can handle unbalanced designs, data from the two participants who did not complete one of the study visits were also included.
Figure 2
Figure 2
Plasma glucose, insulin, C-peptide concentrations, and total glucose rate of appearance into systemic circulation in participants with normal weight (n = 10; left panels) and participants with obesity (n = 11; right panels) after ingesting either sucralose or water or tasting but not swallowing sucralose (sham-fed) 10 min before ingesting a drink containing 75 g glucose at time 0 min. 1 n = 9 participants for sucralose sham-fed condition in the obese group. The general linear mixed model (PROC MIXED) analysis, which can handle an unbalanced designed, was used. Treatment (water, sucralose, and sham-fed), time, and weight group (normal weight and obese), as well as all interactions were included in the model and treated as fixed effects and subject was included as random effect. Post hoc Fisher least significant difference was used when interactions were statistically significant. * Value from sucralose treatment significantly different from corresponding water treatment, p < 0.05; † Value from sham-fed treatment significantly different from corresponding water treatment, p < 0.05; ‡ Value from sucralose treatment significantly different from corresponding sham-fed treatment, p < 0.05. All values are the mean ± SEM.
Figure 3
Figure 3
Oral glucose rate of appearance into the systemic circulation (top panel) and endogenous glucose production rate (bottom panel) after ingesting either sucralose or water or tasting but not swallowing sucralose (sham-fed) 10 min before ingesting a drink containing 75 g glucose at time 0 min. The general linear mixed model (PROC MIXED) analysis, which can handle an unbalanced designed, was used. Treatment (water, sucralose, and sham-fed), time, and weight group (normal- weight, n = 10, and obese, n = 11), as well as all interactions were included in the model and treated as fixed effects and subject was included as random effect. Post hoc Fisher least significant difference was used when values were statistically significant. * Value from group with obesity significantly different from group with normal weight, p < 0.05. All values are the mean ± SEM.
Figure 4
Figure 4
Plasma sucralose concentrations in normal-weight participants (n = 10) and participants with obesity (n = 10) after sucralose treatment prior to ingestion of a 75 g glucose load at time 0 min. The general linear mixed model (PROC MIXED) analysis with subject-level random intercepts was used. Time and weight group (normal weight and obese), as well as the interaction, were included in the model and treated as fixed effects. Post hoc Fisher least significant difference was used when values were statistically significant. * Value for participants with obesity different from normal-weight participants, p < 0.05. All values are the mean ± SEM.

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