Potential metabolic effect of sucralose following an oral glucose load in subjects with obesity and normal-weight subjects

Objective: Whether sucralose, the most commonly used non-nutritive sweetener (NNS), affects glucose metabolism in people is unclear. It has been reported that, when consumed acutely before an oral glucose tolerance test (OGTT), sucralose enhances insulinemic responses and decreases insulin sensitivity in subjects with obesity who are not regular consumers of NNS. However, studies in normal-weight adults, none of which control for use of NNS, found sucralose does not affect insulin responses to the ingestion of glucose or other carbohydrates. The objectives of the current study are to determine if those effects of sucralose can be replicated in subjects with obesity, are generalizable to normal-weight subjects when controlling for history of NNS use, and are caused merely by the sweet taste of sucralose (i.e., sham-feeding). In addition, with the aim of identifying potential mechanisms by which sucralose may decrease postprandial insulin sensitivity, we here investigated whole-body glucose kinetics by using a dual-tracer approach. Finally, we tested the hypothesis that, due to the compromised intestinal permeability associated with obesity, sucralose consumption is associated with higher plasma sucralose concentrations in people with obesity. Research Design and Methods: Ten normal-weight subjects (BMI: 22.8 ± 0.9 kg/m2) and nine subjects with obesity (BMI: 37.7 ± 6.1 kg/m2), all non-regular users of NNS, non-diabetic, and without significant insulin resistance (based on a homeostatic model assessment of insulin resistance score < 3), underwent a 5-hour modified OGTT in which ingested glucose was labeled with one tracer while a second glucose tracer was infused intravenously at a constant rate on three separate testing days. Each testing day differed only by which pre-load solution (water ingestion (control condition), sucralose ingestion (experimental condition), or sucralose sham-fed (taste condition)) was administered 10 minutes prior to the OGTT in a randomized crossover design. Blood samples were taken throughout observation to determine plasma glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), glucose tracer-to-tracee ratio, and sucralose concentrations. Results: In subjects with obesity, compared to the control condition, sucralose sham-feeding reduced insulin and C-peptide concentrations within the first hour of the OGTT (both p-values ≤ 0.05), whereas sucralose ingestion increased plasma C-peptide incremental area under the curve (iAUC) by 22 ± 10% (p 0.19). Conclusions: These data demonstrate that sucralose differentially affects hormonal responses to an oral glucose load in subjects with obesity and normal weight subjects. Sucralose ingestion (not merely its taste) increases insulin secretion to an oral glucose load and transiently reduces glucose Rd in people with obesity, but not in normal-weight subjects. These findings support the hypothesis that sucralose may have adverse effects on glucose metabolism in people with obesity, which is the group that most frequently consumes NNS to facilitate weight management. These data also underscore a physiological role for sweetness perception in glucose homeostasis, which supports the notion that sweetness, regardless of an associated caloric contribution, should be consumed in moderation.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste