Background:
Epidemiological studies indicate that a high habitual intake of non-caloric artificial sweeteners (NAS) increases the risk of type 2 diabetes (T2DM), but the mechanisms are unknown. NAS exposure acutely activates intestinal sweet taste receptors (STRs) to release glucose-dependent insulinotropic polypeptide (GIP) from proximal K-cells, and glucagon-like peptide-1 and 2 (GLP-1, GLP-2) from distal L‑cells in animals, while chronic NAS exposure augments glucose absorption and increases postprandial glycaemia. It is not known whether NAS alters glucose absorption or postprandial glycaemia in humans.
Methods:
27 healthy lean subjects (age 27 ± 2 years, 14 male) were randomised, in double-blind fashion, to NAS supplementation (92 mg sucralose + 52 mg acesulfame-K, N=14) or placebo (N=13), taken in capsules three times daily before meals over 2 weeks. Fasted subjects underwent endoscopy incorporating a 30 min intraduodenal glucose infusion (30g/150ml, 3 kcal/min, including 3g of the glucose analogue 3-O-methyl glucose, 3‑OMG), and biopsy collection, before and immediately after the intervention. Glucose absorption (serum 3‑OMG), plasma glucose, insulin and gut peptides (total GLP-1, GLP-2 and GIP) were measured over 120 min.
Results:
NAS supplementation augmented glucose absorption (23%, P ≤ 0.05) and blood glucose during enteral glucose (27%, P ≤ 0.05), and attenuated GLP-1 release compared to baseline (35%, P ≤ 0.05); none of these measures were altered with placebo. GIP responses were similar between groups, while GLP-2 and insulin were lower at 40 and 60 min in the NAS group (37% for both vs. baseline, P ≤ 0.05).
Conclusion:
NAS supplementation in healthy humans (i) enhances glucose absorption, (ii) augments blood glucose responses to enteral glucose, and (iii) attenuates GLP-1 release, the latter which may reflect reduced glucose exposure to distal L-cells. NAS may have a deleterious impact on acute glycaemic control in humans, which could predispose to T2DM.