Effects of Sucralose on Glucose Metabolism (Sucralose)

In this study the effects of sucralose on insulin sensitivity, beta-cell response and appetite regulating hormones will be evaluated.

The consumption of non-nutritive sweeteners has a high prevalence. The effect of non-nutritive sweeteners in both beta-cell function and insulin resistance it is unknown. Previous studies performed in animal models and humans with diverse characteristics have shown variable effects of different non-nutritive sweeteners in variables related to glucose metabolism. Due to the high consumption of non-nutritive sweeteners it is relevant to know its effect in beta cell-function and insulin sensitivity. In this study the effects of sucralose, a non-nutritive sweetener that is highly consumed in the population, on insulin sensitivity and beta-cell function will be evaluated. 54 participants with normal glucose tolerance, normal weight, and without chronic diseases with a low consumption of non-nutritive sweeteners will be included. The participants will be randomly assigned to consume sucralose or to a control group. During the first visit an oral glucose tolerance test with 75 g of glucose will be performed. Fasting and 2-hour glucose will be measured in order to rule-out diabetes, abnormal fasting glucose, or glucose intolerance. During the second visit a three-hour IV glucose tolerance test will be performed administering 0.3 g/kg of glucose and insulin 0.03 U/kg. Samples will be taken following the minimal model described by Bergman. After this visit, the group assigned to receive sucralose will ingest 15% of the adequate daily intake (ADI) of sucralose and the control group will abstain of any non-nutritive sweetener consumption during 14 days. At the end of this period a third visit to repeat the IV glucose tolerance test will be performed. Samples will be analyzed measuring glucose and insulin concentrations to evaluate acute insulin response (AIR), glucose effectiveness (SG), first phase pancreatic response (ф1), and second phase pancreatic response (ф2). In addition, hormones involved in appetite and satiety (leptin, ghrelin, and peptide tyrosine tyrosine) will be quantified at the beginning and end of the intervention.

Insulin sensitivity and pancreatic response estimated with the minimal model using a frequently sampled IV glucose tolerance test

Inclusion Criteria: both genders age between 18 and 55 years body mass index ≥18.5 and <25 kg/m2 low consumption of non-nutritive sweeteners Exclusion Criteria: diabetes or glucose intolerance consumption of medications affecting insulin sensitivity (metformin, steroids, hormone replacement therapy, contraceptives) intestinal disease such as malabsorption or previous intestinal resection history of bariatric surgery pregnancy or lactation weight loss greater than 5% in the previous month

Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

Brown RJ, Walter M, Rother KI. Effects of diet soda on gut hormones in youths with diabetes. Diabetes Care. 2012 May;35(5):959-64. doi: 10.2337/dc11-2424. Epub 2012 Mar 12.

Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013 Sep;36(9):2530-5. doi: 10.2337/dc12-2221. Epub 2013 Apr 30.

Romo-Romo A, Aguilar-Salinas CA, Brito-Cordova GX, Gomez-Diaz RA, Almeda-Valdes P. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am J Clin Nutr. 2018 Sep 1;108(3):485-491. doi: 10.1093/ajcn/nqy152.