Clinical trial NCT02589002: Effects of Sucralose on Glucose Metabolism
Official title: Effects of Sucralose on Insulin Sensitivity, Pancreatic Response and Appetite Regulating Hormones
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Metabolism Disorders
Keywords: sucralose
insulin sensitivity
beta-cell response
appetite regulating hormone
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Two weeks
Secondary outcomes:
measure: Glucagon like peptide (GLP-1) change
timeFrame: Two weeks
measure: Ghrelin change
timeFrame: Two weeks
measure: Tyrosine-tyrosine peptide (PYY) change
timeFrame: Two weeks
measure: Leptin change
timeFrame: Two weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Distrito Federal
Study officials:
affiliation: Attending Physician
name: Paloma Almeda-Valdes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.