Role of Sweetness in Glucose Regulation

Obesity Clinical Trial

— STS  

Official title:

Role of Sweet Taste Signaling in Glucose Regulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03844230
• Other study ID #: 19294
• Status: Recruiting
• Phase: N/A
• Start date: April 24, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: April 2021
• Source: University of Illinois at Urbana-Champaign
• Contact: Marta Y Pepino, PhD
• Phone: (217) 300-2374
• Email: ypepino[@]illinois.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Data from several studies show that consuming a diet high in low-calorie sweeteners (LCS), mainly in diet sodas, is linked to the same metabolic disorders as consuming a diet high in added sugars, including an increased risk of developing type 2 diabetes. Sweet taste receptors, once thought to be unique to the mouth, have now been discovered in other parts of the body, including the intestine and the pancreas, where they play a role in blood sugar control. These newly identified receptors provide new avenues to explore how LCS may affect metabolism and health. This project is designed to examine the role of sweet taste signaling, both in the mouth and in the gut, on blood sugar control and how habitual consumption of LCS may affect sweet taste signaling and metabolism in people with obesity.

Description:

The overall goal of this research is to assess the role of oral and gut sweetness signaling in postprandial glucose metabolism and to determine how acute and chronic low-calorie sweetener (LCS) consumption may affect this signaling in people with obesity. The aims will determine the independent and combined contributions of pharmacological inhibition (Aim 1) or extra stimulation (Aim 2) of sweet taste signaling in the gut, mouth, or both on hormonal responses to an oral glucose tolerance test (OGTT) in two groups of subjects with obesity: habitual and non-habitual LCS consumers. Validated sensory evaluation techniques will also ascertain subjects' taste perception (Aim 3) to test the hypotheses that habitual consumption of LCS blunts perception of sweetness and, in turn, affects postprandial glucose regulation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 40 Years

Eligibility

Inclusion Criteria:

• All races/ethnicities
• Habitual (> 5 diet sodas per week) and non-habitual (=1 diet soda or 1 packet of LCS per week) LCS consumers
• 30 = BMI <40 kg/m2
• Not severely insulin resistant (HOMA-IR2 < 2.6)

Exclusion Criteria:

• BMI < 30 and 40< BMI kg/m2
• HOMA-IR2>2.6
• Irregular LCS consumers (>1 diet sodas or packets of LCS per week but <5)
• Current smokers or quit smoking nicotine cigarettes for less than 6 months ago
• Pregnant, breastfeeding, menopausal
• Presence of anemia : <12g/dl for women and <13g/dl for men
• Blood donation in the past 8 weeks
• Presence of malabsorption syndrome
• History of bariatric surgery
• Presence of inflammatory intestinal disease, liver or kidney disease
• Have diabetes (fasting glucose level >126mg/dl or plasma glucose level 2h after glucose challenge >200 mg/dl)
• Taking any medication that might affect glucose metabolism or the results of our study

Related Conditions & MeSH terms

• Obesity

Intervention

Other:
• Control - Inhibition
Taste and spit up water 10 minutes before drinking a glucose load
• Experimental I- Inhibition
Taste and spit up water 10 minutes before drinking a glucose load mixed with lactisole
• Experimental II- Inhibition
Taste and spit up sucralose 10 minutes before drinking a glucose load mixed with lactisole
• Control- Stimulation
Taste and spit up water 10 minutes before drinking a glucose load
• Experimental I- Stimulation
Taste and spit up sucralose 10 minutes before drinking a glucose load
• Experimental II- Stimulation
Drink sucralose 10 minutes before drinking a glucose load
• Sensory Evaluation
Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold

Locations

Country	Name	City	State
United States	University of Illinois at Urbana Champaign	Champaign	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Illinois at Urbana-Champaign	Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (6)

Adams TB, Cohen SM, Doull J, Feron VJ, Goodman JI, Marnett LJ, Munro IC, Portoghese PS, Smith RL, Waddell WJ, Wagner BM; Expert Panel of the Flavor and Extract Manufacturers Association. The FEMA GRAS assessment of phenethyl alcohol, aldehyde, acid, and related acetals and esters used as flavor ingredients. Food Chem Toxicol. 2005 Aug;43(8):1179-206. Epub 2005 Jan 26. Review. — View Citation

Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, Benard LM, Osman R, Margolskee RF, Max M. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem. 2005 Apr 15;280(15):15238-46. Epub 2005 Jan 24. — View Citation

Karimian Azari E, Smith KR, Yi F, Osborne TF, Bizzotto R, Mari A, Pratley RE, Kyriazis GA. Inhibition of sweet chemosensory receptors alters insulin responses during glucose ingestion in healthy adults: a randomized crossover interventional study. Am J Clin Nutr. 2017 Apr;105(4):1001-1009. doi: 10.3945/ajcn.116.146001. Epub 2017 Mar 1. — View 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. — View Citation

Schiffman SS, Booth BJ, Sattely-Miller EA, Graham BG, Gibes KM. Selective inhibition of sweetness by the sodium salt of +/-2-(4-methoxyphenoxy)propanoic acid. Chem Senses. 1999 Aug;24(4):439-47. — View Citation

Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C. The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin Nutr. 2011 Aug;30(4):524-32. doi: 10.1016/j.clnu.2011.01.007. Epub 2011 Feb 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Glucose	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma glucose concentration	Up to 5 hours after drinking a glucose load
Primary	Plasma Insulin	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma insulin concentration	Up to 5 hours after drinking a glucose load
Primary	Plasma C-Peptide	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma C-peptide concentration	Up to 5 hours after drinking a glucose load
Primary	Sensory Evaluation	Participants will be tasting solutions containing different concentrations of glucose, sucrose and sucralose (some of the solutions will also have lactisole) to assess their detection threshold, sweet taste intensity and preference. They will have to rate the intensity of the solution on a general Labeled Magnitude Scale (gLMS) ranging from "no sensation" (0) to "strongest imaginable sensation" (100) and choose the solutions they prefer.	Up to 2 hours