Role of Sweetness in Glucose Regulation

NCT ID: NCT03844230

Last Updated: 2021-04-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-24
• Study Completion Date: 2022-12-31

Brief 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.

Detailed 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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Inhibition Group

Randomly selected habitual and non habitual LCS consumers will be assessed on three different oral glucose tolerance test conditions (i.e. Control - Inhibition, Experimental I- Inhibition, Experimental II- Inhibition). A separate visit will evaluate their sweet taste perception and preferences (Sensory evaluation).

Group Type: OTHER

Control - Inhibition

Intervention Type: OTHER

Taste and spit up water 10 minutes before drinking a glucose load

Experimental I- Inhibition

Intervention Type: OTHER

Taste and spit up water 10 minutes before drinking a glucose load mixed with lactisole

Experimental II- Inhibition

Intervention Type: OTHER

Taste and spit up sucralose 10 minutes before drinking a glucose load mixed with lactisole

Sensory Evaluation

Intervention Type: OTHER

Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold

Stimulation Group

Randomly selected habitual and non habitual LCS consumers will be assessed on three different oral glucose tolerance test conditions (i.e. Control - Stimulation, Experimental I- Stimulation, Experimental II -Stimulation). A separate visit will evaluate their sweet taste perception and preferences (Sensory evaluation).

Group Type: OTHER

Control- Stimulation

Intervention Type: OTHER

Taste and spit up water 10 minutes before drinking a glucose load

Experimental I- Stimulation

Intervention Type: OTHER

Taste and spit up sucralose 10 minutes before drinking a glucose load

Experimental II- Stimulation

Intervention Type: OTHER

Drink sucralose 10 minutes before drinking a glucose load

Sensory Evaluation

Intervention Type: OTHER

Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold

Interventions

Control - Inhibition

Taste and spit up water 10 minutes before drinking a glucose load

Intervention Type: OTHER

Experimental I- Inhibition

Taste and spit up water 10 minutes before drinking a glucose load mixed with lactisole

Intervention Type: OTHER

Experimental II- Inhibition

Taste and spit up sucralose 10 minutes before drinking a glucose load mixed with lactisole

Intervention Type: OTHER

Control- Stimulation

Taste and spit up water 10 minutes before drinking a glucose load

Intervention Type: OTHER

Experimental I- Stimulation

Taste and spit up sucralose 10 minutes before drinking a glucose load

Intervention Type: OTHER

Experimental II- Stimulation

Drink sucralose 10 minutes before drinking a glucose load

Intervention Type: OTHER

Sensory Evaluation

Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of Illinois at Urbana-Champaign

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marta Y Pepino, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Urbana-Champaign

Locations

University of Illinois at Urbana Champaign

Champaign, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marta Y Pepino, PhD

Role: CONTACT

ypepino@illinois.edu

(217) 300-2374

Clara Salame, MSc, RD

Role: CONTACT

csalame2@illinois.edu

(217) 300-4709

Facility Contacts

Marta Y Pepino, MSc, RD

Role: primary

ypepino@illinois.edu

217-300-2374

Clara Salame, MSc, RD

Role: backup

csalame2@illinois.edu

2178192820

References

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. doi: 10.1016/j.fct.2004.11.013. Epub 2005 Jan 26.

Reference Type: BACKGROUND

PMID: 15950814 (View on PubMed)

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. doi: 10.1093/chemse/24.4.439.

Reference Type: BACKGROUND

PMID: 10480680 (View on PubMed)

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. doi: 10.1074/jbc.M414287200. Epub 2005 Jan 24.

Reference Type: BACKGROUND

PMID: 15668251 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28251932 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23633524 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21324568 (View on PubMed)

Other Identifiers

19294

Identifier Type: -

Identifier Source: org_study_id