Role of Sweetness in Glucose Regulation

Not Applicable

• Conditions: Obesity
• Interventions: Other: Control - Inhibition; Other: Control- Stimulation; Other: Experimental I- Inhibition; Other: Experimental I- Stimulation; Other: Experimental II- Inhibition; Other: Experimental II- Stimulation; Other: Sensory Evaluation

• Registration Number: NCT03844230
• Lead Sponsor: University of Illinois at Urbana-Champaign

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.

Study Timeline

• Study First Submitted: 2019-01-29
• Study First Submitted QC: 2019-02-13
• Study First Posted: 2019-02-18
• Study Start: 2019-04-24
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-26
• Last Update Posted: 2021-04-27
• Primary Completion: 2022-11-30
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Inhibition Group	Experimental I- Inhibition	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).
Inhibition Group	Experimental II- Inhibition	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).
Inhibition Group	Sensory Evaluation	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).
Stimulation Group	Experimental II- Stimulation	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).
Stimulation Group	Sensory Evaluation	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).
Inhibition Group	Control - Inhibition	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).
Stimulation Group	Control- Stimulation	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).
Stimulation Group	Experimental I- Stimulation	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).

Primary Outcome Measures

Name	Time	Method
Sensory Evaluation	Up to 2 hours	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.
Plasma Glucose	Up to 5 hours after drinking a glucose load	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma glucose concentration
Plasma Insulin	Up to 5 hours after drinking a glucose load	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma insulin concentration
Plasma C-Peptide	Up to 5 hours after drinking a glucose load	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma C-peptide concentration

Trial Locations

Locations (1)

University of Illinois at Urbana Champaign; 🇺🇸 Champaign, Illinois, United States