Role of Sweetness in Glucose Regulation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Role of Sweet Taste Signaling in Glucose Regulation

Conditions
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Obesity

Intervention / Treatment
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* Other: Control - Inhibition
* Other: Experimental I- Inhibition
* Other: Experimental II- Inhibition
* Other: Control- Stimulation
* Other: Experimental I- Stimulation
* Other: Experimental II- Stimulation
* Other: Sensory Evaluation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Inhibition Group<br>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). | Other: Control - Inhibition<br>* Taste and spit up water 10 minutes before drinking a glucose load<br>Other: Experimental I- Inhibition<br>* Taste and spit up water 10 minutes before drinking a glucose load mixed with lactisole<br>Other: Experimental II- Inhibition<br>* Taste and spit up sucralose 10 minutes before drinking a glucose load mixed with lactisole<br>Other: Sensory Evaluation<br>* Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold<br>|
| Other: Stimulation Group<br>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). | Other: Control- Stimulation<br>* Taste and spit up water 10 minutes before drinking a glucose load<br>Other: Experimental I- Stimulation<br>* Taste and spit up sucralose 10 minutes before drinking a glucose load<br>Other: Experimental II- Stimulation<br>* Drink sucralose 10 minutes before drinking a glucose load<br>Other: Sensory Evaluation<br>* Taste different solutions to evaluate sweet taste preference, suprathreshold intensity and detection threshold<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sweeteners, glucose metabolism, taste receptors, sucralose