Clinical trial NCT03844230: Role of Sweetness in Glucose Regulation
Official title: Role of Sweet Taste Signaling in Glucose Regulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Keywords: sweeteners
glucose metabolism
taste receptors
sucralose
Lead sponsor: University of Illinois at Urbana-Champaign
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
First posted: 2019-02-18
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Plasma Glucose
timeFrame: Up to 5 hours after drinking a glucose load
measure: Plasma Insulin
timeFrame: Up to 5 hours after drinking a glucose load
measure: Plasma C-Peptide
timeFrame: Up to 5 hours after drinking a glucose load
measure: Sensory Evaluation
timeFrame: Up to 2 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Champaign
country: United States
facility: University of Illinois at Urbana Champaign
state: Illinois
Study officials:
affiliation: University of Illinois at Urbana-Champaign
name: Marta Y Pepino, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1093/chemse/24.4.439.
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. doi: 10.1074/jbc.M414287200. Epub 2005 Jan 24.
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.
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: 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.