Immediate and Long-term Induction of Incretin Release by Artificial Sweeteners 1

Study Overview
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Brief Summary
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Epidemiological data suggest, that not only sugar-based, but also artificially sweetened soft drinks may play a role in the development of diabetes. Recent studies in animals and humans have shown, that artificial sweeteners (AS) influence metabolic responses after glucose ingestion, possibly alter the intestinal microbiome and even modulate incretin release. However, it is unclear, if these findings are valid for all kinds of AS, as they are chemically different. Furthermore, data on human subjects are sparse and controversial. The investigators will therefore conduct 7 consecutive single oral stimulations with glucose or AS alone or a combination. Three different AS will be tested.

Detailed Description
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Epidemiological data suggest, that not only sugar-based, but also artificially sweetened soft drinks may play a role in the development of diabetes. Recent studies in animals and humans have shown, that artificial sweeteners (AS) influence metabolic responses after glucose ingestion, possibly alter the intestinal microbiome and even modulate incretin release. However, it is unclear, if these findings are valid for all kinds of AS, as they are chemically different. Up to now, no single study has ever compared metabolic responses to different AS in the same subjects. Furthermore, data on human subjects are sparse and controversial. This is partially explained by different methodical approaches such as intragastral/intraduodenal application of AS, rather than conventional oral consumption. The investigators will therefore conduct 7 consecutive single oral stimulations with glucose or AS alone or a combination. Three different AS will be tested: saccharin, aspartame and sucralose.

Official Title
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Immediate and Long-term Induction of Incretin Release by Artificial Sweeteners 1

Conditions
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Pre-diabetes, Diabetes

Intervention / Treatment
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* Other: oral stimulation glucose
* Other: oral stimulation saccharin
* Other: oral stimulation aspartame
* Other: oral stimulation sucralose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy Exclusion Criteria: metabolic disorders such as diabetes, hypothyroidism, corticoid therapy, heart or lung disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucose only<br>oral ingestion of 54 g Glucose in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation glucose<br>* oral stimulation with glucose, AS or glucose+AS in fasted state, blood samples from fasted state up to 120 min post-ingestion<br>|
| Active Comparator: Glucose + Saccharin<br>oral ingestion of 54 g Glucose + 0,112 g Saccharin in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation glucose<br>* oral stimulation with glucose, AS or glucose+AS in fasted state, blood samples from fasted state up to 120 min post-ingestion<br>Other: oral stimulation saccharin<br> <br> |
| Active Comparator: Saccharin only<br>oral ingestion of 0,112 g Saccharin in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation saccharin<br> <br> |
| Active Comparator: Glucose + Aspartame<br>oral ingestion of 54 g Glucose 0,197 g Aspartame in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation glucose<br>* oral stimulation with glucose, AS or glucose+AS in fasted state, blood samples from fasted state up to 120 min post-ingestion<br>Other: oral stimulation aspartame<br> <br> |
| Active Comparator: Aspartame only<br>oral ingestion of 0,197 g Aspartame in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation aspartame<br> <br> |
| Active Comparator: Glucose + Sucralose<br>oral ingestion of 54 g Glucose + 0,088 g Sucralose in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation glucose<br>* oral stimulation with glucose, AS or glucose+AS in fasted state, blood samples from fasted state up to 120 min post-ingestion<br>Other: oral stimulation sucralose<br> <br> |
| Active Comparator: Sucralose only<br>oral ingestion of 0,088 g Sucralose in 300 ml water at t=0 in fasted state; blood samples over 120 mins | Other: oral stimulation sucralose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in GIP release | comparison between all seven interventions | 120 mins | 
| change in GLP-1 release | comparison between all seven interventions | 120 mins | 
| change in GLP-2 release | comparison between all seven interventions | 120 mins | 
| change in PYY release | comparison between all seven interventions | 120 mins | 
| change in insulin release | comparison between all seven interventions | 120 mins | 
| change in combined blood levels of glucose and insulin, expressed in calculated indices for insulin secretion | comparison between all seven interventions | 120 mins | 
| change in combined blood levels of glucose and insulin, expressed in calculated indices for insulin sensitivity | comparison between all seven interventions | 120 mins | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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incretin release