This project aims to compare the acute metabolic effects of the three sweeteners sucrose, glucose, and fructose on GI hormones (GLP-1, PYY, CCK, and ghrelin). Furthermore, glycemic control, erythritol and xylitol concentrations, blood coagulation function , blood lipids, uric acid, high-sensitive C-reactive protein (hsCRP), complete blood count, gastric emptying, appetite-related sensations, and GI symptoms will be investigated.
Sugar should not be defined by origin (added sugar, free sugar, simple sugar) but rather by chemical structure (sucrose, glucose, fructose, etc.). Although the disaccharide sucrose is hydrolysed by sucrase into its monosaccharides glucose and fructose, the administration of each of the three sweeteners alone results in different metabolic effects. Although sucrose, glucose, and fructose are long known sweeteners in food and beverages and their metabolic effects have been extensively studied, there are still no comprehensive studies comparing the three sweeteners in a whole range of parameters. The main inconsistency in the literature is the study design which influences the outcomes. It is important to differentiate whether it is an acute or chronic study, whether the participants are adults or children, are healthy or have T2DM, have normal weight, overweight or obesity, whether the dosage is chosen to be isocaloric or isosweet, whether there is a control group or whether the sweeteners are administered orally or intragastrical.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
20
St. Claraspital
Basel, Switzerland
RECRUITINGEffect of sucrose, glucose, fructose, and water on the GI hormone response - GLP-1
Plasma GLP-1 will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).
Time frame: Blood will be drawn at the following timepoints: : -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration)
Effect of sucrose, glucose, fructose, and water on the GI hormone response - PYY
PYY-3-36 will be quantified using a non-radioactive high sensitive sandwich ELISA (Millipore - # EZHPYYT66K).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effect of sucrose, glucose, fructose, and water on the GI hormone response - CCK
Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum (No. 92128)
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effect of sucrose, glucose, fructose, and water on the GI hormone response - Ghrelin
Octanoylated ghrelin will be measured by a radioimmunoassay with 125I \[Tyr24\] human ghrelin as tracer and a rabbit antibody against human ghrelin (final dilution 1/100000), which does not cross-react with desoctanoylated ghrelin.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma glucose
Glucose will be measured by a glucose oxidase method (Rothen Medizinische Laboratorien AG, Basel, Switzerland).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma insulin
Insulin will be quantified using a chemiluminescent microparticle immunoassay (chemiflex) reagent kit (#8k41; Abbott) and the relative light units detected by the ARCHITECT optical system (model: CI4100; Abbott).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma c-peptide
C-peptide will be measured with a commercially available sandwich ELISA kit from Millipore (Millipore - # EZHCP-20K).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma glucagon
Glucagon concentrations in plasma will be measured after extraction of plasma with 70% ethanol (vol/vol, final concentration). The antibody is directed against the C-terminus of the glucagon molecule (antibody code no. 4305) and therefore mainly measures glucagon of pancreatic origin.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on erythritol concentrations
Erythritol concentrations will be measured by GC-MS/MS (Gas Chromatography Tandem Mass Spectrometry).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on xylitol concentrations
Xylitol concentrations will be measured by GC-MS/MS (Gas Chromatography Tandem Mass Spectrometry).
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on blood coagulation function - p-selectin
Plasma concentrations of p-selectin will be measured using a commercially available ELISA-kit.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180 minutes (after administration).
Effects on blood coagulation function - sVCAM1
Plasma concentrations ofsVCAM1 will be measured using a commercially available ELISA-kit.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180 minutes (after administration).
Effects on blood coagulation function - PF-4
Plasma concentrations of PF-4 will be measured using a commercially available ELISA-kit.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180 minutes (after administration).
Effects on blood coagulation function - D-Dimers
D-Dimers will be measured using an antigen-test.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180 minutes (after administration).
Effects on blood lipids
Analyses of blood lipids are carried out in the hospital laboratory.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120 and 180 minutes (after administration).
Effects on uric acid
Analyses of uric acid are carried out in the hospital laboratory.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180 minutes (after administration).
Effects on hsCRP
Concentrations of hsCRP will be measured by Rothen Laboratory in Basel.
Time frame: Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, 90, 120, and 180minutes (after administration).
Effects on gastric emptying rate
Gastric emptying rate will be determined using a 13C-sodium acetate breath test.
Time frame: Breath samples will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 240minutes (after administration).
Effects on appetite-related sensations
Appetite perceptions (feelings of: a) hunger, b) satiety) are assessed by visual analogue scale (VAS). Visual analogue scales consist of a horizontal, unstructured, 10-cm line representing the minimum (0.0 points) to the maximum rating (10.0 points). Subjects assign a vertical mark across the line to indicate the magnitude of their subjective sensation at the present time point. The measurement is quantified by the distance from the left end of the line (minimum rating) to the subject's vertical mark.
Time frame: Visual analogue scales will be recorded at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 105, 120, and 180 minutes (after administration).
Effects on GI tolerance
GI symptoms will be assessed by use of a checklist including the following questions: abdominal pain, nausea, vomiting, diarrhoea, borborygmi, abdominal distension, eructation and increased flatus.
Time frame: GI tolerance will be recorded atthe following time points: -10 minutes (before administration) and 30, 60, 90,120, 180, and 240 minutes (after administration).
Bettina K Wölnerhanssen, Prof. Dr. med.
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