description
SYNOPSIS
Rationale:
Nutrition science has had difficulty to demonstrate specific health-beneficial effects related to diet or dietary ingredients. One of the reasons is that in healthy subjects it is difficult to assess changes in health status. The response to challenges may be used to derive biomarkers for maintenance of physiological function and ultimately as indicator for prevention of (metabolic) diseases.
The current clinical study aims to investigate whether a high fat challenge test with generally available ingredients can be developed, which can quantify the adaptive capacities in the most relevant metabolic processes, and thus applicable for a broad range of functional foods and ingredients targeting these processes in the practice.
Objective:
• Primary Objective
To study the adaptive capacity in relevant metabolic processes after a high fat challenge (OLTT) and oral glucose challenge (OGTT) in healthy humans to determine the relevant parameters that react on these challenges. With the aim to develop a sensitive test method (or combinations of tests) that are generally applicable in clinical food research.
• Secondary Objective
To investigate whether the developed challenge test and defìned new biomarkers are feasible to demonstrate reduced adaptation in diabetic subjects compared to healthy subjects.
• ExplorativeObjective
- To investigate whether the challenge tests and defined new biomarkers are reproducible;
- To investigate the whether the metabolites measured by non-invasive methods such as breath air and saliva can reflect the adaptive capacity in the switch between the challenge tests.
Study Design and sample size:
This is an explorative randomized cross-over study in two groups of 20 male participants aged 30-55 One group will consist of 20 healthy male volunteers and the other group will consist of 20 male subjects with Type 2 Diabetes Mellitus (T2DM). Both groups will be given the OLTT or the OGTT at fasting condition on two different study days. Washout between study days will be at least 2 days. One subgroup of 10 subjects from healthy group will undergo a repeated OLTT challenge to assess variability of response in metabolic parameters over time. Furthermore, 10 healthy and 10 T2DM males will undergo a QUARK indirect calorimetry measurement to assess the metabolic flexibility.
Ten healthy and 10 T2DM males who are not subjected to QUARK indirect calorimetry measurement will undergo breath air and saliva sample collection. Five of each group will collect breath air while 5 others of each group will collect saliva.
Healthy is defined based on medical history evaluation, physical examination, results of the pre-study laboratory tests of biochemistry and HbA1c with a body mass index (BMl) of 20.0-25.0 kglm'.
T2DM is diagnosed according to the following criteria: 1) diagnosed as T2DM evidenced by a documented history and use prescription of one oral glucose-lowering drug; 2) BMI of T2DM is in the range of 25.1-30.0 kg/m2.
Experimental treatments:
Two dietary challenge tests will be applied: The OLTT is a drink of 500 mL which consists of a mixture of 75g glucose syrup, 20g Protifar (Nutricia), 60g palm oil and 64g water. The OGTT is a drink consisting of 75 g glucose in 300mL water.
Main Parameters:
On study days, t=0 (fasting) and 6 time-points (t=0.5, t=1, t=2, t=4, t=6 and t=8 hours) after challenge test, blood will be sampled from each subject to measure the markers of glucose metabolism (including but not restricted to glucagon, GLP-1, leptin, insulin), metabolic related (including but not restricted to, adiponectin, GIP, C-peptide, glutathione ratio), immunology (including but not restriced to, C reactive protein, serum amyloid A, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule) and metabolites measured by metabolomics technology (including but not restricted to, endogenous metabolites involved in energy metabolism, urea cycle, glucose metabolism, ketonbodies, lipid metabolism and amino acids). Moreover, gas exchange parameters including oxygen consumption and carbon dioxide production will be quantified by the QUARK indirect calorimeter to reflect the energy metabolism in order to establish the metabolic flexibility of subjects when the energy sources are switched between carbohydrate and lipids.
Objectives
• Primary Objective
To study the adaptive capacity in relevant metabolic processes after a high fat challenge (OLTT) and oral glucose challenge (OGTT) in healthy humans to determine the relevant parameters that react on these challenges. With the aim to develop a sensitive test method (or combinations of tests) that are generally applicable in clinical food research.
• Secondary Objective
To investigate whether the developed challenge test and defìned new biomarkers are feasible to demonstrate reduced adaptation in diabetic subjects compared to healthy subjects.
• ExplorativeObjective
- To investigate whether the challenge tests and defined new biomarkers are reproducible;
- To investigate the whether the metabolites measured by non-invasive methods such as breath air and saliva can reflect the adaptive capacity in the switch between the challenge tests.
Inclusion criteria
criteria Healthy persons:
- BMI between 20 and 25 kg/m2
criteria T2DM:
- BMI between 25.1 and 35 kg/m2
- Use of Metformine as antidiabetic medication
- Fasting glucose at screening exceeds 7.0 mmol/l
subjects stop the use of antidiabetic medication. Study starts within 3 days, to reduce the time subject are exposed to hyperglycaemie.
- Fasting glucose at screening below 7.0 mmol/l
subjects stop the use of antidiabetic medication. Rescreening after approximately 1 week, if fasting glucose exceeds 10mmol/l then Study starts within 3 days.
