The goal of this clinical trial is to evaluate the influence of parasympathetic transmission from the brain to different metabolic organs. This transmission can be blocked with the muscarinic antagonist atropine.
Participants will undergo an oral glucose tolerance test combined with a double tracer dilution technique either with atropine infusion or placebo.
Healthy individuals and high-risk individuals will be compared to identify possible changes in signaling in high-risk groups. In addition, men and women will be included to take into account possible sex differences.
Age: at least 18
BMI: 20 - 24.9 kg/m2 (for the healthy groups) or more than 28 kg/m2 (for the overweight groups)
For women: Hormonal contraception with a single-phase preparation (e.g. Nuvaring)
Understanding and voluntarily signing an informed consent form prior to study-related examinations
Drug and/or alcohol abuse
smoking
Taking medication that affects blood sugar or addresses the central and/or autonomic nervous system (e.g. anti-epileptic drugs, beta blockers, dopamine agonists, antidepressants). Taking antihistamines.
Pre-existing cardiac conditions
Crossover
Oral glucose tolerance test with double-tracer dilution and atropine infusion
Other interventionSubjects will undergo a 75 g oGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes, while the infusion will start 120 minutes prior the oGTT and will last until the end of the oGTT. Atropine infusion will be administered 20 minutes before the start of the oGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.
Oral glucose tolerance test with double-tracer dilution and saline infusion (placebo)
Other interventionSubjects will undergo a 75 g oGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes, while the infusion will start 120 minutes prior the oGTT and will last until the end of the oGTT. Saline infusion will be administered 20 minutes before the start of the oGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.
Glucose tolerance
Effect of parasympathetic blockade with atropine versus placebo on glucose tolerance assessed as area under the glucose curve (0-120 minutes) and glucose levels at timepoint 120 minutes during the 75 g oral glucose tolerance test.
Insulin Sensitivity
Effect of parasympathetic blockade with atropine versus placebo on insulin sensitivity assessed from glucose and insulin measurements during the 75 g oral glucose tolerance test.
Insulin Secretion
Effect of parasympathetic blockade with atropine versus placebo on insulin secretion assessed from glucose and insulin/C-peptide measurements during the 75 g oral glucose tolerance test.
Lipolysis
Effect of parasympathetic blockade with atropine versus placebo on the suppression of lipolysis during a 75 g oral glucose tolerance test.
Gastric emptying
Effect of parasympathetic blockade with atropine versus placebo on gastric emptying during the 75 g oral glucose tolerance test.
Amino Acid Metabolism
Effect of parasympathetic blockade with atropine versus placebo on amino acid metabolism assessed by amino acid measurements during the 75 g oral glucose tolerance test.
Bile acid metabolism
Effect of parasympathetic blockade with atropine versus placebo on bile acid metabolism assessed by bile acid measurements during the 75 g oral glucose tolerance test.
Circulating peptides
Effect of parasympathetic blockade with atropine versus placebo on circulating proteins/peptides during the 75 g oral glucose tolerance test.
Lipids and lipoproteins
Effect of parasympathetic blockade with atropine versus placebo on lipids and lipoproteins assessed by lipid measurements during the 75 g oral glucose tolerance test.
Metabolites
Effect of parasympathetic blockade with atropine versus placebo on circulating metabolites during the 75 g oral glucose tolerance test.
Immune cell composition
Effect of parasympathetic blockade with atropine versus placebo on immune cell composition assessed by flow cytometry during the 75 g oral glucose tolerance test.
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