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| ID | Type | Description | Link |
|---|---|---|---|
| 101125605 | Other Grant/Funding Number | European Research Council |
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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.
This research project aims to investigate to what extent the parasympathetic nervous system is responsible for the transmission of signals from the brain to peripheral organs. Furthermore, the study will investigate sex differences and differences between healthy and high-risk individuals on brain-derived coordination of postprandial signaling for metabolic control.
Therefore, parasympathetic blockade will be introduced by atropine infusion (on one day) versus saline infusion as placebo (on another day) in a randomized fashion. For safety reasons, only the participants will be blinded. Infusion will start 20 minutes before a 75 gram oral glucose tolerance test (oGTT) and last until the end of the 2h oGTT. The oGTT will introduce a postprandial state. Additionally, 1000 mg Paracetamol will be added to the solution to study gastric emptying.
This approach will be combined with a double-tracer dilution technique. Labeled glucose ([6,6-2H]glucose) will be infused 120 minutes before and during the oGTT (120 min) and will be used to address endogenous glucose production. The glucose drink from the oGTT will be enriched with [U-13C6]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atropine Infusion | Experimental | 5 µg x kg fat free mass-1 x h-1 |
|
| Saline infusion | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral glucose tolerance test with double-tracer dilution and atropine infusion | Other | Subjects 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 120 minutes |
| 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. | 120 minutes |
| 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. | 180 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Lipolysis | Effect of parasympathetic blockade with atropine versus placebo on the suppression of lipolysis during a 75 g oral glucose tolerance test. | 120 minutes |
| Gastric emptying | Effect of parasympathetic blockade with atropine versus placebo on gastric emptying during the 75 g oral glucose tolerance test. |
| Measure | Description | Time Frame |
|---|---|---|
| Circulating peptides | Effect of parasympathetic blockade with atropine versus placebo on circulating proteins/peptides during the 75 g oral glucose tolerance test. | 120 minutes |
| Lipids and lipoproteins |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Martin Heni, MD | Contact | +4973150044505 | martin.heni@uniklinik-ulm.de | |
| Andrea Geissler | Contact | andrea.geissler@uniklinik-ulm.de |
| Name | Affiliation | Role |
|---|---|---|
| Martin Heni, MD | Ulm University Hopital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ulm University Hospital | Recruiting | Ulm | 89081 | Germany |
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|
| Oral glucose tolerance test with double-tracer dilution and saline infusion (placebo) | Other | Subjects 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. |
|
| 120 minutes |
| 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. | 120 minutes |
| 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. | 120 minutes |
| Substrate oxidation | Effect of parasympathetic blockade with atropine versus placebo on substrate oxidation assessed by indirect calorimetry at timepoints -110 Minutes, 30 Minutes, 60 Minutes and 120 Minutes during the 75 g oral glucose tolerance test. | 230 Minutes |
| Incretin secretion | Effect of parasympathetic blockade with atropine versus placebo on incretin secretion during the 75 g oral glucose tolerance test. | 120 minutes |
| Sex differences | Explore sex differences in the effect of parasympathetic blockade with atropine versus placebo in the mentioned outcome measures. | 180 minutes |
| Autonomic nervous system | Effect of parasympathetic blockade with atropine versus placebo on the autonomic nervous system assessed by heart rate variability during the 75 g oral glucose tolerance test. | 180 minutes |
| Blood coagulation parameters | Influence of of parasympathetic blockade with atropine versus placebo on blood coagulation parameters. This is assessed through global coagulation tests and single coagulation factors. | 120 Minutes |
Effect of parasympathetic blockade with atropine versus placebo on lipids and lipoproteins assessed by lipid measurements during the 75 g oral glucose tolerance test.
| 120 minutes |
| Metabolites | Effect of parasympathetic blockade with atropine versus placebo on circulating metabolites during the 75 g oral glucose tolerance test. | 120 minutes |
| 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. | 120 minutes |
| Insulin clearance | Effect of parasympathetic blockade with atropine versus placebo on insulin clearance assessed from insulin and C-peptide measurements during the 75 g oral glucose tolerance test. | 120 minutes |
| Metabolic flexibility | Effect of parasympathetic blockade with atropine versus placebo on metabolic flexibility assessed by the change in respiratory quotient during the 75 g oral glucose tolerance test. | 180 minutes |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |
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