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The primary aim of the present study is to study the effect of adrenaline administration on inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory proteins). Secondary objectives consist of the effect of adrenaline on atherogenic parameters.
Researchers will compare 2 groups, healthy individuals versus people with diabetes type 1 to see if the inflammatory reaction to adrenaline differs between these two groups.
Objective: The aim of the present study is to study the effect of increased adrenaline levels on the inflammatory response (e.g. leukocyte phenotype, cytokines, inflammatory proteins) by administering exogenous adrenaline in participants with type 1 diabetes and healthy participants.
Potentially eligible adult ( 16 - 75 years) participants will be recruited from the diabetes clinic at the department of internal medicine from the Radboud University Medical Center. Healthy participants will be recruited through social media and other advertisements. We will recruit a total of 30 individuals, i.e. 15 healthy participants and 15 people with type 1 diabetes. Participants with type 1 diabetes will be equipped with a blinded continuous glucose monitoring device (CGM) during the test, which will measure interstitial glucose levels for a total of 10 days.
Intervention: All participants will receive intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180 minutes, 24 hours 72 hours and a week after start of infusion. The blood samples will be used for phenotyping of the innate immune system and measuring inflammatory and atherogenic parameters. Throughout the infusion, vital parameters will be monitored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| People with type 1 diabetes | Experimental | The participants with type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. |
|
| Healthy individuals | Active Comparator | The participants without type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adrenaline | Drug | Adrenaline infusion at a rate of 0.04ug/kg/min for 1 hour administered intravenously. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Monocyte count | The amount of monocytes following 60 minutes of adrenaline infusion compared to baseline to asses the adrenaline effect on the inflammatory response. | Change from baseline compared to after 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Leukocyte count | Measurement of the amount of leukocytes | Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion |
| Leukocyte phenotype | Measuring several phenotypes by using a pre-defined panel of interest with flow-cytometry ( e.g. NK-cells, granulocytes) |
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Overall inclusion criteria:
Diabetes group specific criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cees Tack, MD. PHD. | Radboud University Medical Center (Radboudumc) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud UMC | Nijmegen | Gelderland | 6525GA | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41611977 | Derived | Mustafajev IF, Hendriksz MS, Stienstra R, Tack CJ, de Galan BE, Meijer RI. Adrenaline is a prominent driver of inflammatory responses following hypoglycaemia. Diabetologia. 2026 Jun;69(6):1675-1685. doi: 10.1007/s00125-026-06667-9. Epub 2026 Jan 29. |
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WE will share the study protocol using a data respository accesible through the research team on demand. Starting around 6 months after publication.
6 months after publication
The coordinating researcher will review acces requests. Seeing as the data are all anonimised acces will be granted for additional research in the field of inflammation or diabetes.
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D004837 | Epinephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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All participants will receive intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180 minutes, 24 hours 72 and a week after start of infusion. These samples will be used for phenotyping of the innate immune system and measuring inflammatory and atherogenic parameters. Throughout the infusion vital parameters will be monitored.
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|
| Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion |
| Pro-inflammatory proteins | Pro-inflammatory proteins using Olink Proteomics AB inflammation panel with 92 circulating inflammatory proteins ( e.g. EN-rage, FIT3L) | Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion |
| Inflammation plasma parameters | Inflammatory plasma protein using ELISA, ( e.g high sensitive-crp) | Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion |
| Atherogenic parameters | Atherogenic parameters using ELISA method including but not limited to, VCAM-1, ICAM-1, E-Selectin, P-selectin, PAI-1, Plasma Endothelin | Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion |
| Insulin | Plasma levels of insulin | Change from baseline at, 60 and 180 minutes |
| Adrenaline | Plasma levels of adrenaline | Change from baseline at 30, 60 and 180 minutes |
| Noradrenaline | Plasma levels of noradrenaline | Change from baseline at 30, 60 and 180 minutes |
| Glucose variability | Glucose variability measured by the blinded continuous glucose monitor including but not limited to, measuring time within range, amount of hypoglycaemic events, amount of hyperglycaemic events. | 2 weeks |
| Ex vivo cytokines | Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated monocytes, including TNF-α, IL-6, IL-10 and IL-1β. | Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion |
| Distribution of monocyte subset | Distribution of pro- and anti-inflammatory monocyte subsets using FACS (Fluorescence-activated Cell Sorting) | Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |