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In this study the investigators will investigate the glucose-independent effects of exogenous glucagon on insulin secretion and cognitive function in healthy subjects.
Subjects will participate in two study days. The first study day is with a 240-minute infusion of glucagon and the second study day is with an infusion of glucose (clamped to match the glucose levels measured during the glucagon infusion). During the study day, blood samples will be drawn frequently and cognitive testing will be performed.
The investigators will investigate glucagon's glucose-independent effects on insulin secretion and cognitive function by comparing plasma measures of C-peptide and cognitive test scores between the glucagon study day and the glucose clamp study day.
Five-ten subjects with normal health will be included, and each subject will participate in two study days.
Participants will arrive after an overnight fast and will be placed in a hospital bed in a semi-recumbent position. In each antecubital vein an intravenous catheter will be placed; one for administration of glucagon or glucose and one for blood sampling. The first study day will be the glucagon study day. The blood measurements of glucose from the glucagon study day will be used for clamping the glucose levels during the glucose clamp study day.
Baseline blood samples will be drawn. At time 0 minutes the infusion of glucagon or glucose will be initiated. Glucagon will be infused at a rate of 10ng/kg/min. Blood glucose will be measured every five minutes for the first approximately 2.5 hours, and thereafter every 10-15 minutes. During the glucose-clamp study day the infusion rate of glucose will be adjusted continuously to match the glucose levels measured on the glucagon study day.
Blood samples for the analysis of plasma glucagon, insulin, C-peptide etc. will be drawn every five minutes for the first 60 minutes, and thereafter every 15-30 minutes.
After approximately three hours cognitive testing will be performed. After four hours, the infusion of either glucagon or glucose will be terminated. The final blood samples will be drawn 15 and 30 minutes after termination of the infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucagon infusion followed by glucose-clamp | Experimental | The first study day is a 240 minutes infusion of glucagon (10ng/kg/min). The second study day is a 240 minutes infusion of glucose (20% w/v). The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucagon Infusion | Other | A 240 minutes infusion of glucagon (10 ng/kg/min) |
|
| Measure | Description | Time Frame |
|---|---|---|
| C-peptide (0-90 minutes) | Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-90 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| C-peptide to glucose ratio (0-90 minutes) | Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-90 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| Word recall cognitive test | Difference in the word recall cognitive test between the glucagon infusion study day and the glucose clamp study day | During intervention (180-240 minutes) |
| Three-letter recall cognitive test |
Inclusion Criteria:
Exclusion Criteria:
Enrolment in other research projects that might interfere with the study
Diabetes diagnosis (type 1 and 2)
Pregnancy or breastfeeding
Use of medications which, in the opinion of the investigator, may jeopardise participant's safety or compliance with the protocol
Diagnosis of psychiatric disorders, dementias, or any other neurological disorders that in the opinion of the investigator precludes compliance with the study protocol, evaluation of the results or represents an unacceptable risk for the participants safety
Severe claustrophobia
Impaired liver function defined as either alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) ≥ 2 times normal values
Kidney disease defined as serum creatinine levels ≥ 126 μmol/L for male and ≥ 111 μmol/L for female
Cardiac problems including any of the following:
Inadequately treated blood pressure at screening defined as repeated resting blood pressure outside the range 90-150 mmHg for systolic and 50-100 mmHg for diastolic
Active or recent malignant disease
Inability to perform neuropsychological tests judged by the investigator (e.g. visual or auditory impairment or language barriers)
Current or history of severe alcohol use or drug/chemical abuse as per investigator's judgement
Any chronic disorders or severe diseases which, in the opinion of the investigator, might jeopardise participant's safety or compliance with the protocol
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| Name | Affiliation | Role |
|---|---|---|
| Nicolai J Wewer Albrecthsen, MD PhD | Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark | Copenhagen | 2400 | Denmark |
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| ID | Term |
|---|---|
| D015309 | Glucose Clamp Technique |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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| Glucose clamp | Other | A 240 minutes infusion of 20 % w/v glucose. The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day. |
|
| C-peptide to glucose ratio (0-240 minutes) |
Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day |
| During intervention (0-240 minutes) |
| C-peptide (0-240 minutes) | Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| C-peptide (0 minutes-glucose peak) | Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-time to plasma glucose peak concentration (assessed up to two hours)) |
| C-peptide deconvolution (0-240 minutes) | Difference in deconvolution of plasma concentrations of C-peptide between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| Insulin (0-90 minutes) | Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-90 minutes) |
| Insulin (0-240 minutes) | Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| Time to glucagon peak | Time to glucagon peak on the glucagon study day | During intervention (0-240 minutes) |
| Time to glucagon steady state | Time to glucagon steady state on the glucagon study day | During intervention (0-240 minutes) |
| Glucagon concentration at steady state | Plasma glucagon steady state concentration on the glucagon infusion study day | During intervention (0-240 minutes) |
| Glucose (0-90 minutes) | Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-90 minutes) |
| Glucose (0-240 minutes) | Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| Glucose peak | Difference in plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| Time to glucose peak | Difference in time to plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day | During intervention (0-time to plasma glucose peak concentration (assessed up to two hours) |
| Glucose infused | Glucose (g) infused on the glucose clamp study day | During intervention (0-240 minutes) |
| cAMP (0-90 minutes) | Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-90 minutes) |
| cAMP (0-240 minutes) | Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| cAMP (240-300 minutes) | Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (240-300 minutes) |
| Cognitive function | Difference in cognitive function assessed as a composite score from the cognitive testing (SCIP testing) between the glucagon infusion study day and the glucose clamp study day | During intervention (180-240 minutes) |
Difference in the three-letter recall cognitive test between the glucagon infusion study day and the glucose clamp study day
| During intervention (180-240 minutes) |
| Verbal fluency cognitive test | Difference in the verbal fluency cognitive test between the glucagon infusion study day and the glucose clamp study day | During intervention (180-240 minutes) |
| Delayed word recall cognitive test | Difference in the delayed word recall cognitive test between the glucagon infusion study day and the glucose clamp study day | During intervention (180-240 minutes) |
| Visuomotor cognitive test | Difference in the visuomotor cognitive test between the glucagon infusion study day and the glucose clamp study day | During intervention (180-240 minutes) |
| Triglycerides (0-240 minutes) | Difference in plasma concentration of triglycerides assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day | During intervention (0-240 minutes) |
| D003933 | Diagnosis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |