Metabolic Syndrome, Diabetes
Conditions
Brief summary
The investigators previously characterized a phenotype with non-suppressed glucagon at 120 minutes after standardized oral glucose load. This phenotype is associated with healthy metabolic traits such as lower BMI, higher insulin sensitivity and lower liver fat content. Glucagon is a pleiotropic hormone that, besides its main action on increasing endogenous glucose production, also reduces appetite and increases basal energy expenditure. The aims of this study are to i. detect functional differences in the appetite-related central nervous system (CNS) areas between the suppressed and non-suppressed glucagon phenotype ii. mimick the non-suppressed glucagon phenotype in those participants who suppress glucagon by administering a very-low-dose glucagon infusion and retest them.
Interventions
DRUGIntravenous glucagon
Randomized application of glucagon or saline during oral glucose tolerance test
Randomized application of glucagon or saline during oral glucose tolerance test
Sponsors
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 18.5- 29.9 kg/m2 * written informed consent
Exclusion criteria
* Current 1. febrile infection with temperatures\> 38.5 ° C in the last 14 days 2. Blood donation within the last 12 weeks Pre-study Inclusion * Chronic diseases: 1. Diabetes mellitus 2. Known liver diseases (hepatitisB/C, hemochromatosis, NASH) 3. Chronic inflammatory diseases (rheumatoid arthritis, Crohn's disease, ulcerative colitis) chronic renal insufficiency 4. Cancer (known malignant disease) 5. psychiatric diagnoses (bipolar disorder, schizophrenia, psychoses, depression, agoraphobia) 6. Persons with non-removable metal parts, e.g: * pacemaker * artificial heart valves * metal prostheses * implanted magnetic metal parts (screws, plates of operations) * spiral * metal slivers / garnet splinters * fixed braces * Acupuncture needle * Insulin pump * totally implantable venous access device (port) * tattoos, metallic eye shadows 7. Persons with impaired sensitivity and / or increased sensitivity to heating of the body 8. Medical history of venous thromboembolism 9. alcohol consumption of more than 50g / day 10. In physical examination: blood pressure \> 160/100 mmHg pathologic cardiac murmurs (diastolic or systolic louder than 2/6) 11. in the blood test: fasting glucose ≥ 125 mg/dl or HbA1c ≥ 6.5% AST or ALT\> 2.5x upper limit of the reference range (\> 125 U/l) Hb \<12 g/dl C reactive protein (CRP) \> 5 mg / dL or leukocytes\> 15000/μl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain activity | change from baseline to 120 minutes after oral glucose challenge | Resting-state brain activity assessed by fMRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain response to food cues | before, 30 minutes and 120 minutes after oral glucose challenge and start of glucagon/saline infusion | Assessed by functional magnetic resonance imaging (fMRI) |
| Glucose tolerance | 0-120 minutes | Assessed by 75 g oral glucose tolerance test |
| Hunger rating | before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion | On visual analogue scale |
| Basal energy expenditure | 150 minutes after oral glucose challenge | Assessed by indirect calorimetry |
| Change in hormone levels | 0-150 minutes | Change in adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), fibroblast growth factor 21(FGF-21) after oral glucose challenge and start of glucagon/saline infusion. |
| Insulin sensitivity | 0-120 minutes | Assessed during 75 g oral glucose tolerance test |
Countries
Germany
Outcome results
None listed