Characterization of Metabolic and Brain Effects of Rising Glucagon During an Oral Glucose Challenge

University Hospital Tuebingen32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Metabolic Syndrome Diabetes

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Brain activity

Resting-state brain activity assessed by fMRI

Time frame: change from baseline to 120 minutes after oral glucose challenge

Secondary Outcomes

Hunger rating

On visual analogue scale

Time frame: before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion

Brain response to food cues

Assessed by functional magnetic resonance imaging (fMRI)

Time frame: before, 30 minutes and 120 minutes after oral glucose challenge and start of glucagon/saline infusion

Glucose tolerance

Assessed by 75 g oral glucose tolerance test

Time frame: 0-120 minutes

Insulin sensitivity

Assessed during 75 g oral glucose tolerance test

Time frame: 0-120 minutes

Basal energy expenditure

Assessed by indirect calorimetry

Time frame: 150 minutes after oral glucose challenge

Change in hormone levels

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.

Time frame: 0-150 minutes