Clinical trial NCT03061227: Characterization of Metabolic and Brain Effects of Rising Glucagon During an Oral Glucose Challenge
Official title: Metabolic and Central Nervous System Characterisation of the Phenotype of Non-suppressed (Rising) Glucagon After Glucose Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Diabetes
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Brain activity
timeFrame: change from baseline to 120 minutes after oral glucose challenge
Secondary outcomes:
measure: Hunger rating
timeFrame: before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion
measure: Brain response to food cues
timeFrame: before, 30 minutes and 120 minutes after oral glucose challenge and start of glucagon/saline infusion
measure: Glucose tolerance
timeFrame: 0-120 minutes
measure: Insulin sensitivity
timeFrame: 0-120 minutes
measure: Basal energy expenditure
timeFrame: 150 minutes after oral glucose challenge
measure: Change in hormone levels
timeFrame: 0-150 minutes
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: University Hospital Tübingen
Study officials:
References: