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

Not Applicable

Completed

• Conditions: Metabolic Syndrome; Diabetes
• Interventions: Drug: Intravenous glucagon; Drug: Intravenous saline

• Registration Number: NCT03061227
• Lead Sponsor: University Hospital Tuebingen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-02-09
• Study Start: 2017-02-10
• Study First Submitted QC: 2017-02-17
• Study First Posted: 2017-02-23
• Primary Completion: 2019-01-17
• Status Verified: 2020-04
• Study Completion: 2020-04-30
• Last Update Submitted: 2020-05-04
• Last Update Posted: 2020-05-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Intravenous glucagon	Intravenous glucagon	Low-dose glucagon infusion (0.5 pmol/min/kg body weight) over 150 minutes during a standardized 75 g oral glucose tolerance test
Intravenous saline	Intravenous saline	Saline infusion over 150 minutes during a standardized 75 g oral glucose tolerance test

Primary Outcome Measures

Name	Time	Method
Brain activity	change from baseline to 120 minutes after oral glucose challenge	Resting-state brain activity assessed by fMRI

Secondary Outcome Measures

Name	Time	Method
Hunger rating	before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion	On visual analogue scale
Glucose tolerance	0-120 minutes	Assessed by 75 g oral glucose tolerance test
Insulin sensitivity	0-120 minutes	Assessed during 75 g oral glucose tolerance test
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.
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)

Trial Locations

Locations (1)

University Hospital Tübingen; 🇩🇪 Tübingen, Germany