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

Metabolic and Central Nervous System Characterisation of the Phenotype of Non-suppressed (Rising) Glucagon After Glucose Challenge

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 Overview

• Status: Completed
• Conditions: Diabetes; Metabolic Syndrome
• Intervention / Treatment: Drug: Intravenous glucagon; Drug: Intravenous saline

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University Hospital Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: Intravenous glucagon; Randomized application of glucagon or saline during oral glucose tolerance test
Placebo Comparator: Intravenous saline; Saline infusion over 150 minutes during a standardized 75 g oral glucose tolerance test	Drug: Intravenous saline; Randomized application of glucagon or saline during oral glucose tolerance test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain activity	Resting-state brain activity assessed by fMRI	change from baseline to 120 minutes after oral glucose challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hunger rating	On visual analogue scale	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)	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	0-120 minutes
Insulin sensitivity	Assessed during 75 g oral glucose tolerance test	0-120 minutes
Basal energy expenditure	Assessed by indirect calorimetry	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.	0-150 minutes

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Actual): January 17, 2019
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): May 5, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: 529_2016BO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No