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

University Hospital Tuebingen

Status: Completed

Conditions: Diabetes; Metabolic Syndrome

Treatments: Drug: Intravenous saline; Drug: Intravenous glucagon

Study type: Interventional

Funder types: Other

Identifiers

NCT03061227

529_2016BO1

Details and patient eligibility

About

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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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32 participants in 2 patient groups, including a placebo group

Intravenous glucagon

Active Comparator group

Description:

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

Treatment:

Drug: Intravenous glucagon

Intravenous saline

Placebo Comparator group

Description:

Saline infusion over 150 minutes during a standardized 75 g oral glucose tolerance test

Treatment:

Drug: Intravenous saline