The Effect of GLP-1 on the Inhibition of Glucagon Secretion

NCT ID: NCT01507597

Last Updated: 2013-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-08-31

Brief Summary

Diabetes(both types) are recognized by high levels of glucagon in the circulation.

Glucagon is known to increase blood glucose, and might therefore contribute to the respective diseases. Under some circumstances the gut hormone GLP-1 inhibits the glucagon secretion.

The investigators aim to identify the impact of GLP-1 on the glucagon secretion, at increasing blood glucose levels in healthy subjects, in patients with type 2 diabetes, and in patients with type 1 diabetes.

The investigators think that the effect of GLP-1 on the glucagon secretion might be dependent of blood glucose levels.

Conditions

Type 2 Diabetes; Type 1 Diabetes

Keywords

Glucagon-like peptide-1; Glucagon; Normal physiology; T2DM; T1DM

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Healthy Subjects

Group Type: OTHER

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

NaCl

Intervention Type: DRUG

Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

T2DM

Group Type: OTHER

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

NaCl

Intervention Type: DRUG

Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

T1DM

Group Type: OTHER

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

NaCl

Intervention Type: DRUG

Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Intervention Type: DRUG

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Interventions

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Intervention Type: DRUG

NaCl

Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Intervention Type: DRUG

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Intervention Type: DRUG

Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients with T2DM

• Above the age of 35 years, treatment with diet or oral anti-diabetic medication. Diagnosed with T2DM in at leat three months in advance(WHO criterion)
• Normal hemoglobin
• Informed content Patients with T1DM
• T1DM (WHO criterion)
• Plasma-C-peptid negative due to arginin-test
• Normal hemoglobin
• age> 18 years
• Informed content Healthy subjects
• Normal fasting plasma glucose and normal glucose tolerance (WHO criterion)
• Normal hemoglobin
• Age >18 years
• Informed content

Exclusion Criteria

Patients with T2DM

• Treatment with glitazones and/or gliptins
• Inflammatory bowels disease
• previous bowel resection with or without stomy
• Nephropathy (serum creatinin >150 µM and/or albuminuria)
• Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
• Medical treatment impossible to break for 12h.
• Age >80 years Patients with T1DM
• Overweight (BMI >30 kg/m2)
• Inflammatory bowels disease
• previous bowel resection with or without stomy
• Nephropathy (serum creatinin >150 µM and/or albuminuria)
• Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
• Medical treatment impossible to break for 12h (except treatment with insulin).
• Age >80 years

Healthy subjects

• Diabetes
• Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)
• First order relatives with diabetes
• Overweight (BMI >30 kg/m2)
• Inflammatory bowels disease
• previous bowel resection with or without stomy
• Nephropathy (serum creatinin >150 µM and/or albuminuria)
• Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
• Medical treatment impossible to break for 12h.
• Age >80 years

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Jonatan I Bagger

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Gentofte University Hospital

Hellerup, , Denmark

Countries

Denmark

References

Bagger JI, Grondahl MFG, Lund A, Holst JJ, Vilsboll T, Knop FK. Glucagonostatic Potency of GLP-1 in Patients With Type 2 Diabetes, Patients With Type 1 Diabetes, and Healthy Control Subjects. Diabetes. 2021 Jun;70(6):1347-1356. doi: 10.2337/db20-0998. Epub 2021 Mar 15.

Reference Type: DERIVED

PMID: 33722838 (View on PubMed)

Other Identifiers

H-3-2011-088

Identifier Type: OTHER

Identifier Source: secondary_id

GlukaStase

Identifier Type: -

Identifier Source: org_study_id