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

NCT01507597 | Completed

• 2 other identifiers: GlukaStaseH-3-2011-088
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Plasma Glucagon response to the GLP-1 infusion / glucose clamp

  The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

• Plasma GLP-1 response to the GLP-1 infusion / glucose clamp

  The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

• Plasma Glucose response to the GLP-1 infusion / glucose clamp

  The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

Secondary Outcomes (5)

• Resting Metabolic Rate response to the GLP-1 infusion / glucose clamp

  at 0, 120, and 180 min

• Hunger scores response to the GLP-1 infusion / glucose clamp

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

• plasma Insulin response to the GLP-1 infusion / glucose clamp

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

• plasma GIP response to the GLP-1 infusion / glucose clamp

  At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min

• Food Intake

  at 210 min

Study Arms (3)

Healthy Subjects

OTHER

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36)); Drug: NaCl

T2DM

OTHER

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36)); Drug: NaCl

T1DM

OTHER

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36)); Drug: NaCl

Interventions

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

Healthy Subjects; T1DM; T2DM

NaCl 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)

Healthy Subjects; T1DM; T2DM

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Gentofte University Hospital

Hellerup, DK-2900, Denmark

Location

Related Publications (1)

• 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.

  PMID: 33722838 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1

Interventions

glucagon-like peptide 1 (7-36)

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 13, 2011
• First Posted: January 11, 2012
• Study Start: December 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

DK (1)