NCT00716170

Brief Summary

In order to investigate the mechanisms underlying the hyperglucagonemia characterizing patients with type 2 diabetes mellitus (T2DM) we wish to test the following hypothesis: Do pancreatic alpha-cells exhibit inappropriate glucagon responses to substances released from the small intestine (GIP, GLP-2 and GLP-2) in patients with T2DM?

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jul 2008

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2008

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

July 10, 2008

Completed
6 days until next milestone

First Posted

Study publicly available on registry

July 16, 2008

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2009

Completed
Last Updated

November 28, 2013

Status Verified

April 1, 2009

Enrollment Period

1 year

First QC Date

July 10, 2008

Last Update Submit

November 27, 2013

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes MellitusGlucagonInsulinIncretin hormonesGlucose-dependent insulinotropic polypeptideGlucagon-like peptide-1Glucagon-like peptide-2

Outcome Measures

Primary Outcomes (1)

  • Plasma glucagon responses

    3 hours

Study Arms (1)

A:

Patients with type 2 diabetes mellitus

Biological: Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)

Interventions

Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)BIOLOGICAL

Day A: Oral glucose tolerance test (50g glucose) Day B: Isoglycemic intravenous (iv) glucose infusion Day C: Isoglycemic iv glucose infusion + iv GIP infusion (0-20 min: 4 pmol/kg body weight/min; 20-50 min: 2 pmol/kg body weight/min) Day D: Isoglycemic iv glucose infusion + iv GLP-1 infusion (0-20 min: 0,6 pmol/kg body weight/min; 20-50 min: 0,3 pmol/kg body weight/min) Day E: Isoglycemic iv glucose infusion + iv GLP-2 infusion (0-20 min: 1 pmol/kg body weight/min; 20-50 min: 0,5 pmol/kg body wight/min) Day F: Isoglycemic iv glucose infusion + iv infusion of GIP, GLP-1 and GLP-2 in doses as Day C, D and E.

Also known as: Human GIP (glucose-dependent insulinotropic polypeptide), Human GLP-1 (glucagon-like peptide-1), Human GLP-2 (glucagon-like peptide-2)
A:

Eligibility Criteria

Age35 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The patients will be recruted from the outpatient clinic of Department of Endocrinology, Herlev Hospital.

You may qualify if:

  • Caucasians with diet and/or tablet treated T2DM of at least 3 months duration (diagnosed according to the criterias of the World Health Organization (WHO))
  • Normal Hemoglobin
  • Prior Informed Consent

You may not qualify if:

  • Liver disease (ALAT/ASAT \> 2 x upper normal value)
  • Diabetic nephropathy (se-creatinin \> 130 um and/or albuminuria
  • Treatment with drugs that cannot be discontinued for 12 hours

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Endocrinology J, Herlev Hospital

Herlev, Herlev, 2730, Denmark

Location

Related Publications (15)

  • Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003 Jan;26 Suppl 1:S5-20. doi: 10.2337/diacare.26.2007.s5. No abstract available.

    PMID: 12502614BACKGROUND

  • Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (first two parts). N Engl J Med. 1981 Jun 18;304(25):1518-24. doi: 10.1056/NEJM198106183042504. No abstract available.

    PMID: 7015132BACKGROUND

  • Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (second of two parts). N Engl J Med. 1981 Jun 25;304(26):1575-80. doi: 10.1056/NEJM198106253042604. No abstract available.

    PMID: 7015135BACKGROUND

  • Shah P, Vella A, Basu A, Basu R, Schwenk WF, Rizza RA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2000 Nov;85(11):4053-9. doi: 10.1210/jcem.85.11.6993.

    PMID: 11095432BACKGROUND

  • Knop FK, Vilsboll T, Madsbad S, Holst JJ, Krarup T. Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus. Diabetologia. 2007 Apr;50(4):797-805. doi: 10.1007/s00125-006-0566-z. Epub 2007 Jan 16.

    PMID: 17225124BACKGROUND

  • Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab. 1986 Aug;63(2):492-8. doi: 10.1210/jcem-63-2-492.

    PMID: 3522621BACKGROUND

  • Knop FK, Vilsboll T, Hojberg PV, Larsen S, Madsbad S, Volund A, Holst JJ, Krarup T. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes. 2007 Aug;56(8):1951-9. doi: 10.2337/db07-0100. Epub 2007 May 18.

    PMID: 17513701BACKGROUND

  • Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993 Aug;36(8):741-4. doi: 10.1007/BF00401145.

    PMID: 8405741BACKGROUND

  • Holst JJ. On the physiology of GIP and GLP-1. Horm Metab Res. 2004 Nov-Dec;36(11-12):747-54. doi: 10.1055/s-2004-826158.

    PMID: 15655703BACKGROUND

  • Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, Schmidt WE, Nauck MA. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003 Jun;46(6):798-801. doi: 10.1007/s00125-003-1103-y. Epub 2003 May 23.

    PMID: 12764578BACKGROUND

  • Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186.

    PMID: 8423228BACKGROUND

  • Vilsboll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia. 2002 Aug;45(8):1111-9. doi: 10.1007/s00125-002-0878-6. Epub 2002 Jul 4.

    PMID: 12189441BACKGROUND

  • Meier JJ, Nauck MA, Pott A, Heinze K, Goetze O, Bulut K, Schmidt WE, Gallwitz B, Holst JJ. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology. 2006 Jan;130(1):44-54. doi: 10.1053/j.gastro.2005.10.004.

    PMID: 16401467BACKGROUND

  • Schmidt WE, Siegel EG, Creutzfeldt W. Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia. 1985 Sep;28(9):704-7. doi: 10.1007/BF00291980.

    PMID: 3905480BACKGROUND

  • Sorensen LB, Flint A, Raben A, Hartmann B, Holst JJ, Astrup A. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int J Obes Relat Metab Disord. 2003 Apr;27(4):450-6. doi: 10.1038/sj.ijo.0802247.

    PMID: 12664078BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood plasma and leucocytes

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes MellitusInsulin Resistance

Interventions

IncretinsGlucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinism

Intervention Hierarchy (Ancestors)

HormonesHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesGlucagon-Like PeptidesProglucagonGastrointestinal Hormones

Study Officials

  • Tina Vilsbøll, MD DMSc

    Herlev Hospital

    STUDY CHAIR

  • Filip K Knop, MD PhD

    Gentofte Hospital

    STUDY DIRECTOR

Study Design

Study Type
observational
Observational Model
CASE ONLY
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

July 10, 2008

First Posted

July 16, 2008

Study Start

July 1, 2008

Primary Completion

July 1, 2009

Study Completion

July 1, 2009

Last Updated

November 28, 2013

Record last verified: 2009-04

Locations

DK(1)