NCT00529048

Brief Summary

Patients with T2DM lac a sufficient incretin response after oral glucose intake. It has only been tested using 50g of glucose. We don't know if patients with T2DM are capable of regulating the incretin effect like healthy people in responds to different amounts of glucose intake. The aim of the present study is to quantify the incretin effect in healthy subjects and in patients with T2DM during increasing amounts of oral glucose challenges. The proposed studies will answer important questions on the mechanisms underlying T2DM and be of importance in relation to future preventive- and treatment strategies.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
16

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Oct 2007

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

First Submitted

Initial submission to the registry

September 12, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 14, 2007

Completed
17 days until next milestone

Study Start

First participant enrolled

October 1, 2007

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
Last Updated

October 20, 2009

Status Verified

October 1, 2009

First QC Date

September 12, 2007

Last Update Submit

October 19, 2009

Conditions

Incretin Effect

Keywords

Type 2 diabetes mellitusIncretin effectGlucagon-Like Peptide 1Gastric Inhibitory Polypeptide

Outcome Measures

Primary Outcomes (1)

  • Progress in Incretin effect in patients with T2DM compared with healthy subjects

    4 hours

Secondary Outcomes (1)

  • GIP and GLP-1 responscurvs

    4 hours

Study Arms (2)

T2DM

T2DM patients (WHO-criteria)

Other: Oral Glucose Tolerance TestOther: Isoglycemic clampOther: Gastric emptying rate

CTRL

Healthy control subjects matched individually to the cases.

Other: Oral Glucose Tolerance TestOther: Isoglycemic clampOther: Gastric emptying rate

Interventions

Oral Glucose Tolerance TestOTHER

The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.

CTRLT2DM
Isoglycemic clampOTHER

I.v. glucose infusion initiating the glucose responds curves from the OGTT

CTRLT2DM
Gastric emptying rateOTHER

Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve

CTRLT2DM

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The Patients (Cases) will be recruted from the diabetes clinic at Depatment of Endocrinology at Herlev Hospital The control subjects will be recruted through the lokal papers, and individualy matched by age, sex and BMI to a patient befor enrollment.

You may qualify if:

  • Caucasians with T2DM according to WHO's criteria
  • Normal Hemoglobin
  • Agree to participate (orally and in writing)
  • HbA1c: 6.5-9 %
  • BMI: 23-35 kg/m2

You may not qualify if:

  • Liver disease (ALAT \> 2 x normal level)
  • Diabetic nephropathy (s-creatinin \> 130 µM or albuminuria)
  • Diabetic neuropathy (anamnestic)
  • Proliferative diabetic retinopathy (anamnestic)
  • Medical treatment witch cannot be stopped for 12 hours
  • Pregnancy or breastfeed
  • Treatment with Insulin or glitazones
  • Caucasians
  • Normal oral glucose tolerance according to WHO's criteria
  • Normal Hemoglobin
  • Agree to participate (orally and in writing)
  • BMI: 23-35 kg/m2
  • Liver disease (ALAT \> 2 x normal level)
  • Impaired function of the kidney (s-creatinin \> 130 µM or albuminuria)
  • Directly related til to someone suffering from diabetes mellitus
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Endokrinologisk afd. J, Herlev Hospital

Herlev, Capital Region, 2730, Denmark

Location

Related Publications (15)

  • Kolligs F, Fehmann HC, Goke R, Goke B. Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. Diabetes. 1995 Jan;44(1):16-9. doi: 10.2337/diab.44.1.16.

    PMID: 7813808BACKGROUND

  • Tseng CC, Zhang XY, Wolfe MM. Effect of GIP and GLP-1 antagonists on insulin release in the rat. Am J Physiol. 1999 Jun;276(6):E1049-54. doi: 10.1152/ajpendo.1999.276.6.E1049.

    PMID: 10362617BACKGROUND

  • Wang Z, Wang RM, Owji AA, Smith DM, Ghatei MA, Bloom SR. Glucagon-like peptide-1 is a physiological incretin in rat. J Clin Invest. 1995 Jan;95(1):417-21. doi: 10.1172/JCI117671.

    PMID: 7814643BACKGROUND

  • Habener JF. The incretin notion and its relevance to diabetes. Endocrinol Metab Clin North Am. 1993 Dec;22(4):775-94.

    PMID: 8125072BACKGROUND

  • Edwards CM, Todd JF, Mahmoudi M, Wang Z, Wang RM, Ghatei MA, Bloom SR. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes. 1999 Jan;48(1):86-93. doi: 10.2337/diabetes.48.1.86.

    PMID: 9892226BACKGROUND

  • Gault VA, O'Harte FP, Harriott P, Mooney MH, Green BD, Flatt PR. Effects of the novel (Pro3)GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin. Diabetologia. 2003 Feb;46(2):222-30. doi: 10.1007/s00125-002-1028-x. Epub 2003 Feb 12.

    PMID: 12627321BACKGROUND

  • Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, Kubota A, Fujimoto S, Kajikawa M, Kuroe A, Tsuda K, Hashimoto H, Yamashita T, Jomori T, Tashiro F, Miyazaki J, Seino Y. Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14843-7. doi: 10.1073/pnas.96.26.14843.

    PMID: 10611300BACKGROUND

  • Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, Drucker DJ. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med. 1996 Nov;2(11):1254-8. doi: 10.1038/nm1196-1254.

    PMID: 8898756BACKGROUND

  • Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.

    PMID: 3514343BACKGROUND

  • 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

  • Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003 Feb;52(2):380-6. doi: 10.2337/diabetes.52.2.380.

    PMID: 12540611BACKGROUND

  • 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

  • Vilsboll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept. 2003 Jul 15;114(2-3):115-21. doi: 10.1016/s0167-0115(03)00111-3.

    PMID: 12832099BACKGROUND

  • Bagger JI, Knop FK, Lund A, Holst JJ, Vilsboll T. Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals. Diabetologia. 2014 Aug;57(8):1720-5. doi: 10.1007/s00125-014-3264-2. Epub 2014 May 31.

    PMID: 24879388DERIVED

  • Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsboll T. Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 Mar;96(3):737-45. doi: 10.1210/jc.2010-2435. Epub 2011 Jan 20.

    PMID: 21252240DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

p-Glucose p-Glucagon p-insulin p-c-pep. p-GLP-1 p-GIP Buffy coat s-paracetamol

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical AnalysisClinical Chemistry TestsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, EndocrineInvestigative Techniques

Study Officials

  • Tina Villsbøll, MD.DMSc.

    Herlev Hospital

    STUDY CHAIR

  • Filip K Knop, MD.Phd.

    Herlev Hospital

    STUDY DIRECTOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 12, 2007

First Posted

September 14, 2007

Study Start

October 1, 2007

Study Completion

September 1, 2009

Last Updated

October 20, 2009

Record last verified: 2009-10

Locations

DK(1)