Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes
NCT ID: NCT00529048
Last Updated: 2009-10-20
Study Results
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Basic Information
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COMPLETED
16 participants
OBSERVATIONAL
2007-10-31
2009-09-30
Brief Summary
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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.
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Detailed Description
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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 and corresponding isoglycemic iv glucose challenges. The proposed studies will answer important questions on the pathophysiology underlying T2DM and be of importance in relation to future preventive- and treatment strategies.
Eight patients with T2DM and 8 matched healthy subjects will be evaluated with oral glucose tolerance tests (OGTT) using increasing glucose loads (25, 50 and 100 g glucose) and isoglycemic iv glucose tolerance tests imitating the glucose concentrations as obtained during the oral glucose loads. The results will describe the regulation of the incretin effect in patients with T2DM and, thereby, contribute to the clarification of the pathophysiology of the postprandial hyperglycemia characterizing these patients.
Conditions
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Study Design
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CASE_CONTROL
CROSS_SECTIONAL
Study Groups
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T2DM
T2DM patients (WHO-criteria)
Oral Glucose Tolerance Test
The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.
Isoglycemic clamp
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Gastric emptying rate
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve
CTRL
Healthy control subjects matched individually to the cases.
Oral Glucose Tolerance Test
The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.
Isoglycemic clamp
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Gastric emptying rate
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve
Interventions
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Oral Glucose Tolerance Test
The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.
Isoglycemic clamp
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Gastric emptying rate
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve
Eligibility Criteria
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Inclusion Criteria
* Normal Hemoglobin
* Agree to participate (orally and in writing)
* HbA1c: 6.5-9 %
* BMI: 23-35 kg/m2
* Caucasians
* Normal oral glucose tolerance according to WHO's criteria
* Normal Hemoglobin
* Agree to participate (orally and in writing)
* BMI: 23-35 kg/m2
Exclusion Criteria
* 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
* 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
* Medical treatment witch cannot be stopped for 12 hours
* Pregnancy or breastfeed
18 Years
ALL
Yes
Sponsors
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University of Copenhagen
OTHER
Merck Sharp & Dohme LLC
INDUSTRY
Forskningsrådet
UNKNOWN
Diabetesforeningen
OTHER
Herlev Hospital
OTHER
Responsible Party
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University of Copehagen
Principal Investigators
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Tina Villsbøll, MD.DMSc.
Role: STUDY_CHAIR
Herlev Hospital
Filip K Knop, MD.Phd.
Role: STUDY_DIRECTOR
Herlev Hospital
Locations
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Endokrinologisk afd. J, Herlev Hospital
Herlev, Capital Region, Denmark
Countries
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References
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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.
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.
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.
Habener JF. The incretin notion and its relevance to diabetes. Endocrinol Metab Clin North Am. 1993 Dec;22(4):775-94.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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INK-GLUKOSE1
Identifier Type: -
Identifier Source: org_study_id
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