Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes - Full Text View

Purpose

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.

Condition	Intervention
Incretin Effect	Other: Oral Glucose Tolerance Test Other: Isoglycemic clamp Other: Gastric emptying rate

Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Dextrose

U.S. FDA Resources

Further study details as provided by Herlev Hospital:

Primary Outcome Measures:

Progress in Incretin effect in patients with T2DM compared with healthy subjects [ Time Frame: 4 hours ]

Secondary Outcome Measures:

GIP and GLP-1 responscurvs [ Time Frame: 4 hours ]

Biospecimen Retention: Samples With DNA

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

Enrollment:	16
Study Start Date:	October 2007
Study Completion Date:	September 2009

Groups/Cohorts	Assigned Interventions
T2DM T2DM patients (WHO-criteria)	Other: 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. Other: Isoglycemic clamp I.v. glucose infusion initiating the glucose responds curves from the OGTT Other: 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.	Other: 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. Other: Isoglycemic clamp I.v. glucose infusion initiating the glucose responds curves from the OGTT Other: Gastric emptying rate Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve

Detailed Description:

The impaired incretin effect in patients with type 2 diabetes mellitus (T2DM) has previously only been evaluated using a glucose load of 50 g, and it is uncertain whether patients with T2DM are capable of regulating their incretin effect equivalent to healthy subjects. Furthermore, it is of great interest to quantify the secretion of GIP and GLP-1 during increasing glucose loads in both patients with T2DM and in healthy subjects in order to evaluate whether an increased secretion of one or both of the two incretin hormones contributes to the regulation of the incretin effect.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-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.

Criteria

Inclusion Criteria: Cases

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

Exclusion Criteria:Cases

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

Inclusion Criteria: Control group

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: Control group

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00529048

Locations

Denmark
Endokrinologisk afd. J, Herlev Hospital
Herlev, Region Hovedstaden, Denmark, 2730

Sponsors and Collaborators

Herlev Hospital

University of Copenhagen

Merck

Forskningsrådet

Diabetesforeningen

Investigators

Study Chair:	Tina Villsbøll, MD.DMSc.	Herlev Hospital
Study Director:	Filip K Knop, MD.Phd.	Herlev Hospital

More Information

Publications:

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.

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 Pt 1):E1049-54.

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.

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

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.

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. 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.

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.

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.

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. 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.

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.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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

Responsible Party:	Jonatan Bagger, University of Copehagen
ClinicalTrials.gov Identifier:	NCT00529048 History of Changes
Other Study ID Numbers:	INK-GLUKOSE1
Study First Received:	September 12, 2007
Last Updated:	October 19, 2009
Health Authority:	Denmark: National Board of Health Denmark: The Danish National Committee on Biomedical Research Ethics Denmark: The Ministry of the Interior and Health

Keywords provided by Herlev Hospital:

Type 2 diabetes mellitus
Incretin effect
Glucagon-Like Peptide 1
Gastric Inhibitory Polypeptide

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Incretins

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013