Incretin EffectNCT00529048
Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes
An observational study of Incretin Effect, run by Herlev Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Incretin Effect
- What is being tested?
- Oral Glucose Tolerance Test, Isoglycemic clamp and Gastric emptying rate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 16 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2007to Sep 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
- Caucasians
Show all 10Show fewer
- Normal oral glucose tolerance according to WHO's criteria
- Normal Hemoglobin
- Agree to participate (orally and in writing)
- BMI: 23-35 kg/m2
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Endokrinologisk afd. J, Herlev Hospital
Herlev, Capital Region, 2730
About this study
Official title: Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges
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.
Read the 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.
- Conditions
- Incretin Effect
- Being tested
- Oral Glucose Tolerance Test, Isoglycemic clamp, Gastric emptying rate
- Keywords
- Type 2 diabetes mellitus, Incretin effect, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Isoglycemic clampOther
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Gastric emptying rateOther
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve
| Study group | Role | What they receive |
|---|---|---|
| T2DM | T2DM patients (WHO-criteria) Receives: Other: Oral Glucose Tolerance Test; Other: Isoglycemic clamp; Other: Gastric emptying rate | |
| CTRL | Healthy control subjects matched individually to the cases. Receives: Other: Oral Glucose Tolerance Test; Other: Isoglycemic clamp; Other: Gastric emptying rate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress in Incretin effect in patients with T2DM compared with healthy subjects
Measured: 4 hours
Secondary outcomes (1)
GIP and GLP-1 responscurvs
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2007 (estimated)
- Study startOct 2007
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Incretin EffectStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen, Merck Sharp & Dohme LLC, Forskningsrådet, Diabetesforeningen
- Investigators
- Tina Villsbøll, MD.DMSc., Study chair, Herlev HospitalFilip K Knop, MD.Phd., Study director, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00529048
- Sponsor's protocol ID
- INK-GLUKOSE1
- Status last verified
- Oct 2009
- First submitted
- 12 Sep 2007
- Last updated
- 20 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.2337/diab.44.1.16.
PubMed 7813808Tseng 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.
PubMed 10362617Wang 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.
PubMed 7814643Habener JF. The incretin notion and its relevance to diabetes. Endocrinol Metab Clin North Am. 1993 Dec;22(4):775-94.
PubMed 8125072Edwards 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.
PubMed 9892226Gault 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.
PubMed 12627321Miyawaki 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.
PubMed 10611300Scrocchi 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.
PubMed 8898756Nauck 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.
PubMed 3514343Vilsboll 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.
PubMed 12189441Kjems 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.
PubMed 12540611Nauck 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.
PubMed 3522621Vilsboll 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.
PubMed 12832099Bagger 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.
PubMed 24879388Bagger 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.
PubMed 21252240
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges
- ClinicalTrials.gov ID
- NCT00529048
- Acronym / sponsor ID
- INK-GLUKOSE1
- Conditions
- Incretin Effect
- Keywords
- Type 2 diabetes mellitus, Incretin effect, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- University of Copenhagen, Merck Sharp & Dohme LLC, Forskningsrådet, Diabetesforeningen
- Study start
- Oct 2007
- Study completion
- Sep 2009 (actual)
- First posted
- 14 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T2DM | – | Other: Oral Glucose Tolerance Test, Other: Isoglycemic clamp, Other: Gastric emptying rateT2DM patients (WHO-criteria) |
| CTRL | – | Other: Oral Glucose Tolerance Test, Other: Isoglycemic clamp, Other: Gastric emptying rateHealthy control subjects matched individually to the cases. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Glucose Tolerance TestThe test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water. | Other | CTRL, T2DM |
| Isoglycemic clampI.v. glucose infusion initiating the glucose responds curves from the OGTT | Other | CTRL, T2DM |
| Gastric emptying rateParacetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve | Other | CTRL, T2DM |
Primary outcome
Progress in Incretin effect in patients with T2DM compared with healthy subjects
Time frame: 4 hours
1 secondary outcome
GIP and GLP-1 responscurvs
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2009.
- Background: PubMed 7813808Kolligs 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.
- Background: PubMed 10362617Tseng 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.
- Background: PubMed 7814643Wang 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.
- Background: PubMed 8125072Habener JF. The incretin notion and its relevance to diabetes. Endocrinol Metab Clin North Am. 1993 Dec;22(4):775-94.
- Background: PubMed 9892226Edwards 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.
- Background: PubMed 12627321Gault 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.
- Background: PubMed 10611300Miyawaki 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.
- Background: PubMed 8898756Scrocchi 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.
- Background: PubMed 3514343Nauck 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.
- Background: PubMed 12189441Vilsboll 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.
- Background: PubMed 12540611Kjems 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.
- Background: PubMed 3522621Nauck 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tina Villsbøll, MD.DMSc. study chair
Herlev Hospital
Filip K Knop, MD.Phd. study director
Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Incretin Effect, run by Herlev Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress in Incretin effect in patients with T2DM compared with healthy subjects (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00529048, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2009.