Incretin Physiology and Beta-Cell Function Before and After Remission of Type 2 Diabetes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by Glostrup University Hospital, Copenhagen.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Copenhagen
European Foundation for the Study of Diabetes
Novo Nordisk A/S
Desirée og Niels Ydes Fond
Information provided by:
Glostrup University Hospital, Copenhagen
ClinicalTrials.gov Identifier:
NCT00625040
First received: February 19, 2008
Last updated: March 7, 2008
Last verified: March 2008
  Purpose

To evaluate the impact of laparoscopic adjustable gastric banding (LAGB) on beta-cell function, insulin sensitivity, incretin function, postprandial secretion of incretin hormones (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) in morbidly obese patients and to describe the pathophysiological mechanisms involved in the amelioration of glucose homeostasis during long-term weight loss.


Condition Intervention
Type 2 Diabetes Mellitus
Obesity
Other: Oral glucose tolerance test (OGTT), isoglycemic iv. clamp, liquid meal test, gastric emptying rate

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Incretin Physiology and Beta-Cell Function Before and After Remission of Type 2 Diabetes - Effects of Long-Term Weight Loss Following Laparoscopic Adjustable Gastric Banding

Resource links provided by NLM:


Further study details as provided by Glostrup University Hospital, Copenhagen:

Primary Outcome Measures:
  • Incretin effect before and one year after gastric banding in obese patients with type 2 diabetes compared with obese patients without diabetes [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • GLP-1 and GIP response curves [ Time Frame: One year ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

p-glucose, p-glucagon, p-GLP1, p-GIP, p-cpeptid, p-insulin, p-paracetamol, buffy coat, urine, whole blood sampels


Estimated Enrollment: 20
Study Start Date: January 2008
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
A
Obese patients with type 2 diabetes mellitus (WHO criteria) with a Body Mass Index >37 kg/m2
Other: Oral glucose tolerance test (OGTT), isoglycemic iv. clamp, liquid meal test, gastric emptying rate

OGTT: The test is performed with 50 g of glucose deluded in 300 ml water.

Isoglycemic iv. clamp: Iv. glucose infusion mimicking the glucose response curves from the OGTT.

Liquid Meal test: The test is performed with 100g of artificial breast milk deluded in 300 ml. water.

Gastric Emptying Rate: Paracetamol absorption test.

B
Obese patients without diabetes with a Body Mass Index >37 kg/m2
Other: Oral glucose tolerance test (OGTT), isoglycemic iv. clamp, liquid meal test, gastric emptying rate

OGTT: The test is performed with 50 g of glucose deluded in 300 ml water.

Isoglycemic iv. clamp: Iv. glucose infusion mimicking the glucose response curves from the OGTT.

Liquid Meal test: The test is performed with 100g of artificial breast milk deluded in 300 ml. water.

Gastric Emptying Rate: Paracetamol absorption test.


Detailed Description:

Morbid obesity represents a serious health issue in Western countries, with a rising incidence and a strong association with increased mortality and serious co-morbidities, such as diabetes. Type 2 diabetes is associated with a significantly higher risk of micro- and macro vascular complications. The pathogenesis of type 2 diabetes is not jet established. In patients with type 2 diabetes the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs.

Surgical interventions, such as laparoscopic gastric banding have been developed with the aim of providing a laparoscopic placed device that is safe and effective in generating substantial weight loss. Investigations have proved that substantial weight loss in patients with type 2 diabetes is associated with an improved energy homeostasis and improved insulin secretion. It has also been proved that about 60% of patients with type 2 diabetes undergoing surgical intervention with gastric banding return to a normal glucose homeostasis.

This project concerns the pathogenesis of these amazing results. By investigation of the incretin effect, the secretion of GIP and GLP-1, the insulinresponse and -sensitivity and the beta-cell responsiveness to glucose in 10 obese patients with and 10 patients without type 2 diabetes before and after laparoscopic gastric banding the aim of this project is to establish whether the reduced incretin effect in patients with type 2 diabetes is a primary event leading to the disease, or a consequence of the diabetic state.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The cases and controls are recruited from The Bariatric Clinic at Glostrup Hospital

Criteria

Inclusion Criteria: (cases)

  • Caucasians with type 2 diabetes mellitus according to WHO's criteria
  • Patients fulfilling the criteria for laparoscopic gastric banding
  • Normal Hemoglobin
  • Informed consent

Inclusion Criteria: (controls)

  • Caucasians without type 2 diabetes mellitus
  • Normal OGTT (75 g of glucose) according to WHO's criteria
  • Patients fulfilling the criteria for laparoscopic gastric banding
  • Normal Hemoglobin
  • Informed consent

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 wich cannot be stopped for 12 hours
  • Treatment with insulin, GLP-1 analogues or DPP-4 inhibitors

Exclusion Criteria: (controls)

  • Liver disease (ALAT > 2 x normal level)
  • Nephropathy (s-creatinin > 130 µM or albuminuria)
  • Relatives (parents/siblings) with T2DM
  • Medical treatment witch cannot be stopped for 12 hours
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625040

Contacts
Contact: Katrine Bagge Hansen, MD +4540509942 kbaggehansen@dadlnet.dk
Contact: Steen Larsen, MD DMSc +4543232805/04 stla@glo.regionh.dk

Locations
Denmark
Glostrup Hospital Recruiting
Glostrup, Denmark, 2600
Contact: Katrine Bagge Hansen, MD    +4540509942    kbaggehansen@dadlnet.dk   
Contact: Steen Larsen, MD, DMSc    +4543232805/04    stla@glo.region   
Principal Investigator: Katrine Bagge Hansen, MD         
Sponsors and Collaborators
Glostrup University Hospital, Copenhagen
University of Copenhagen
European Foundation for the Study of Diabetes
Novo Nordisk A/S
Desirée og Niels Ydes Fond
Investigators
Principal Investigator: Katrine Bagge Hansen, MD Glostrup Hospital
Study Director: Filip K Knop, MD, PhD Gentofte Hospital
Study Director: Steen Larsen, MD, DMSc Glostrup Hospital
Study Director: Jens Juul Holst, MD,DMSc University of Copenhagen
Study Chair: Viggo Kristensen, MD Glostrup Hospital
  More Information

No publications provided

Responsible Party: Katrine Bagge Hansen, MD, Glostrup Hospital
ClinicalTrials.gov Identifier: NCT00625040     History of Changes
Other Study ID Numbers: GB-INK
Study First Received: February 19, 2008
Last Updated: March 7, 2008
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by Glostrup University Hospital, Copenhagen:
Incretin effect
Gastric banding
Glucagon
Glucagon-Like Peptide 1
Gastric Inhibitory Peptide
Glucose Intestinal Peptide
Insulin
C-peptide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014