Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes

Completed

• Conditions: Incretin Effect
• Interventions: Other: Oral Glucose Tolerance Test; Other: Isoglycemic clamp; Other: Gastric emptying rate

• Registration Number: NCT00529048
• Lead Sponsor: Herlev Hospital

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.

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 Timeline

• Study First Submitted: 2007-09-12
• Study First Submitted QC: 2007-09-12
• Study First Posted: 2007-09-14
• Study Start: 2007-10
• Study Completion: 2009-09
• Status Verified: 2009-10
• Last Update Submitted: 2009-10-19
• Last Update Posted: 2009-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
T2DM	Isoglycemic clamp	T2DM patients (WHO-criteria)
T2DM	Oral Glucose Tolerance Test	T2DM patients (WHO-criteria)
T2DM	Gastric emptying rate	T2DM patients (WHO-criteria)
CTRL	Oral Glucose Tolerance Test	Healthy control subjects matched individually to the cases.
CTRL	Isoglycemic clamp	Healthy control subjects matched individually to the cases.
CTRL	Gastric emptying rate	Healthy control subjects matched individually to the cases.

Primary Outcome Measures

Name	Time	Method
Progress in Incretin effect in patients with T2DM compared with healthy subjects	4 hours

Secondary Outcome Measures

Name	Time	Method
GIP and GLP-1 responscurvs	4 hours

Trial Locations

Locations (1)

Endokrinologisk afd. J, Herlev Hospital; 🇩🇰 Herlev, Region Hovedstaden, Denmark