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

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.

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