Assessment of Liver Glucose Metabolism in Diabetic Subjects

Study Overview
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Brief Summary
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Type 2 diabetes is associated with hepatic insulin resistance. One consequence of insulin resistance of the liver is an altered hepatic glucose metabolism. This study investigates whether the whole body (M-value) and hepatic insulin sensitivity obtained by hyperinsulinemic euglycemic clamp is influenced by a preceding intravenous glucose tolerance test (Botnia Clamp) in subjects with type 2 diabetes.

Detailed Description
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The hyperinsulinemic euglycemic clamp represents the gold standard for measuring peripheral insulin sensitivity. The insulin sensitivity is described by the M-value,which is calculated from glucose infusion rates during the last 30min of the clamp. Glucose is metabolised in the periphery: 50% by neural tissues, 20% by splanchnic bed and liver, 15% by skeletal muscle, 5% by adipose tissue and 10% by blood cells and other tissues. Under hyperinsulinemic conditions there is a strong shift in glucose utilization: 85% skeletal muscle and 15% by neural tissues, splanchnic bed and liver, adipose tissue, blood cells and other tissues. The contribution of skeletal muscle varies with different insulin sensitivity. We now want to investigate whether there is a difference in tissue-specific insulin sensitivity measured from a Botnia clamp (intravenous glucose tolerance test (ivGTT) and following clamp) and a single hyperinsulinemic euglycemic clamp? After a 60min ivGTT blood glucose levels in type 2 diabetic subjects are still elevated compared to baseline. High blood glucose levels can influence several parameters and may also affect insulin sensitivity. Until now, it is not proven, that the clamp preceding ivGTT does not have a significant influence on the M-value.

Official Title
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Assessment of Liver Glucose Metabolism in Diabetic Subjects

Conditions
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Newly Diagnosed Type 2 Diabetes (During the Last 12 Months)

Intervention / Treatment
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* Biological: intravenous glucose tolerance test
* Biological: hyperinsulinemic euglycemic clamp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed type 2 diabetes (during the last 12 months)or non-diabetic subjects Exclusion Criteria: severe chronic diseases hepatitis B, C oder HIV infection malignancies immune suppressive therapy psychiatric illnesses drug or alcohol abuse anemia renal dysfunction

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Botnia clamp<br>hyperinsulinemic euglycemic clamp following intravenous glucose tolerance test | Biological: intravenous glucose tolerance test<br>* Administration of a 30% weight-adapted glucose bolus intravenously.<br>* Other names: ivGTT;Biological: hyperinsulinemic euglycemic clamp<br>* Intravenous administration of 20% glucose and insulin over 3 hours<br>* Other names: HEC;|
| Active Comparator: hyperinsulinemic euglycemic clamp<br>hyperinsulinemic euglycemic clamp without previous intravenous glucose tolerance test | Biological: hyperinsulinemic euglycemic clamp<br>* Intravenous administration of 20% glucose and insulin over 3 hours<br>* Other names: HEC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| M Value in hyperinsulinemic euglycemic clamp | measurement of whole body insulin sensitivity with hyperinsulinamic euglicamic clamp | 3h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin-suppressed endogenous glucose production (liver insulin sensitivity) | Insulin-suppressed endogenous glucose production (liver insulin sensitivity) | 3h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, insulin sensitivity, hyperinsulinemic euglycemic clamp