Glucose-dependent Insulinotropic Polypeptide - New Role as Blood Glucose Stabilizer?

Study Overview
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Brief Summary
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The purpose of this study is to determine whether glucose-dependent insulinotropic polypeptide (GIP) has a stabilizing function on the blood glucose

Detailed Description
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The aim of the study is to investigate the effect of GIP on the glucagon secretion during hyper-, eu- and hypoglycemia in healthy volunteers, patients with type 1 diabetes mellitus and patients with type 2 diabetes mellitus. From this, we will evaluate GIP's role as blood sugar stabilizer.

Official Title
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Glucose-dependent Insulinotropic Polypeptide - New Role as Blood Glucose Stabilizer?

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: glucose-dependent insulinotropic polypeptide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasians with T1DM (diagnosed according to WHO's criteria) without residual beta cell function (arginine test without increase in c-peptide) in treatment with long acting insulin OR Caucasians with non-insulin treated T2DM (diagnosed according to WHO's criteria) OR Caucasians without first degree relative with diabetes mellitus, with normal fasting plasma glucose and glucose tolerance along with negative islet and GAD-65 autoantibodies AND Normal hemoglobin Informed consent Exclusion criteria: Unwillingness to participate or the wish to leave the present study HbA1c > 9 % Liver disease (ALAT or ASAT > 2 times normal value) Diabetic nephropathy (serum creatinin > 130 microM and/or albuminury) Proliferative diabetic retinopathy (anamnetic) Atherosclerotic heart disease or heart failure (NYHA group III and IV) Anemia Treatment with medicine which cannot be paused for 12 hours Pregnancy and/or breast feeding Fasting plasma glucose > 15 mM on the day of the experiment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy volunteers<br> | Drug: glucose-dependent insulinotropic polypeptide<br>* For the first 20 min of the experiment the volunteers will receive GIP at 4 pmol/kg body weight. For the following 40 minutes the volunteers will receive 2 pmol/kg body weight<br>Drug: Placebo<br>* copy GIP infusion rates<br>|
| Experimental: Patients with Type 1 diabetes mellitus<br> | Drug: glucose-dependent insulinotropic polypeptide<br>* For the first 20 min of the experiment the volunteers will receive GIP at 4 pmol/kg body weight. For the following 40 minutes the volunteers will receive 2 pmol/kg body weight<br>Drug: Placebo<br>* copy GIP infusion rates<br>|
| Experimental: Patients with type 2 diabetes mellitus<br> | Drug: glucose-dependent insulinotropic polypeptide<br>* For the first 20 min of the experiment the volunteers will receive GIP at 4 pmol/kg body weight. For the following 40 minutes the volunteers will receive 2 pmol/kg body weight<br>Drug: Placebo<br>* copy GIP infusion rates<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in glucagon secretion quantified as the difference in plasma glucagon concentration and incremental baseline-subtracted area under the curve (AUC) for plasma glucagon |  | -10, 0, 5, 10, 20, 30, 45, 60 and 90 minutes at each visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference between the amount of infused glucose and the insulin responses |  | will be measured at each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1DM, T2DM, GIP, Glucose-dependent insulinotropic polypeptide, Incretin