The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of GIP

Study Overview
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Brief Summary
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In patients with type 2 diabetes, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has lost its insulinotropic activity, but more so after continuous versus bolus administration. The design was a two-way crossover design comparing repeated bolus injection and continuous infusion of GIP under hyperglycaemic clamp conditions. Patients were age- gender- and weight-matched with type 2 diabetes, first degree relatives of such patients, and healthy subjects. Investigators performed a: Oral glucose challenge; hyperglycemic clamp (8.5 mmol/l) with two repeated GIP bolus administrations (50 pmol/kg body weight at 30 and 120 min); and hyperglycemic clamp with continuous administration of GIP (2 pmol.kg-1.min-1 from 30-180 min). To answer the question, whether rapid tachyphylaxis occurs with regard to the insulinotropic action of GIP, investigators studied type 2-diabetic patients, their first-degree relatives, and healthy controls under hyperglycaemic clamp conditions with two GIP bolus injections 90 min apart, and compared this to a continued intravenous infusion of GIP.

Official Title
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The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of Glucose-dependent Insulinotropic Polypeptide (GIP) in Patients With Type 2 Diabetes is Not Caused by Rapid Tachyphylaxis

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: GIP Bolus
* Drug: GIP Clamp
* Procedure: Oral glucose tolerance test (OGTT)
* Procedure: hyperglycemic clamp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Exclusion of pregnancy Exclusion of impaired glucose tolerance or type 2 diabetes in metabolical healthy subjects current diagnosis of type 2 diabetes according to the guidelines of the German Diabetes Association (DDG) ( Kerner et al . 2001) in subjects of diabetes group fasting glucose ≤ 150 mg/dl Body-mass-index ≥ 20 kg/m² Written consent Exclusion Criteria: Type 1 diabetes Impaired glucose tolerance or Type 2 diabetes in metabolical healthy subjects Ketone bodies urine diagnostics at least ++ Acidosis Fasting blood glucose > 150 mg/dl Body-mass-index < 20 kg/m² No written consent Pregnancy or unsafe contraception in women before menopause Active malignancy Angina as current, unsolved clinical problem Inadequately treated or untreated arterial hypertension ( > 160 mmHg systolic and / or > 95 mmHg diastolic ) Infection / fever > 37.5 ° C Treatment with glucocorticoids Insulin therapy within the last three months Anemia with a hemoglobin level < 12 g/dl Liver function limitations Renal impairment ( serum creatinine > 1.5 mg/dl ) Alcohol or drug abuse Participation in clinical trials in the last 3 months Inability or unwillingness to comply with the requirements of the Protocol Known hypersensitivity to GIP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral glucose tolerance test<br>An oral glucose challenge (75 g) | Procedure: Oral glucose tolerance test (OGTT)<br>* an oral glucose challenge (75 g)<br>|
| Active Comparator: GIP Bolus<br>Hyperglycemic clamp (capillary venous glucose concentration   8.5 mmol/l) with two repeated intravenous bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp | Drug: GIP Bolus<br>* bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp<br>Procedure: hyperglycemic clamp<br>* a hyperglycemic clamp (capillary venous glucose concentration   8.5 mmol/l)<br>|
| Active Comparator: GIP Infusion<br>Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min | Drug: GIP Clamp<br>* hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min<br>Procedure: hyperglycemic clamp<br>* a hyperglycemic clamp (capillary venous glucose concentration   8.5 mmol/l)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretory response after GIP bolus or infusion. |  | 210 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-Like Peptide 1 (GLP-1), Incretin, Insulin secretion, Tachyphylaxis