The Effect of Iloprost on Capillary Recruitment and Insulin Sensitivity in Type 2 Diabetes

Study Overview
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Brief Summary
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This study examines the effects of iloprost - a stable prostacyclin analogue - on insulin-mediated muscle capillary recruitment and whole-body glucose uptake in a cross-over design.

Detailed Description
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In type 2 diabetes impaired insulin-mediated muscle perfusion is thought to contribute to reduced whole-body glucose uptake. This study aims to identify iloprost - a stable prostacyclin analogue - as a possible therapeutic option to increase whole-body glucose uptake via enhancement of muscle perfusion. All participants will be subjected to two hyperinsulinemic-euglycemic clamps; one with and one without simultaneous iloprost infusion in a randomized cross-over design. Microvascular blood volume will be measured by means of contrast-enhanced ultrasonography.

Official Title
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The Effects of Iloprost Infusion on Capillary Recruitment and Whole-body Glucose Uptake in Type 2 Diabetic Patients - a Cross-over Trial.

Conditions
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Diabetes Mellitus, Type 2, Insulin Sensitivity/Resistance

Intervention / Treatment
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* Drug: Iloprost infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Male or female (post-menopausal) Age above 45 years and below 70 years BMI >30 kg/m2 HbA1c < 80 mmol/mol or < 8,6% Subjects must use metformin Stable medication use Stable tension regulation (with or without medication) Subjects should be able to give informed consent Exclusion Criteria: A history of cardiovascular event (Cerebrovascular event, myocardial infarction or pacemaker implantation) Severe-very severe lung emphysema (GOLD stage III-IV) Use of any antibiotics or proton pump inhibitor (PPI) in the past three months Use of any other antidiabetic medication besides metformin (e.g. SU-derivates, insulin) Use of a platelet inhibitor or cumarin derivate during Subjects participated in a lifestyle programme in the past 6 months (diet or exercise)

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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No

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: Iloprost first<br>Cross-over starts with iloprost intervention, then second clamp without iloprost. | Drug: Iloprost infusion<br>* Iloprost is a stable prostacyclin analogue<br>|
| Experimental: Iloprost second<br>Cross-over starts without iloprost intervention, then second clamp with iloprost. | Drug: Iloprost infusion<br>* Iloprost is a stable prostacyclin analogue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of disappearance | Glucose uptake in peripheral tissues during hyperinsulinemic euglycemic clamp | During the clamp | 
| Capillary recruitment | Change in skeletal muscle en myocardial microvascular blood volume upon insulin infusion | Before and during the clamp | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continous cardiovascular monitoring | Diastolic blood pressure | Before and during the clamp | 
| Continous cardiovascular monitoring | Systolic blood pressure | Before and during the clamp | 
| Continous cardiovascular monitoring | Cardiac output | Before and during the clamp | 
| Continous cardiovascular monitoring | Heart rate | Before and during the clamp | 
| Continous cardiovascular monitoring | Stroke volume | Before and during the clamp | 
| Continous cardiovascular monitoring | Systemic vascular resistance | Before and during the clamp | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Capillary recruitment