Effect of Angiotensin Receptor Blockade on Insulin Resistance and Adipose Tissue Cytokines in Type 2 Diabetes

Study Overview
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Brief Summary
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The study aims to investigate the effect of acute angiotensin receptor blockade on insulin action/insulin resistance and expressions of selected adipocytokines in subcutaneous adipose tissue in insulin-resistant subjects with type 2 diabetes and healthy controls. Hypothesis: Changes in adipocytokine concentrations and/or expressions and different reactions to acute in vivo induced hyperinsulinemia and angiotensin receptor blockade will be found in patients with type 2 diabetes compared to healthy subjects. A significant relationships between insulin sensitivity and selected adipokines and intracellular fat content and high energy phosphates in soleus muscle will be documented in healthy individuals, while no significant relation will be found in patients with type 2 diabetes.

Detailed Description
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10-15 patients with type 2 diabetes and 10-15 healthy control subjects will be examined on an outpatient basis. The following examination will be carried out in each subject after 12 hrs fasting: Oral glucose tolerance test (75 g of glucose) (in healthy subjects to confirm the normal tolerance of glucose). Evaluation of insulin secretion after 1 mg of glucagon i.v. Hyperinsulinaemic (75 milly-international unit(mIU)/l) euglycemic clamp study lasting 4 hours combined with indirect calorimetry and biopsy of subcutaneous adipose tissue. Hyperinsulinemic (75 mIU/l) euglycemic clamp study lasting 4 hours combined with indirect calorimetry after losartan 100 mg given in the evening and in the morning before the study. Proton and phosphorus magnetic resonance spectroscopy. Before (0 min), at 30 min and in the end of studies c) and d) the blood samples will be taken and biopsies of subcutaneous abdominal adipose tissue will be done.

Official Title
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Effect of Acute Angiotensin Receptor Blockade on Insulin Resistance and Selected Cytokines in Adipose Tissue in Type 2 Diabetes

Conditions
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Insulin Resistance, Type 2 Diabetes

Intervention / Treatment
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* Procedure: Hyperinsulinaemia
* Drug: Losartan
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes treated with oral agents and/or diet Healthy volunteers age- and sex-matched to type 2 diabetes, without any concomitant disease Exclusion Criteria: Type 2 Diabetes treated with insulin clinical evidence of atherosclerotic complications advanced long-term diabetic complications (manifest nephropathy, proliferative retinopathy) other internal disease weight change >10% 3 months prior to study Healthy volunteers fulfilling the criteria of metabolic syndrome weight change >10% 3 months prior to study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperinsulinaemia<br>Hyperinsulinaemic (1 mIU/kg/min) euglycaemic (5 mmol/l) clamp | Procedure: Hyperinsulinaemia<br>* Hyperinsulinaemic (1 mIU/kg/min) euglycaemic (5 mmol/l) clamp<br>|
| Experimental: Losartan + hyperinsulinaemia<br> | Procedure: Hyperinsulinaemia<br>* Hyperinsulinaemic (1 mIU/kg/min) euglycaemic (5 mmol/l) clamp<br>Drug: Losartan<br>* Acute administration of losartan 200mg total prior to clamp<br>|
| Placebo Comparator: Saline<br>Infusion of Saline as a volume control intervention | Drug: Saline<br>* Infusion of Saline as a volume control intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin sensitivity measured as glucose disposal during clamp |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma adipokines and their expressions in SAT |  | at 0 and 240 min of the clamp | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adipose tissue, Adipokines