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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011062
• Other study ID #: CDS01
• Status: Completed
• Phase: N/A
• First received: November 10, 2009
• Last updated: October 17, 2013
• Start date: January 2004
• Est. completion date: August 2009

Study information

• Verified date: November 2009
• Source: Institute for Clinical and Experimental Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2009
• Est. primary completion date: October 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Type 2 Diabetes treated with oral agents and/or diet

2. Healthy volunteers age- and sex-matched to type 2 diabetes, without any concomitant disease

Exclusion Criteria:

1. 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

2. Healthy volunteers

• fulfilling the criteria of metabolic syndrome

• weight change >10% 3 months prior to study

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Resistance
• Type 2 Diabetes

Intervention

Procedure:
• Hyperinsulinaemia
Hyperinsulinaemic (1 mIU/kg/min) euglycaemic (5 mmol/l) clamp

Drug:
• Losartan
Acute administration of losartan 200mg total prior to clamp
• Saline
Infusion of Saline as a volume control intervention

Locations

Country	Name	City	State
Czech Republic	Diabetes Center, Institute of Clinical and Experimental Medicine	Prague

Sponsors (2)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine	Ministry of Health, Czech Republic

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin sensitivity measured as glucose disposal during clamp		4 hours	No
Secondary	plasma adipokines and their expressions in SAT		at 0 and 240 min of the clamp	No