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

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, Czech Republic
Information provided by:
Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier:
NCT01011062
First received: November 10, 2009
Last updated: NA
Last verified: November 2009
History: No changes posted
  Purpose

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.


Condition Intervention
Insulin Resistance
Type 2 Diabetes
 Procedure: Hyperinsulinaemia
Drug: Losartan
Procedure: Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Acute Angiotensin Receptor Blockade on Insulin Resistance and Selected Cytokines in Adipose Tissue in Type 2 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Institute for Clinical and Experimental Medicine:

Primary Outcome Measures:
  • insulin sensitivity measured as glucose disposal during clamp [ Time Frame: 4 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • plasma adipokines and their expressions in SAT [ Time Frame: at 0 and 240 min of the clamp ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: January 2004
Study Completion Date: August 2009
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hyperinsulinaemia
Hyperinsulinaemic (1 mU/kg/min) euglycaemic (5 mmol/l) clamp
 Procedure: Hyperinsulinaemia
Hyperinsulinaemic (1 mU/kg/min) euglycaemic (5 mmol/l) clamp
Experimental: Losartan + hyperinsulinaemia Procedure: Hyperinsulinaemia
Hyperinsulinaemic (1 mU/kg/min) euglycaemic (5 mmol/l) clamp
Drug: Losartan
Acute administration of losartan 200mg total prior to clamp
Placebo Comparator: Saline
Infusion of Saline as a volume control intervention
 Procedure: Saline
Infusion of Saline as a volume control intervention

Detailed 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 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 MR 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011062

Locations
Czech Republic
Diabetes Center, Institute of Clinical and Experimental Medicine
Prague, Czech Republic, 14021
Sponsors and Collaborators
Institute for Clinical and Experimental Medicine
Ministry of Health, Czech Republic
Investigators
Principal Investigator: Terezie Pelikanova, Prof., MD Diabetes Center, Institute of Clinical and Experimental Medicine
  More Information

No publications provided

Responsible Party: Dagmar Köveslygetyova, Diabetes Center, Institute for Clinical and Experimental Medicine
ClinicalTrials.gov Identifier: NCT01011062     History of Changes
Other Study ID Numbers: CDS01
Study First Received: November 10, 2009
Last Updated: November 10, 2009
Health Authority: Czech Republic: Ethics Committee

Keywords provided by Institute for Clinical and Experimental Medicine:
Adipose tissue
Adipokines

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Losartan
 Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013