Clinical trial NCT01011062: Effect of Angiotensin Receptor Blockade on Insulin Resistance and Adipose Tissue Cytokines in Type 2 Diabetes
Official title: Effect of Acute Angiotensin Receptor Blockade on Insulin Resistance and Selected Cytokines in Adipose Tissue in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Type 2 Diabetes
Keywords: Adipose tissue
Adipokines
Lead sponsor: Institute for Clinical and Experimental Medicine
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Czech Republic
First posted: 2009-11-11
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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 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.

Eligibility 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

Primary outcomes:
measure: insulin sensitivity measured as glucose disposal during clamp
timeFrame: 4 hours
Secondary outcomes:
measure: plasma adipokines and their expressions in SAT
timeFrame: at 0 and 240 min of the clamp
Other outcomes:
Locations:
city: Prague
country: Czech Republic
facility: Diabetes Center, Institute of Clinical and Experimental Medicine
Study officials:
affiliation: Diabetes Center, Institute of Clinical and Experimental Medicine
name: Terezie Pelikanova, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: