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

Institute for Clinical and Experimental Medicine

Status: Completed

Conditions: Insulin Resistance; Type 2 Diabetes

Treatments: Drug: Saline; Procedure: Hyperinsulinaemia; Drug: Losartan

Study type: Interventional

Funder types: Other

Identifiers

NCT01011062

CDS01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: Male

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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23 participants in 3 patient groups, including a placebo group

Hyperinsulinaemia

Experimental group

Description:

Hyperinsulinaemic (1 mIU/kg/min) euglycaemic (5 mmol/l) clamp

Treatment:

Procedure: Hyperinsulinaemia

Losartan + hyperinsulinaemia

Experimental group

Treatment:

Drug: Losartan

Procedure: Hyperinsulinaemia

Saline

Placebo Comparator group

Description:

Infusion of Saline as a volume control intervention

Treatment:

Drug: Saline