Hypertension, Type 2 Diabetes Mellitus
Conditions
Keywords
nitric oxide, oxidative stress, diabetes, hypertension, endothelial dysfunction
Brief summary
It has been demonstrated that the nitric oxide production is reduced in type 2 diabetic patients and that cardiovascular complications represent 80% of the causes of death in these patients. As nitric oxide is able to reduce platelet aggregation, increase the relaxation of smooth muscle cells, and reduce plasminogen activator inhibitor-1 and endothelin, we hypothesized that nitric oxide deficiency is responsable for the cardiovascular disease in type 2 diabetes mellitus. Arginine and N-acetylcysteine, precursor and enhancer of the nitric oxide synthesis respectively, are able to increase nitric oxide production. Aim of the study is to evaluate the effect of arginine and N-acetylcysteine administration on arterial blood pressure and different metabolic parameters in patients with type 2 diabetes mellitus and hypertension. Subjects and methods. 24 male subjects, randomly divided in two groups, will be studied. These subjects will undergo a treatment with arginine (1200 mg once a day) plus N-acetylcysteine (600 mg twice a day) or placebo for six months. Basal and final evaluations include: * general examination * ABPM (ambulatory blood pressure monitoring) * HbA1c, total-cholesterol, HDL-cholesterol, LDL-cholesterol, oxidized LDLs, triglycerides, reduced/oxidized glutathione ratio in red blood cells, nitrites/nitrates, asymmetrical and symmetrical dimethyl-arginine, nitrotyrosine, arginine, homocysteine, C-reactive protein, interleukin-6, tumor necrosis factor-α, intercellular and vascular-cell adhesion molecules, plasminogen activator inhibitor-1 and fibrinogen * the ultrasound assessment of the intima-media thickness after endothelium-dependent flow-mediated vasodilation of the brachial artery Expected results. Increase of nitric oxide production and reduction of arterial blood pressure and oxidative parameters.
Interventions
DRUGArginine
1200 mg, once a day
DRUGAcetylcysteine
600 mg twice a day
DRUGPlacebo
3 vials a day
Sponsors
University of Turin, Italy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male subjects * Age between 40 and 70 years * Type 2 diabetes mellitus and hypertension * Mean 24h arterial blood pressure after the wash-out period: systolic \>136mmHg and/or diastolic \>86 mmHh * Written informed consent
Exclusion criteria
* Female subjects * Mean 24h arterial blood pressure after the wash-out period: systolic \>180 mmHg and/or diastolic \>110 mmHg * Secondary hypertension * Significative cardiovascular complications of diabetes * Cancer or severe systemic, hepatic, pulmonary, cardiovascular or diseases * Actual treatment with nitrates, acetylcysteine or arginine * Acetylcysteine hypersensitivity * Psychiatric disturbs, abuse of drugs or alcohol * Low compliance * Absence of written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| arterial blood pressure decrease | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| oxidative parameters decrease | 6 months |
Countries
Italy
Outcome results
None listed