The purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic nephropathy.

• Cardiovascular disease is the leading cause of deaths in diabetic population with diabetic nephropathy.
• Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting-enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB)
• Diabetic patients at increased cardiovascular risk should receive an antiplatelet agent for primary prevention.

Methods:

An open label,randomized, two period cross-over design study, involving patients with type 2 diabetes and diabetic nephropathy. After a 4 weeks wash out period for ACE inhibitors or Angiotensin receptor blockers (week 0, baseline) 60 patients will be randomized to receive ramipril(10 mg) only or ramipril (10 mg) and clopidogrel (75mg) for 12 weeks exchanging their treatment for a further 12 weeks, after a 2 week wash out period for clopidogrel. Patients will be examined and measurements will be taken at baseline (week 0), and at the end of 12, 14, and 26 weeks.

Inclusion Criteria: type 2 diabetes patients with diabetic nephropathy in the range of micro- or macroalbuminuria and

• HbA1c(glycosylated haemoglobin A1c <7%
• Blood pressure ≤130/80 mmHg
• LDL (Low Density Lipoproteins) <100 mg/dl
• Informed consent

Exclusion Criteria:

• patients with diabetic nephropathy and estimated GFR <30ml/min with Modification of Diet in Renal Disease equation (MDRD equation)
• baseline potassium > 5.2 meq/L
• patients with nephrotic proteinuria defined as albumine to creatinine ratio (ACR)> 3.5 g/g or as proteinuria >3.5 g per 1.73 m2 per 24 hours
• history or evidence of non-diabetic kidney disease
• history of stroke, peripheral artery disease, coronary artery disease
• history or evidence of a secondary form of hypertension
• history of severe hepatic failure, malignancy, severe endocrinopathy,autoimmune disease or chronic inflammatory disease
• any known bleeding or platelet disorder or platelets <100.000/μL
• heart failure in New York Heart Association(NYHA) functional class II-IV
• inability or unwillingness on the part of the patient to sign the Patient Consent Form
• known hypersensitivity to ramipril or to clopidogrel
• Women of child-bearing potential
• use of oral anticoagulants or other antithrombotic treatment
• use of glitazones
• patients receiving statins should be on a stable dose of at least 3 months prior to study initiation and dose should be constant during the study
• any surgical or medical condition which in the opinion of the investigator may expose the patient to a higher risk in participation in the study