To Investigate the Effect of Rosiglitazone and Ramipril on Pre-clinical Vasculopathy in Diabetes and IGT Patients
Condition: Diabetes; Impaired Glucose Tolerance
MeSH terms: Vascular Diseases; Glucose Intolerance
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim is to examine whether pharmacological interventions with thiazolidinedione and
      angiotensin converting enzyme (ACE) inhibitors can reverse pre-clinical vasculopathy in newly
      diagnosed diabetic and IGT individuals.
    

Detailed description: 
      The burden of diabetic vasculopathy on the global population is enormous and ever growing.
      Besides the well-known microvascular complications in type 2 diabetes (T2DM), there is a
      growing epidemic of macrovascular complications. People with T2DM have a higher risk of death
      from cardiovascular (CV) diseases than persons without diabetes. Like diabetes, impaired
      glucose tolerance (IGT) individuals also have associated risk of developing macrovascular
      complications. This calls for an early detection and intervention in patients with T2DM as
      well as IGT, not only to delay progression of IGT to T2DM but also to treat early
      macrovascular diseases in both groups. The traditional therapeutic approaches of T2DM
      emphasise on glycaemic control, which limits microvascular diseases but lacks an established
      benefit in macrovascular diseases. Type 2 diabetes is a metabolic disorder characterised by
      dyslipidaemia, hypertension, and hypercoagulability in addition to hyperglycaemia and
      hyperinsulinaemia. Each of these abnormalities plays an important role in diabetic
      vasculopathy and provides targets for therapy. Understanding the mechanisms of diabetic
      vasculopathy and instituting therapy guided by emerging evidences would improve outcomes in
      patients with T2DM and IGT.

      In recent years, special attention has been devoted to both thiazolidinediones (TZDs) and
      angiotensin converting enzyme (ACE) inhibitors when TRIPOD study demonstrated that
      troglitazone may reduce the rate of progression to diabetes in women diagnosed with
      gestational diabetes and HOPE Study showed that ramipril may delay the onset of diabetes. The
      TZDs are novel insulin-sensitising antidiabetic agents, which also have vasculoprotective
      properties. Rosiglitazone, one of the members of TZD family, improves insulin sensitivity and
      may have a beta cell cytoprotective effect. The ACE inhibitors reduce both microvascular and
      macrovascular complications in diabetes and appear to improve insulin sensitivity and glucose
      metabolism. Ramipril, an ACE inhibitor, has direct effects on the
      renin-angiotensin-kallikrein system and may play an important role in the prevention of
      diabetes through effects on beta cell and by vascular and metabolic effects on muscle that
      may amplify the effects of insulin. Previous studies showed that newly diagnosed untreated
      T2DM/IGT and hypertensive Malay patients had early manifestations of preclinical vasculopathy
      and potentially increased risk for development of macrovascular diseases. The aim of this
      study is to investigate whether pharmacological interventions with rosiglitazone and ramipril
      can reverse pre-clinical vasculopathy in newly diagnosed untreated T2DM and IGT patients.
    

Intervention name(s): Rosiglitazone; Ramipril
Intervention type(s): Drug; Drug
Intervention MeSH terms: Rosiglitazone; Ramipril
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Rosiglitazone; Ramipril; Impaired glucose tolerance; Arterial stiffness; Diabetic vasculopathy