Effects of ROSIglitazone on Inflammatory Markers and Adipokines in Diabetic Patients Using an Angiotensin Receptor Blocker (TELmisartan) - The ROSITEL Study
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      The purpose of the ROSITEL study is to assess the effects of rosiglitazone, as compared to
      standard oral therapies for diabetes (metformin/sulfonylurea), on inflammatory markers and
      adipokine levels in diabetic patients using an angiotensin receptor blocker (ARB).

      We hypothesize that ARB-treated diabetic patients receiving rosiglitazone will experience
      greater reductions in vascular inflammation and levels of leptin and resistin, associated
      with increased adiponectin levels, compared to a metformin/sulfonylurea regimen, and that
      these benefits will result in part, from greater improvements in insulin sensitivity in the
      rosiglitazone group.
    

Detailed description: 
      Type 2 diabetes is a chronic and progressive disease that is strongly associated with
      all-cause and cardiovascular mortality. The United Kingdom Prospective Diabetes Study (UKPDS)
      demonstrated that glycemic control alone only modestly reduces the risk of macrovascular
      disease among type 2 diabetic patients . Insulin resistance, which has been identified as an
      important underlying or associated factor in the pathogenesis of type 2 diabetes, is the main
      proposed mechanism responsible for the accelerated atherosclerosis noted in this population.

      Evidence continues to accumulate supporting the role of chronic subclinical vascular
      inflammation as a central component in the development of atherosclerosis, insulin resistance
      and type 2 diabetes. Markers of subclinical inflammation, in particular C-reactive protein
      (CRP) and interleukin-6 (IL-6), have been shown to be independent predictors of both diabetes
      and cardiovascular risk. More recently, the visceral adipocyte has been recognized to produce
      a number of metabolically and hormonally active substances, collectively called adipokines.
      The adipokine adiponectin may have antiatherogenic and anti-inflammatory properties. High
      levels of adiponectin seem to be associated with protection against type 2 diabetes and
      atherosclerosis via anti-inflammatory pathways. Unlike adiponectin, leptin and resistin are
      examples of adipokines that seem to be associated with the development of both
      atherosclerosis and insulin resistance.

      Rosiglitazone is a thiazolidinedione drug that is approved for the treatment of type 2
      diabetes. As a nuclear peroxisome proliferator-activated receptor-γ agonist, rosiglitazone
      reduces insulin resistance, thereby sensitizing the liver, muscle, and adipose tissue to the
      actions of circulating insulin. Treatment with rosiglitazone has been demonstrated to
      favourably modify levels of inflammatory biomarkers and adipokines, to attenuate endothelial
      dysfunction, and to reduce coronary events following percutaneous coronary intervention.

      Diabetes and hypertension co-exist in approximately 75% of patients and this combination
      synergistically augments cardiovascular risk. In fact, blood pressure control seems to be of
      greater importance in the prevention of macrovascular disease than is glycemic control.
      Therefore, in patients with diabetes, dual targeting of insulin resistance and blood pressure
      is essential to reduce overall atherosclerotic risk. Recent evidence suggests that
      angiotensin receptor blockers (ARB) in addition to their antihypertensive efficacy may
      directly improve insulin sensitivity. These unique attributes of ARB's may prove particularly
      beneficial when combined with an insulin sensitizer, such as rosiglitazone, in the treatment
      of diabetic patients.

      The rationale therefore of the ROSITEL study is to compare the effects of rosiglitazone to
      usual therapy on adipokine levels, inflammatory markers, and insulin sensitivity in
      ARB-treated diabetic patients with suboptimal glycemic control.
    

Intervention name(s): rosiglitazone; metformin or sulfonylurea
Intervention type(s): Drug; Drug
Other intervention name(s): Avandia
Intervention MeSH terms: Metformin; Rosiglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 Diabetes Mellitus; Thiazolidinediones; Rosiglitazone; Adipokine; Inflammation; Cardiometabolic risk; Angiotensin receptor blocker