Omacor for the Treatment of Vascular Dysfunction in Patients With Type 2 Diabetes Mellitus
Condition: Atherosclerosis; Type 2 Diabetes Mellitus
MeSH terms: Atherosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of the study is to determine whether a 6-week treatment with 4 g Omacor/day
      improves the baseline and postprandial endothelial function (after a high-fat meal) in
      patients with type 2 diabetes mellitus.
    

Detailed description: 
      Patients with type 2 diabetes mellitus (T2DM) have a 2 to 5-fold increase in cardiovascular
      mortality compared to non-diabetics.

      Endothelial dysfunction (ED) is an early messenger of atherosclerosis and is present in
      states showing a high cardiovascular (CV) risk, such as active and passive smoking,
      dyslipidemia, arterial hypertension, obesity, hyperhomocysteinemia, coronary artery disease,
      congestive heart failure and type 1 and type 2 diabetes mellitus. Endothelial function is a
      variable with a large day-to-day variation and shows great excursions even within one day.
      Several factors might play a role such as hormonal status, physical activity, sleep quality,
      but the most important seems to be the postprandial state. Postprandial ED was demonstrated
      not only in patients with CV disease or diabetes, but even in healthy subjects. A large body
      of evidence has accumulated showing distinctive and cumulative effects of hyperglycemia and
      hypertriglyceridemia on postprandial ED. Since postprandial dysmetabolism was linked to CVD,
      ED was proposed to be the mechanism connecting them. Considering that the postprandial state
      covers most of our daytime, interventions targeting a reduction in postprandial ED might play
      a decisive role in atherosclerosis prevention.

      For the treatment of postprandial ED several therapeutical approaches have been suggested
      such as folic acid, tetrahydrobiopterin, vitamins C and E and statins.

      Some properties of omega-3 fatty acids suggest that such an impairment of postprandial
      endothelial dysfunction could be prevented by treatment with Omacor® and the purpose of our
      study is to demonstrate that a six-week therapy with Omacor prevents endothelial dysfunction
      in fasting state and following a high-fat meal.

      Several controlled clinical studies conducted in persons with TM2DM or after myocardial
      infarction have shown that consumption of omega-3 long chain polyunsaturated fatty acids (n-3
      PUFA) have several beneficial effects such as: lowers risk of primary cardiac arrest, reduces
      triglyceride levels, increases high-density lipoprotein levels, reduces platelet
      aggregability, acts anti-inflammatory and immune-modulating, lowers blood pressure and
      improves endothelial function.

      Consumption of n-3 fatty acids was shown to positively influence platelet, fibrinolytic and
      vascular function in hypertensive type 2 diabetic patients. Mediterranean- style diet
      restores markers of endothelial dysfunction and inflammation in persons with metabolic
      syndrome and improves endothelial function in hypercholesterolemic men.

      Since Omacor contains in high-dose purified n-3 fatty acids eicosapentaenoic and
      docosahexaenoic acid (EPA and DHA), our first hypothesis is that a 6-week therapy with 4g/d
      Omacor improves fasting endothelial function in persons with T2DM.

      In patients with T2DM, a three-week diet with a high amount of polyunsaturated fatty acids
      compared to a diet with a high amount of monounsaturated fatty acids, produces a
      significantly lower increase in postprandial lipemia after an oral fat load. Since
      postprandial lipemia induces transient endothelial dysfunction, our second hypothesis is that
      treatment with Omacor prevents postprandial impairment of endothelial function after a high
      fat meal.
    

Intervention name(s): Omacor
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: flow-mediated vasodilatation; endothelial dysfunction; omega-3 fatty acids; type 2 diabetes mellitus; postprandial state