Effect of Flavanol-rich Cocoa on Peripheral and Cerebral Blood Flow in Type 2 Diabetes
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional

Summary: 
      Cocoa flavanols form part of the family of chemicals (also found in red wine and tea) which
      have aroused interest due to population studies suggesting that diets high in these
      substances might reduce risks of heart disease. In the laboratory, these flavanols have been
      shown to cause blood vessels to widen and blood flow to increase. As dysfunction in this
      ability of blood vessels to widen is now thought to play a central role in the complications
      of diabetes, novel ways to mitigate this are constantly being sought.

      The present study aims to use non-invasive magnetic resonance imaging (MRI) to measure foot
      and brain blood flow before and after 7 days consumption of a cocoa drink high in flavanols,
      in subjects with diabetes, with and without peripheral neuropathy.
    

Detailed description: 
      Cocoa flavanols form part of the family of polyphenols (also found in red wine and tea) which
      have aroused interest due to epidemiological studies suggesting that diets high in these
      substances might reduce risks of heart disease. However, it is difficult to account for all
      sources of polyphenols in these epidemiological studies, and the level of cocoa product
      consumption was generally not well documented. Furthermore, in readily available cocoa
      products, processing may remove most of the flavanols, leading to such products varying
      considerably in flavanol content. Recently, laboratory studies of the effects of cocoa
      flavanols have suggested an effect on the relaxation of smooth muscle in blood vessel walls,
      specifically the element mediated by the endothelium (blood vessel wall). Studies using
      ultrasound methods in healthy volunteers have shown an increase in blood flow in the arm
      following temporary arterial occlusion.

      As endothelial dysfunction is now thought to play a central role in the complications of
      diabetes, novel ways to mitigate this are constantly being sought. It is well recognised that
      diabetic peripheral nerve damage leads to abnormal foot blood flow, including impaired
      superficial skin blood flow, and that this is one of the factors delaying wound healing in
      diabetic foot ulcers (the single largest cost in secondary care diabetes).

      Several techniques are currently used to monitor blood flow to the limbs, including venous
      occlusion plethysmography (VOP), laser Doppler methods and nuclear medicine techniques. These
      techniques have low spatial resolution, low specificity, are labour intensive, or require the
      use of injected radioactive contrast agents (which pose a particular risk to diabetic
      patients). Radiation dose also limits repeat studies.

      The arterial spin labelling magnetic resonance (ASL MR) technique is non-invasive, but yields
      a quantifiable measure of blood flow with high resolution, and allows measurements to be
      repeated several times, as the technique uses no external contrast agents.

      The present study aims to use non-invasive magnetic resonance imaging (MRI) to measure
      peripheral (foot) and brain blood flow at baseline and in response to a cocoa drink high in
      flavanols, in subjects with type 2 diabetes, with and without peripheral neuropathy.

      Subjects will attend an initial screening visit. Measures of HbA1c, kidney function and blood
      pressure will be checked, along with ankle-brachial pressure index (to check for poor
      circulation), foot pulses, and examination for peripheral nerve damage and cardiac
      neuropathy.
    

Intervention name(s): High Flavanol Cocoa; Low Flavanol Cocoa
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Total daily flavanol intake provided by the high flavanol drink is ~900mg
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Diabetes; peripheral neuropathy; Cocoa flavanols