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Effect of Flavanol-rich Cocoa on Peripheral and Cerebral Blood Flow in Type 2 Diabetes

Not Applicable
Completed
Conditions
Diabetes
Interventions
Dietary Supplement: High Flavanol Cocoa
Dietary Supplement: Low Flavanol Cocoa
Registration Number
NCT01654172
Lead Sponsor
University of Nottingham
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • Type 2 diabetes
  • Peripheral neuropathy or free from neuropathy
Exclusion Criteria
  • Current foot ulceration
  • Hypertension
  • Anti-hypertensive medications other than thiazide diuretics and ACE inhibitors
  • Ischaemic heart disease
  • Peripheral vascular disease (ABPI ,0.9 &/or impalpable foot pulses)
  • Chronic kidney disease
  • Poor glycaemic control
  • DVT
  • Epilepsy
  • Pregnancy
  • Contraindications to MRI
  • Intolerance to lactose or cow's milk protein

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
High Flavanol CocoaHigh Flavanol CocoaCocoa drink containing \~450mg cocoa flavanols and 10g carbohydrate per serving. Subject consumes 2 servings per day, for 7 days.
Low Flavanol CocoaLow Flavanol CocoaCocoa drink containing \~25mg cocoa flavanols and 10g carbohydrate per serving. Subject consumes 2 servings per day, for 7 days.
Primary Outcome Measures
NameTimeMethod
Change in Fasting Brain Blood FlowDay 0 and after 7d consumption of a cocoa drink

Measured by ASL-MR at Day 0 and after 7d consumption of a cocoa drink to detect a change following intervention

Secondary Outcome Measures
NameTimeMethod
Change in Brain blood flow after acute consumption of cocoa1,3,5 and 8hrs after cocoa consumption

Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

Change in Fasting foot blood flowDay 0 and after 7d consumption of a cocoa drink

Measured using ASL-MR

Change in Foot blood flow after acute consumption of cocoa1,3,5 and 8hrs after cocoa consumption

Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

Change in Blood Flavanol concentrationDay 0 and after 7d consumption of a cocoa drink

Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

Change in Fasting oxidative stress statusDay 0 and after 7 days of consuming a cocoa drink

Oxidative stress assessed by measuring concentration of homocysteine, CRP, 8-isoprostaglandin, arginine and nitric oxide metabolites in the blood.

Change in diabetes controlDay 0 and after 7days of consuming a cocoa drink daily

Assessment made from HbA1c, glucose and insulin concentration in the blood

Trial Locations

Locations (1)

University of Nottingham

🇬🇧

Nottingham, Notts, United Kingdom

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