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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Dietary supplement: High Flavanol Cocoa; Dietary supplement: Low Flavanol Cocoa

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Notts
    • Nottingham, Notts, United Kingdom, NG72UH
      • University of Nottingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Flavanol Cocoa; Cocoa drink containing ~450mg cocoa flavanols and 10g carbohydrate per serving. Subject consumes 2 servings per day, for 7 days.	Dietary supplement: High Flavanol Cocoa; Total daily flavanol intake provided by the high flavanol drink is ~900mg
PLACEBO_COMPARATOR: Low Flavanol Cocoa; Cocoa drink containing ~25mg cocoa flavanols and 10g carbohydrate per serving. Subject consumes 2 servings per day, for 7 days.	Dietary supplement: Low Flavanol Cocoa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Brain Blood Flow	Measured by ASL-MR at Day 0 and after 7d consumption of a cocoa drink to detect a change following intervention	Day 0 and after 7d consumption of a cocoa drink

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain blood flow after acute consumption of cocoa	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	1,3,5 and 8hrs after cocoa consumption
Change in Fasting foot blood flow	Measured using ASL-MR	Day 0 and after 7d consumption of a cocoa drink
Change in Foot blood flow after acute consumption of cocoa	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	1,3,5 and 8hrs after cocoa consumption
Change in Blood Flavanol concentration	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	Day 0 and after 7d consumption of a cocoa drink
Change in Fasting oxidative stress status	Oxidative stress assessed by measuring concentration of homocysteine, CRP, 8-isoprostaglandin, arginine and nitric oxide metabolites in the blood.	Day 0 and after 7 days of consuming a cocoa drink
Change in diabetes control	Assessment made from HbA1c, glucose and insulin concentration in the blood	Day 0 and after 7days of consuming a cocoa drink daily

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Mars, Inc.
• Investigators: Principal Investigator: Simon Paige, MD, University Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: July 30, 2012
• First Posted (ESTIMATE): July 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 30, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Diabetes; peripheral neuropathy; Cocoa flavanols
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: 05/Q2401/146