A Comparison Chocolate With and Without High Cocoa Solids in Patients With Type 2 Diabetes in a Randomised Clinical Trial

Study Overview
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Brief Summary
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Type 2 diabetes is being acknowledged as a potential public health time bomb, whose incidence is predicted to double over the next 10 years in the UK, associated with the rise in obesity and increasing sedentary lifestyles. Increased insulin resistance has been shown to be an important feature of type 2 diabetes (especially in those presenting with obesity and in particular visceral or abdominal obesity). Insulin resistance is implicated as a risk factor of cardiovascular disease and may lead to pancreatic dysfunction through increased β-cell stress in the pancreas. A combination of insulin resistance and pancreatic beta cell failure then leads to type 2 diabetes. The main cause of morbidity and mortality in type 2 diabetes is cardiovascular disease as the condition is associated with impaired vascular functioning and increased levels of oxidation markers. Epidemiological studies suggest dietary flavonoids decrease the risk of death from coronary heart disease, cancer, and stroke. Flavonoid-rich foods include fruits and vegetables as well as tea, red wine, and chocolate. In a cohort of elderly men, cocoa intake was inversely associated with blood pressure and 15-year cardiovascular and all-cause mortality. It has been reported that in healthy humans, consumption of flavanol-rich dark chocolate decreased daytime and night time blood pressure, reduced insulin resistance, and improved nitric oxide dependent vaso-relaxation. Another trial found that cocoa powder increased postprandial insulinaemia in lean young adults. These research papers have led to the hypothesis that chocolate containing high cocoa liquor may help to reduce the risk of developing type 2 diabetes. This study is design as a double-blind, controlled, single center, randomized, parallel design clinical trial. The primary outcome measure is to compare parameters of insulin resistance and glycaemic control in volunteers with type 2 diabetes after consumption of 3 different chocolates (one dark and two milk chocolates) with a secondary outcome of endothelial function, cholesterol profile and oxidative stress. Subjects will undergo medical screening, anthropometry, physical activity and dietary assessments before randomization.

Conditions
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Diabetes Type 2

Intervention / Treatment
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* Other: Cocoa Polyphenols


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: The diagnosis of type 2 diabetes will be based on the WHO guidelines. These are 2 fasting plasma glucose readings of greater than 7.0mmoll-1 or 2 random plasma glucose readings >11mmoll-1 in the absence of symptoms or concurrent illness or medication which might lead to hyperglycaemia (e.g. thiazide diuretics). Or one reading meeting the diagnostic level with the presence of symptoms of polyuria, polydipsia, nocturia, fatigue or blurring of vision. The final diagnostic method of diagnosis type 2 diabetes is a positive oral glucose tolerance test (OGTT) using a 75g glucose load. If doubt exists on the diagnosis of diabetes an OGTT will be performed. Diabetes managed by diet alone or diet and metformin. If metformin is used the dose should have been stable for a minimum of 3 months prior to the start of the study. Hba1c up to and including 9.9% Age 45-75 If female, should be post-menopausal BMI 25-39kgm-2 Patients will have attended a structured group patient education programme (and be on stable medication for hypertension, lipids and gout (if appropriate) for 3 months prior to entry into the study. Subjects will be encouraged to incorporate the chocolate into their diet as advised during the education programme Having obtained his/her or his/her legal representative's informed consent. Exclusion Criteria: Patients with concurrent illness or any changes in medication in the last 3 months. Patients whose diabetes is managed with TZDs, DPP-IV inhibitors, GLP-1 analogues, insulin or sulphonylureas or prandial regulators Patients not wishing to allow disclosure to their GPs. Pregnancy Hba1c at recruiting stage of >10.0% Patient who cannot be expected to comply with treatment Currently participating or having participated in another clinical trial during the last 3 months prior to the beginning of this study Patients who consuming more than 20g/d of chocolate or having a very high polyphenol content of their diet, who are not willing to change their diet Patients taking high dose antioxidant supplements including single and multivitamin preparations including A,C,E. Women on HRT treatment

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High polyphenol milk chocolate<br>High polyphenol milk chocolate containing approximately 1 mg/g of epicatechin | Other: Cocoa Polyphenols<br>* 20g/d of product, two active products provide 20 mg/d epicatechin, on visiting occasions, an acute dose of 40g product to be given<br>|
| Active Comparator: Nestle Noir 70 % chocolate<br>Nestle Noir 70 % chocolate containing approximately 1 mg/g of epicatechin | Other: Cocoa Polyphenols<br>* 20g/d of product, two active products provide 20 mg/d epicatechin, on visiting occasions, an acute dose of 40g product to be given<br>|
| Placebo Comparator: Low polyphenol milk<br>Low polyphenol milk control (matched to product 1 as closely as possible for milk content, carbohydrate, fat and calories, made from cocoa butter, sugar, milk powder and small amount of cocoa liquor to improve taste, giving approximately 0.05mg/g epicatechin. | Other: Cocoa Polyphenols<br>* 20g/d of product, two active products provide 20 mg/d epicatechin, on visiting occasions, an acute dose of 40g product to be given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Insulin Resistance (HOMA) Between Treatments After 12 Weeks of Product Intake | HbA1c with measurement of plasma glucose and insulin (to determine HOMA index) at the 84th day after product intake minus value at baseline (1st day of product intake. Insulin resistance is defined by a HOMA index > 2.4 | 84th day of product intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function After 12 Weeks of Product Intake | Endothelial function is assessed from arterial stiffness measurements at the 84th day minus the value at baseline (1st day of product intake) | 84th day of product intake | 
| Cholesterol Profile After 12 Weeks of Product Intake | Cholesterol profile is assessed from plasma HDL, LDL and total cholesterol measurements at the 84th day of product intake | 84th day of product intake | 
| Oxidative Stress After 12 Weeks of Product Intake | Oxidative stress is assessed from measurements of plasma markers (High sensitivity CRP, IL-1, IL-6, and alpha-TNF) at the 84th day of product intake | 84th day of product intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes type 2, insulin resistance, glycaemic control, Endothelial function, Cocoa Polyphenols