The Effects of Cocoa Flavanols on Insulin Resistance in an 'At-risk' Population

Study Overview
=================
Brief Summary
-----------------
The aim of the current study is to investigate the ability of antioxidants found in cocoa ('flavanols') to increase the body's sensitivity to the hormone insulin. 32 overweight or mildly obese women, who are otherwise healthy, will be recruited. Subjects will attend the laboratory on 3 occasions after fasting from midnight. The 1st visit is a medical screening, with laboratory visits 2 and 3 separated by 4 weeks, during which time subjects will consume a cocoa drink (containing either high or low amounts of flavanols) twice a day. Subjects will record their food intake for 3-days before visit 2 and in week 3 of consuming the cocoa. They will also eat a diet of standard macronutrient composition for 3 days before visits 2 and 3. During the 5 hour laboratory visits, subjects will have a scan to assess their body composition using a low-dose x-ray machine (Dual Energy X-ray Absorptiometry; DEXA), and have their insulin sensitivity measured using a 3 hour hyperinsulinemic, euglycaemic Clamp.

Detailed Description
-----------------
Background; Overweight and mild obesity are associated with insulin resistance and mild elevations in lipid risk factors which are not usually sufficiently abnormal to merit treatment. Such people are encouraged to lose weight to reduce their risk of progressing to type 2 diabetes and coronary heart disease, but there is clearly a potential role for dietary modifications to maximize any potential benefit of this weight loss. Cocoa flavanols (CF) are known to have vascular effects which might enhance substrate delivery to metabolically active tissues, and thus improve insulin sensitivity. Aims; This randomized, double blind, placebo controlled, parallel design study aims to investigate the longer term effects of CF intake on insulin sensitivity. It is hypothesized that studying otherwise healthy overweight and mildly obese subjects, with evidence of fasting insulin resistance, would show whether there was potential benefit of CF in an 'at risk' population. Experimental protocol and methods; 32 overweight or obese women (Body Mass Index 27-35), who are otherwise healthy, will be recruited onto the study. They will attend the 'David Greenfield Human Physiology' laboratories on 3 convenient mornings, following an overnight fast. The 1st visit is a medical screening and will involve signing a consent form, completing a medical screening and food frequency questionnaire, having height, weight, hip/waist circumference measurements taken and a 10ml sample of blood taken for routine analysis. Subjects will then be asked to complete a 3-day diet diary for macronutrient assessment and to consume a diet providing 50% of energy as carbohydrate for 3 days prior to the 2nd laboratory visit. This 2nd visit will involve having a DEXA body composition scan and a 3-hour hyperinsulinaemic, euglycaemic glucose clamp. Starting on the following morning, subjects will then consume a cocoa drink (containing either 450mg or 25mg of CF) twice a day for 28 days. A 3-day diet diary for macronutrient assessment will be recorded during week 3 of taking the cocoa and a standardized diet will be consumed for 3 days prior to the final laboratory visit, as before. This 3rd visit will be identical to visit 2 and occur immediately after 28days of taking the cocoa. Measurable end points Insulin sensitivity 'M' value (mg glucose disposal from the blood/kg body weight.min), Respiratory exchange ratio, Resting metabolic rate, Homeostatic model assessment for insulin resistance (HOMA-IR) Body composition (DEXA) Macronutrient composition of the diet before and during the intervention period

Official Title
-----------------
The Effects of Cocoa Flavanols on Insulin Resistance in at 'At-risk' Population

Conditions
-----------------
Insulin Resistance

Intervention / Treatment
-----------------
* Dietary Supplement: High Flavanol Cocoa
* Dietary Supplement: Low Flavanol Cocoa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: female, aged > 18 years, pre-menopausal, Body Mass Index (BMI)27-35, homeostatic model assessment-Insulin Resistance(HOMA-IR)value > 1.5, daily consumption of caffeine containing foods/drinks Exclusion Criteria: pregnant or breast feeding, any metabolic or endocrine abnormalities, clinically significant abnormalities on screening, fasting glucose > 6.0mmol/l, taking medication other than the contraceptive pill, herbal supplement use, food allergies related to the investigational product (cocoa, peanuts, milk) sensitivity to methylxanthines (e.g., caffeine, theobromine)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Flavanol Cocoa<br>609mg cocoa flavanols per 24g serving | Dietary Supplement: High Flavanol Cocoa<br>* cocoa consumed as a 24g dairy based cocoa drink mix, twice a day (mid-morning & early evening on an empty stomach), for 4 weeks.<br>|
| Placebo Comparator: Low flavanol cocoa<br>13mg cocoa flavanols per 24g serving | Dietary Supplement: Low Flavanol Cocoa<br>* cocoa consumed as a 24g dairy based cocoa drink mix, twice a day (mid-morning & early evening on an empty stomach), for 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin sensitivity 'M' value (mg glucose disposal from the blood/kg body weight/min), | Insulin sensitivity calculated from glucose disposal during a hyperinsulinemic, euglycemic glucose clamp | after 28 days of supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glucose Oxidation rate | Measured by ventilated hood indirect calorimetry during the glucose clamp. | after 28 days of supplementation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, cocoa, women, Insulin resistance