Clinical trial NCT01201590: The Effects of Cocoa Flavanols on Insulin Resistance in an 'At-risk' Population
Official title: The Effects of Cocoa Flavanols on Insulin Resistance in at 'At-risk' Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Keywords: Insulin resistance
obesity
cocoa
women
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Mars, Inc.
First posted: 2010-09-14
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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)

Primary outcomes:
measure: Change in Insulin sensitivity 'M' value (mg glucose disposal from the blood/kg body weight/min),
timeFrame: after 28 days of supplementation
Secondary outcomes:
measure: Change in Glucose Oxidation rate
timeFrame: after 28 days of supplementation
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: David Greenfield Physiology Laboratories, University of Nottingham
state: Notts
Study officials:
affiliation: University of Nottingham
name: Ian A Macdonald, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simpson EJ, Mendis B, Dunlop M, Schroeter H, Kwik-Uribe C, Macdonald IA. Cocoa Flavanol Supplementation and the Effect on Insulin Resistance in Females Who Are Overweight or Obese: A Randomized, Placebo-Controlled Trial. Nutrients. 2023 Jan 21;15(3):565. doi: 10.3390/nu15030565.