The Effects of Orange Juice on Insulin Sensitivity and Plasma Lipids

Study Overview
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Brief Summary
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The aim of this study is primarily to investigate the ability of antioxidants found in orange juice (OJ) to increase the body's sensitivity to the hormone insulin. Overweight or mildly obese women, who are otherwise healthy, will be recruited. The time commitment for subjects is  14wks. Subjects will attend the laboratory on 5 occasions after fasting from midnight. The 1st is a medical screening. Laboratory visits 2 & 5 will take  5hrs and will be separated by 3 months, during which time subjects will consume 250ml of an orange drink (either OJ or an orange flavoured control drink) once a day. During visits 2 & 5, subjects will have a scan to assess their %body fat using a low-dose x-ray machine, and have their insulin sensitivity measured using a technique called a 'Glucose Clamp'. During the 3hr glucose clamp, subjects receive an infusion of the hormone insulin and a glucose solution directly into their blood stream, with insulin sensitivity determined from the amount of glucose required to maintain blood glucose at normal levels. In addition, a small sample of fat tissue (about the size of a haricot bean) will be taken from underneath the skin of the belly. Subjects will record their food intake for 3-days in weeks 3, 7 and 11 of consuming the drink, and come to the lab for visits 3&4 during weeks 4&8. Laboratory visits 3&4 repeat measurements taken in the 1st (screening) visit.

Detailed Description
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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. Flavonoids are known to have vascular effects which might enhance substrate delivery to metabolically active tissues, and thus improve insulin sensitivity. There are many different dietary sources of flavonoids, with fruits such as apples, berries and citrus being rich sources. However, some researchers have expressed concern that a high dietary intake of 100% juice may contribute to the development of insulin resistance, obesity and the Metabolic Syndrome (Bazzano, Li et al. 2008), although this is not universally accepted (Fujioka, Greenway et al. 2006; O'Neil and Nicklas 2008). To date, there have been no studies investigating the effects of citrus fruits on indices of cardio-metabolic health in people who are presently healthy but are at risk of developing some features of the Metabolic Syndrome. Aims: To investigate the effects of orange juice (OJ) intake on insulin sensitivity, appetite hormones, blood pressure and plasma lipids. In addition we aim to investigate any gene expression changes associated with OJ consumption, in particular in adipose tissue. Experimental protocol and methods: Overweight or obese women (BMI 27-35), who are otherwise healthy, will be recruited onto the study. They will attend the 'David Greenfield Human Physiology' laboratories on 5 convenient mornings, following an overnight fast. The 1st visit is a medical screening and will involve signing a consent form, completing medical screening, food frequency and activity questionnaires, having height, weight, and hip/waist circumference measurements taken and a sample of blood taken for CBC, urea, electrolytes, LFT, TFT, glucose and insulin 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, an adipose tissue biopsy and a 3-hr hyperinsulinemic, euglycemic glucose clamp. Starting on the following morning, subjects will then consume an orange drink (either OJ or a carbohydrate matched orange flavoured drink) once a day for 12 wks. A 3-day diet diary for macronutrient assessment will be recorded during wks 3,7and 11 of taking the drink, and measurements made at screening will be repeated on visits 3 and 4 which will take place in weeks 4 and 8. A standardized diet will be consumed for 3 days prior to the final laboratory visit, as before. This 5th visit will be identical to visit 2.

Official Title
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The Effects of Orange Juice on Insulin Sensitivity and Plasma Lipids

Conditions
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Insulin Resistance, Obesity

Intervention / Treatment
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* Dietary Supplement: orange juice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pre-menopausal or post-menopausal and taking HRT BMI 27-35kg/m2 HOMA-IR value > 1.5 healthy 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 or HRT herbal supplement use, food allergies/intolerances related to the investigational product (citrus juices, fructose) daily consumption of >100ml citrus juices

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orange Juice<br>Orange Juice reconstituted from frozen concerntrate | Dietary Supplement: orange juice<br>* 250ml of orange juice or a sugars matched orange drink<br>|
| Placebo Comparator: Orange drink<br>Sugars matched orange drink | Dietary Supplement: orange juice<br>* 250ml of orange juice or a sugars matched orange drink<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity ('M' value) | Insulin sensitivity (mg glucose disposal from the blood/kg body weight/min)calculated from glucose disposal during a hyperinsulinemic, euglycemic glucose clamp | after 3 months' intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Oxidation rate | Measured by ventilated hood indirect calorimetry | after 3 months' intervention period | 
| High Density Cholesterol | Serum HDL concentration | after 3 months' intervention | 
| Low density cholesterol | Serum LDL concentration | after 3 months' intervention | 
| Gene expression in adipose tissue | Expression of genes related to insulin sensitivity in adipose tissue | after 3 months' intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Women, Orange Juice, Insulin Resistance, Obesity