Cocoa/Carob Polyphenols and Postprandial Changes in Type 2 Diabetes

Study Overview
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Brief Summary
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The aim of this is study is to evaluate the effects of a single intake of a mixture of cacao and carob (rich in high molecular weight polyphenols) in postprandial metabolism in subjects with type 2 diabetes. Studies on the effects of polyphenols on postprandial (glucidic and lipidic) metabolism have commonly been performed in animal models and have used food extracts, ignoring high molecular weight polyphenols as relevant bioactive compounds. In this study, the potential of this kind of polyphenols for regulating postprandial disturbances in type 2 diabetes subjects, since these alterations increased the cardiovascular risk in these subjects, will be evaluated. The study has been designed in order to differentially evaluate the effect of intact polyphenols and that of microbial-derived phenolic metabolites.

Detailed Description
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Twenty-five subjects with a recent diagnosis of type 2 diabetes will be recruited. Detailed inclusion and exclusion criteria are provided below. The whole intervention has been divided in 3 treatments A, B and C, performed every 2 weeks in randomized order for each subject. In every treatment, subjects will attend to the Unit of Human Nutrition of the ICTAN-CSIC in fasting state and they will receive a high-sugar high-fat breakfast. Treatment A will be used as control and will only consist of breakfast. Treatment B is characterized by the administration of a mixture of cocoa and carob solved in milk together with breakfast. In treatment C, volunteers will consume the same amount of product 10 hours before attending to their visit, where the breakfast will be administrated once again. Food and drinks provided in the three visits (including milk used in treatment B) will be similar. The aim of treatment B is to elucidate the role of intact polyphenols, while treatment C will evaluate the effect of microbial-derived polyphenol metabolites. Blood samples will be collected before breakfast and at times 60-120-180-240-270 min. Urine will be collected during their permanence at the Unit of Human nutrition of the ICTAN-CSIC. Feces will be collected as soon as they are generated after receiving treatments A and C. The following determinations will be performed in blood samples collected at different periods: glucose, insulin, triglycerides, uric acid, GLP-1, hepatic enzymes. Urine and feces will be used to evaluate phenolic metabolites. Additionally, a satiety test will be provided. It is expected that cocoa and carob supplementation, as compared to the control treatment, causes significant modifications in all the parameters indicated. Nevertheless, the primary outcome of this study is the decrease in postprandial insulin.

Official Title
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Evaluation of Postprandial Effects of High Molecular Weight Polyphenols in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Other: No product (A)/mixture of coca and carob together with breakfast (B)/mixture of coca and carob 10 h before breakfast (C)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes during the last 2 years and current treatment with metformin Overweight or obesity (IMC = 26-40 kg/m2) Exclusion Criteria: Subjects with a pharmaceutical treatment set to modify blood pressure, lipid profile or glucose. Subjects with diagnoses of cardiovascular diseases or thyroid diseases. Values above the following ones: glucose, > 125 mg/dL; triglycerides, > 350 mg/dL; total cholesterol, > 280 mg/dL; systolic blood pressure, > 150 mmHg; diastolic blood pressure, > 100 mmHg Previous bariatric surgery. Volunteers currently participating in other studies or weight loss plans. Pregnant or breastfeeding women. Adherence to vegetarian diets or usual consumption of dietary supplements. Intolerance or allergy to some of the foods provided in the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A: control period; B: mixture of cocoa and carob consumed together with breakfast; C: mixture of cocoa and carob consumed 10 h before breakfast. All the subjects will pass the three treatments, in randomized order. The three periods will be separated by a two weeks washing period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>All subjects will receive a high-fat high-sugar breakfast in three different days. They will not consume any additional product (1), they will receive the mixture of coca and carob together with breakfast (2) or they will receive the mixture of coca and carob 10 h before breakfast (3). | Other: No product (A)/mixture of coca and carob together with breakfast (B)/mixture of coca and carob 10 h before breakfast (C)<br>* The subjects will receive, after overnight fasting, a high-fat high-sugar breakfast. In treatment A, they will not receive any additional product; in treatment B, they will receive at the same time a mixture of coca and carob; in treatment C, they will receive the mixture of coca and carob 10 h before breakfast. A total of 6 blood samples will be collected during each visit: 0-30-60-120-180-240-270 min. Urine samples will be collected during the permanence of the subjects in the Unit of Human Nutrition. Feces will be collected the first time they are generated after treatments A and C. Both interventions will be separated by two weeks. Subjects will be instructed not to modify their dietary habits during the development of the study, but during the 72 h before each visit they will have to restrict the intake of polyphenol-rich foods (a detailed list will be provided).<br>|
| Experimental: 2<br>All subjects will receive a high-fat high-sugar breakfast in three different days. They will not consume any additional product (1), they will receive the mixture of coca and carob together with breakfast (2) or they will receive the mixture of coca and carob 10 h before breakfast (3). | Other: No product (A)/mixture of coca and carob together with breakfast (B)/mixture of coca and carob 10 h before breakfast (C)<br>* The subjects will receive, after overnight fasting, a high-fat high-sugar breakfast. In treatment A, they will not receive any additional product; in treatment B, they will receive at the same time a mixture of coca and carob; in treatment C, they will receive the mixture of coca and carob 10 h before breakfast. A total of 6 blood samples will be collected during each visit: 0-30-60-120-180-240-270 min. Urine samples will be collected during the permanence of the subjects in the Unit of Human Nutrition. Feces will be collected the first time they are generated after treatments A and C. Both interventions will be separated by two weeks. Subjects will be instructed not to modify their dietary habits during the development of the study, but during the 72 h before each visit they will have to restrict the intake of polyphenol-rich foods (a detailed list will be provided).<br>|
| Experimental: 3<br>All subjects will receive a high-fat high-sugar breakfast in three different days. They will not consume any additional product (1), they will receive the mixture of coca and carob together with breakfast (2) or they will receive the mixture of coca and carob 10 h before breakfast (3). | Other: No product (A)/mixture of coca and carob together with breakfast (B)/mixture of coca and carob 10 h before breakfast (C)<br>* The subjects will receive, after overnight fasting, a high-fat high-sugar breakfast. In treatment A, they will not receive any additional product; in treatment B, they will receive at the same time a mixture of coca and carob; in treatment C, they will receive the mixture of coca and carob 10 h before breakfast. A total of 6 blood samples will be collected during each visit: 0-30-60-120-180-240-270 min. Urine samples will be collected during the permanence of the subjects in the Unit of Human Nutrition. Feces will be collected the first time they are generated after treatments A and C. Both interventions will be separated by two weeks. Subjects will be instructed not to modify their dietary habits during the development of the study, but during the 72 h before each visit they will have to restrict the intake of polyphenol-rich foods (a detailed list will be provided).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial insulin | Changes of postprandial insulin as result of supplementation with cocoa and carob | Up to two months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose | Changes of blood glucose as result of supplementation with cocoa and carob. | Up to four months | 
| Postprandial triglycerides | Changes of blood triglycerides as result of supplementation with cocoa and carob. | Up to four months | 
| Postprandial uric acid | Changes of blood uric acid as result of supplementation with cocoa and carob. | Up to four months | 
| Postprandial GLP-1 | Changes of blood GLP-1 as result of supplementation with cocoa and carob. | Up to five months | 
| Postprandial phenolic metabolites | Changes of urinary and fecal phenolic metabolites as result of supplementation with cocoa and carob. | Up to six months | 
| Satiety measured by a Visual Analogue Scale (see Description for details) | Changes of satiety as result of supplementation with cocoa and carob. This will be determined by the CSS, composite satiety score. This is a value obtained from a formula once the subject has filled in, in a visual analogue scale, the answer to different questions regarding hunger and satiety. The answers go from 1 to 10 (each mark corresponding to a similar distance in the scale). The final CSS value goes also from 1 to 10, with 1 meaning the lowest satiety and 10 meaning the highest one. | Up to three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polyphenols, Type 2 diabetes, Cocoa, Carob, Postprandial response, Insulin resistance, Microbial metabolites