Effect of Pistachio Intake on Insulin Resistance and Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Hypothesis: Chronic intake of pistachios improves glucose metabolism and insulin resistance status thus contributing to decrease the risk of type 2 diabetes mellitus and its associated abnormalities.

Detailed Description
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In free-living overweight or obese adult with impaired fasting glucose or impaired glucose tolerance we will compare the effects of a pistachio-rich diet or a Mediterranean Diet on: Fasting glucose levels, hemoglobin A1c, insulin, C peptide, HOMA IR, advanced glycation end products and soluble receptor of advanced glycation-end products. Peripheral haemostatic parameters. Plasma inflammatory markers. Lymphocyte expression of toll-like receptors, C peptide, resistin and interleukin-6 in peripheral leukocytes. Lymphocyte glucose transport and expression of glucose transporter 4 in peripheral blood leukocytes. Platelet function including platelet number, mean platelet volume, platelet factor 4 levels and urinary 11-dehydro-thromboxane B2.

Official Title
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Effect of Pistachio Intake on Insulin Resistance and Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Pistachios
* Other: control diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI less than 35 kg/m2. Fasting plasma glucose levels between 100 and 125 mg/dl or Oral glucose tolerance test of 140 to 199 mg/dl. Exclusion Criteria: Diabetes mellitus. Alcohol, tobacco, or drug abuse. Significant liver, kidney, thyroid, or other endocrine diseases. Frequent consumption of nuts or known history of allergy to them. Use of plant sterol, oral antidiabetic drugs, supplemental use of phyllium, fish oil supplements and multivitamins, vitamin E or other antioxidant supplements. Bad dentures, implying difficulty to chew pistachios. Being pregnant or wishing to become a pregnant 6 months before or during the study, lactating 6wk before or during the study. Following vegetarian or weight loss diets. Other medical or social conditions that difficult the compliance to the intervention.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control diet<br>Low-fat normocaloric diet (30% fat, 55% carbohydrates, 15% proteins) | Other: control diet<br>* Participants are randomised crossover clinical trial of 4-months trials separated by a 2-week washout period. Total duration of intervention and follow-up is nine months.<br>|
| Experimental: Pistachio diet<br>Diet supplemented with 2 ounces of pistachio (35% fat, 50% carbohydrates adn 15% protein) | Dietary Supplement: Pistachios<br>* Participants are randomised crossover clinical trial of 4-months trials separated by a 2-week washout period. Total duration of intervention and follow-up is nine months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in circulating levels of glucose and insulin according to the intervention arm | Measurement of circulating glucose and insulin levels and cellular glucose uptake | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in inflammatory, oxidative and metabolic risk markers related to glucose/insulin metabolism according to the intervention arm | Cpeptide, resistin, IL-6, IL-18, Ghrelin, leptin, adiponectin, GLP-1 and oxidized LDL will be measured. | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in haemostatic parameters according to the intervention arm | Tissue factor, fibrinogen, PAI-1, vWF will be measured. | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in HL and LDL size according to the intervention arm | Plasmi lipoprotein size will be measured by polycacrylamide gradient gel electrophoresis | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes in advanced glycation end products according to the intervention arm | Advanced glycation end products and soluble receptor of advanced glycation-end produtcs will be measured | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in gene expression in the peripheral cells according to the intervention arm | RNA from peripheral leukocytes will be isolated for the subsequent measurements of changes in gene expression of toll-like receptors, GLUT-4, C-peptide, resistin adn IL-6, and genes involved in telomere maintenance and oxidation | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in cellular glucose uptake according to the intervention arm | Glucose uptake and GLUT4 protein levels will be assessed in peripheral leukocytes | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in platelet function according to the intervention arm | Platelet number, mean platelet volume and platelet factor 4 in blood, and urinary levels of 11-dehydro-thromboxane B2 will be assessed. | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first and second intervention arm | 
| Changes from baseline in telomeric length of leukocytes (LTL) | Telomere lenght will be evaluated as a biomarker of biological age and general health status. Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D) increasing the probability of beta-cell senescence, leading to reduced cell mass and decreased insulin secretion. | Participants will be followed for 9 months. Measurements will be done before and after 4 months of the first intervention arm. Measurements will be not analysed after the second period due to expected carry-over effect. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pistachio intake, insulin resistance, type 2 diabetes mellitus