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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: control diet; Dietary supplement: Pistachios

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Tarragona
    • Reus, Tarragona, Spain, 43201
      • Human Nutrition Unit, Faculty of Medicine, Rovira i Virgili University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control diet; Low-fat normocaloric diet (30% fat, 55% carbohydrates, 15% proteins)	Other: control diet; 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.
Experimental: Pistachio diet; Diet supplemented with 2 ounces of pistachio (35% fat, 50% carbohydrates adn 15% protein)	Dietary supplement: Pistachios; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Institut Investigacio Sanitaria Pere Virgili
• Collaborators: Western Pistachio Association
• Investigators: Principal Investigator: Monica Bullo, Dra., Institut Investigacio Sanitaria Pere Virgili

Publications and helpful links

General Publications

• Hernandez-Alonso P, Salas-Salvado J, Baldrich-Mora M, Mallol R, Correig X, Bullo M. Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects. Nutr Metab Cardiovasc Dis. 2015 Apr;25(4):396-402. doi: 10.1016/j.numecd.2015.01.013. Epub 2015 Feb 7.
• Hernandez-Alonso P, Salas-Salvado J, Baldrich-Mora M, Juanola-Falgarona M, Bullo M. Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial. Diabetes Care. 2014 Nov;37(11):3098-105. doi: 10.2337/dc14-1431. Epub 2014 Aug 14.
• Hernandez-Alonso P, Canueto D, Giardina S, Salas-Salvado J, Canellas N, Correig X, Bullo M. Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects. J Nutr Biochem. 2017 Jul;45:48-53. doi: 10.1016/j.jnutbio.2017.04.002. Epub 2017 Apr 12.
• Hernandez-Alonso P, Giardina S, Salas-Salvado J, Arcelin P, Bullo M. Chronic pistachio intake modulates circulating microRNAs related to glucose metabolism and insulin resistance in prediabetic subjects. Eur J Nutr. 2017 Sep;56(6):2181-2191. doi: 10.1007/s00394-016-1262-5. Epub 2016 Jul 6.
• Canudas S, Hernandez-Alonso P, Galie S, Muralidharan J, Morell-Azanza L, Zalba G, Garcia-Gavilan J, Marti A, Salas-Salvado J, Bullo M. Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial. Am J Clin Nutr. 2019 Jun 1;109(6):1738-1745. doi: 10.1093/ajcn/nqz048.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Actual): February 11, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: type 2 diabetes mellitus; insulin resistance; pistachio intake
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: PV11059S