A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women With Gestational Diabetes Mellitus

Study Overview
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Brief Summary
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Gestational diabetes mellitus (GDM) is the hyperglycemia with first onset or recognition during pregnancy, of which prevalence has been sharply increased worldwide in the past decades. Nuts offer numerous health benefits, mainly in relation to cardiovascular diseases as well as other chronic conditions. Pistachios have a balanced nutrition profile with lower fat [polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs)], higher protein, fiber (both soluble and insoluble), potassium, phytosterols, γ-tocopherol, vitamin K, xanthophyll carotenoids and rich antioxidant phytochemical constituents (stigmasterol, campesterol, resveratrol, catechins, lutein and zeaxanthin). Recent researches have found that nutritional intervention of the Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios lowered incidence of GDM and other adverse outcomes (urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age newborns) for pregnant women. Another clinical trial compared the acute metabolic effect of pistachios and isocaloric whole-wheat bread in women with GDM, finding significantly improved glucose and insulin responses, higher GLP-1 and lower gastric inhibitory polypeptide (GIP) levels in those consuming pistachios. However, more compelling evidences are still in need to throw light on the long-term effects of pistachio consumption on maternal and offspring's outcomes for GDM patients. Besides, effects of pistachios on the thorough metabolic profile of GDM patients also need to be elucidated. This study aims to further demonstrate the long-term health effects of pistachio consumption on glycemic control, lipid profile, gut hormone responses, inflammatory condition and pregnancy outcomes for women with GDM. The clinical study is a randomized, controlled, two-arm, parallel trial from the diagnosis of gestational diabetes to delivery consisting of six study visits including screening/consent. A total of 80 singleton pregnant women with confirmed diagnosis of GDM will be consecutively recruited, all with the pregestational body mass index (BMI) greater than 24 kg/m2. All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks. According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included women with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. All participants will be followed up in 2 weeks initially and then once every 4-6 weeks until delivery or termination of pregnancy. The effect of different interventions on the glycemic profile (the continuous glucose monitoring (CGM) plus self-monitoring), lipid profile, gut hormone responses, inflammatory factors and metabolomics profiling (multi-omics data) will be monitored and compared. The pregnant outcome of the two groups will be also followed up and compared eventually. With all data reviewed and analyzed, this study will add evidence to the long-term health effect of pistachios on GDM women.

Official Title
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A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women

Conditions
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Gestational Diabetes Mellitus in Pregnancy

Intervention / Treatment
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* Other: pistachios consumption of 1.5 oz thrice per week


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese women at the age of 20-45 years, with Han ethnicity and singleton pregnancies Women who are at 20-30 weeks' singleton gestation and have the first onset of hyperglycemia which fulfills at least one of the following criteria: fasting glucose ≥5.1 mmol/L, 1 h glucose ≥10 mmol/L or 2 h glucose ≥8.5 mmol/L during the 2 h 75 g OGTT. Pregestational BMI greater than 24 kg/m2. Willing to comply with the research requirements Exclusion Criteria: Gastrointestinal malabsorption and chronic diseases that alter nutrient metabolism Allergy or intolerance to pistachios Pre-existing diabetes, insulin resistance, impaired fasting glucose or impaired glucose tolerance Pregnancy with more than one fetus Current or planned corticosteroid therapy Current or planned beta adrenergic therapy Chronic medical conditions such as HIV/AIDS, kidney disease, or congenital heart disease Hematologic or autoimmune disease such as sickle cell disease, other hemoglobinopathies, lupus, or antiphospholipid syndrome

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Interventional Model Description: All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Stand care control group (CG)<br>According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included participants, who all have the pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating nuts intake of less than 2.5 oz per week. | |
| Experimental: Intervention group (IG)<br>The participants in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. | Other: pistachios consumption of 1.5 oz thrice per week<br>* According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for all the included participants with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Blood glucose response at 2 months | Change from baseline of the blood glucose response (time-in-range (TIR) on CGM, Hgb A1c, area under the curve of postprandial blood glucose (CGM)) after the nutritional management over 2 months | up to 2 months | 
| The incidences of adverse maternofetal outcomes | The incidences of adverse maternofetal outcomes: emergency caesarean section (C-section), perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational age, and small-for-gestational age. | From date of intervention until the date of the delivery or termination of pregnancy, up to 4 months.. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline the lipid profile at 2 months | Change from baseline of the lipid profile (TG, TC, HDL-C, LDL-C) after the nutritional management over 2 months | up to 2 months | 
| Change from baseline the inflammatory factors at 2 months | Change from baseline of the inflammatory factors (IL-6, hsCRP) after the nutritional management over 2 months | up to 2 months |