Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Fat

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) is the leading cause of death in the United States. Short-term increases in blood sugar, or postprandial hyperglycemia (PPH), affect blood vessel function and increase the risk of CVD. Greater intakes of dairy foods have been associated with a lower risk of CVD, but whether these effects occur directly or indirectly by displacing foods in the diet that might increase CVD risk is unclear. Further controversial is the extent to which dietary fat derived from dairy foods regulate the risk of CVD. The health benefits of dairy on CVD risk are at least partly attributed to its ability to limit PPH and resulting PPH-mediated responses leading to vascular dysfunction. This provides rationale to investigate full-fat containing dairy as a dietary strategy to reduce PPH and risk for heart disease. The objective of this project is to define the extent to which full-fat dairy milk compared to non-fat dairy milk protects against PPH-induced vascular dysfunction by reducing oxidative stress responses that limit nitric oxide bioavailability to the vascular endothelium in adults with prediabetes.

Detailed Description
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This study consists of three, 3-hour postprandial trials in response to consuming the following dietary treatments: 1. oral glucose challenge, 2. oral glucose challenge in combination with non-fat milk, and 3. oral glucose challenge in combination with whole milk. For three days preceding each trial, participants will be provided all meals to standardize physiologic responses to test meals. On each trial day, vascular function will be assessed and blood samples collected prior to and at 30 minute intervals for 3 hours following test meal ingestion.

Official Title
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Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Fat

Conditions
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Prediabetes

Intervention / Treatment
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* Other: Glucose
* Other: Glucose with Whole Fat Milk
* Other: Glucose with Non-fat Milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hemoglobin A1c 5.7-6.4% non-dietary supplement user no medications affecting vasodilation, inflammation, or energy metabolism no CVD nonsmokers individuals having blood pressure <140/90 mmHg and total cholesterol <240 mg/dL Exclusion Criteria: unstable weight (±2 kg) vegetarian or dairy allergy alcohol intake >3 drinks/day or >10 drinks/week ≥ 7 hours/week of aerobic activity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucose<br>This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women. | Other: Glucose<br>* Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.<br>|
| Experimental: Glucose with Whole Fat Milk<br>This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women. | Other: Glucose with Whole Fat Milk<br>* Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of whole fat milk within five minutes.<br>|
| Experimental: Glucose with Non-fat Milk<br>This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women. | Other: Glucose with Non-fat Milk<br>* Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Endothelial Function | Flow mediated dilation (FMD) evaluated on the basis as change from baseline to calculate FMD area under the curve from 0-180 min, i.e. i.e. Area Under the Curve (AUC) of change from baseline in FMD from 0 min to 180 min (i.e., AUC (FMD 0 min- 0 min, FMD 30 min-0 min, FMD 60 min-0 min, etc) | Area under curve of FMD for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker of Nitric Oxide Homeostasis (NOx) | Biomarker of nitric oxide homeostasis is based on the assessment of total nitrite and nitrate concentrations. Changes relative to baseline were used to calculate area under the curve of total nitric oxide metabolites from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in nitric oxide homeostasis from 0 min to 180 min (i.e., AUC (NOx 0 min- 0 min, NOx 30 min-0 min, NOx 60 min-0 min, etc) | Area under curve of nitrite/nitrate for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 
| Glucose | Glucose concentrations evaluated on the basis as change from baseline to calculate glucose area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in glucose from 0 min to 180 min (i.e., AUC (glucose 0 min- 0 min, glucose 30 min-0 min, glucose 60 min-0 min, etc) | Area under curve of glucose for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 
| Oxidative Stress Biomarker (Malondialdehyde; MDA) | MDA concentrations evaluated on the basis as change from baseline to calculate MDAarea under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in MDA from 0 min to 180 min (i.e., AUC (MDA 0 min- 0 min, MDA 30 min-0 min, MDA 60 min-0 min, etc) | Area under curve of MDA for three hours (0, 30, 60, 90, 120, 150, 180 min) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood glucose, Dairy, Milk, Glucose, Postprandial, Hyperglycemia, Prediabetes, Oxidative stress, Vascular health, Vascular function