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

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. The health benefits of dairy on heart health are at least partly attributed to its ability to limit PPH and resulting PPH-mediated responses leading to vascular dysfunction. This provides rationale to further investigate dairy as a dietary strategy to reduce PPH and risk for CVD. The objective of this study is to define the extent to which dairy milk, and its whey and casein protein fractions, protect against postprandial 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 four, 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, 3. oral glucose challenge in combination with whey protein isolate, and 4. oral glucose challenge in combination with sodium caseinate. 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 Milk

Conditions
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Prediabetes

Intervention / Treatment
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* Other: Glucose
* Other: Glucose with Non-fat Milk
* Other: Glucose with Whey Protein Isolate
* Other: Glucose with Sodium Caseinate


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 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>|
| Experimental: Glucose with Whey Protein Isolate<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 Whey Protein Isolate<br>* Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.<br>|
| Experimental: Glucose with Sodium Caseinate<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 Sodium Caseinate<br>* Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water 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) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline) | Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nitrite/Nitrate (NOx) | NOx AUC for 0-180 minutes | Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline) | 
| Plasma Glucose | Plasma glucose concentration from 0-180 minutes | Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline) | 
| Malondialdehyde (MDA) | Plasma MDA measured as MDA AUC from 0-180 minutes | Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline) | 
| Arginine (ARG) | Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes | ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes | ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Symmetric Dimethylarginine/Arginine (SDMA/ARG) | Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes | SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes | Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Insulin | Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes | Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Cholecystokinin (CCK) | Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes | CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| 8-isoprostaglandin-F2a | Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes | 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| 8-isoprostaglandin-F2a/Arachidonic Acid | Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes | 8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 
| Arachidonic Acid | Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes | Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | 

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