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

Not Applicable

Completed

• Conditions: Prediabetes
• Interventions: Other: Glucose with Sodium Caseinate; Other: Glucose; Other: Glucose with Non-fat Milk; Other: Glucose with Whey Protein Isolate

• Registration Number: NCT02482675
• Lead Sponsor: Ohio State University

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-24
• Study First Submitted QC: 2015-06-24
• Study First Posted: 2015-06-26
• Primary Completion: 2016-07
• Study Completion: 2018-02
• Results First Submitted: 2018-03-28
• Results First Submitted QC: 2019-01-29
• Status Verified: 2019-05
• Results First Posted: 2019-05-03
• Last Update Submitted: 2019-05-04
• Last Update Posted: 2019-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

1. hemoglobin A1c 5.7-6.4%
2. non-dietary supplement user
3. no medications affecting vasodilation, inflammation, or energy metabolism
4. no CVD
5. nonsmokers
6. individuals having blood pressure <140/90 mmHg and total cholesterol <240 mg/dL

Exclusion Criteria

1. unstable weight (±2 kg)
2. vegetarian or dairy allergy
3. alcohol intake >3 drinks/day or >10 drinks/week
4. ≥7 hours/week of aerobic activity

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glucose with Sodium Caseinate	Glucose with Sodium Caseinate	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.
Glucose	Glucose	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.
Glucose with Non-fat Milk	Glucose with Non-fat Milk	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.
Glucose with Whey Protein Isolate	Glucose with Whey Protein Isolate	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.

Primary Outcome Measures

Name	Time	Method
Vascular Endothelial Function	Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)	Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Ohio State University; 🇺🇸 Columbus, Ohio, United States