Clinical trial NCT02482675: Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk
Official title: Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetes
Keywords: Dairy
Milk
Glucose
Postprandial
Hyperglycemia
Prediabetes
Blood glucose
Oxidative stress
Vascular health
Vascular function
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2015-06-26
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Vascular Endothelial Function
timeFrame: Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)
Secondary outcomes:
measure: Nitrite/Nitrate (NOx)
timeFrame: Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)
measure: Plasma Glucose
timeFrame: Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)
measure: Malondialdehyde (MDA)
timeFrame: Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)
measure: Arginine (ARG)
timeFrame: ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Asymmetric Dimethylarginine/Arginine (ADMA/ARG)
timeFrame: ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Symmetric Dimethylarginine/Arginine (SDMA/ARG)
timeFrame: SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)
timeFrame: Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Insulin
timeFrame: Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Cholecystokinin (CCK)
timeFrame: CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: 8-isoprostaglandin-F2a
timeFrame: 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: 8-isoprostaglandin-F2a/Arachidonic Acid
timeFrame: 8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
measure: Arachidonic Acid
timeFrame: Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Richard S Bruno, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27;131(4):e29-322. doi: 10.1161/CIR.0000000000000152. Epub 2014 Dec 17. No abstract available.
citation: DECODE Study Group, the European Diabetes Epidemiology Group.. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001 Feb 12;161(3):397-405. doi: 10.1001/archinte.161.3.397.
citation: Ballard KD, Bruno RS. Protective role of dairy and its constituents on vascular function independent of blood pressure-lowering activities. Nutr Rev. 2015 Jan;73(1):36-50. doi: 10.1093/nutrit/nuu013.
citation: Ballard KD, Mah E, Guo Y, Pei R, Volek JS, Bruno RS. Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments in vascular endothelial function in obese individuals with metabolic syndrome. J Nutr. 2013 Oct;143(10):1602-10. doi: 10.3945/jn.113.179465. Epub 2013 Aug 21.
citation: McDonald JD, Mah E, Chitchumroonchokchai C, Dey P, Labyk AN, Villamena FA, Volek JS, Bruno RS. Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem. 2019 Jan;63:165-176. doi: 10.1016/j.jnutbio.2018.09.018. Epub 2018 Sep 25.