Prediabetes
Conditions
Keywords
Dairy, Milk, Glucose, Postprandial, Hyperglycemia, Prediabetes, Blood glucose, Oxidative stress, Vascular health, Vascular function
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. 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
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.
Interventions
OTHERGlucose
Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.
OTHERGlucose with Whole Fat Milk
Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of whole fat milk within five minutes.
Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.
Sponsors
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Endothelial Function | Area under curve of FMD for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarker of Nitric Oxide Homeostasis (NOx) | Area under curve of nitrite/nitrate for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 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) |
| Glucose | Area under curve of glucose for three hours (0, 30, 60, 90, 120, 150, and 180 min) | 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) |
| Oxidative Stress Biomarker (Malondialdehyde; MDA) | Area under curve of MDA for three hours (0, 30, 60, 90, 120, 150, 180 min) | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either Glucose, Glucose + Whole Fat Milk, or Glucose + Non-fat Milk. All participants received all three treatments in a randomized order.
Each study day lasted approximately three hours and was separated from the other arms by four days for men and one month for women.
Glucose: Following baseline measurements, participants consumed a 75 g glucose solution within five minutes.
Glucose + Whole Fat Milk: Following baseline measurements, participants consumed 75 g glucose dissolved in two cups of whole fat milk within five minutes.
Glucose + Non-fat Milk: Following baseline measurements, participants consumed 75 g glucose dissolved in two cups of non-fat milk within five minutes. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 22 Participants | — |
| Age, Continuous | 31.7 years STANDARD_DEVIATION 1.8 | — |
| Body Mass Index | 31.6 kg/m^2 STANDARD_DEVIATION 1.2 | — |
| Carotid Artery Intima Media Thickness (cIMT) (left) | .59 mm STANDARD_DEVIATION 0.01 | — |
| Carotid Artery Intima Media Thickness (cIMT) (right) | .59 mm STANDARD_DEVIATION 0.01 | — |
| Diastolic Blood Pressure | 82.7 mmHg STANDARD_DEVIATION 1.7 | — |
| Fasting Glucose | 109.8 mg/dL STANDARD_DEVIATION 1.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 22 participants | — |
| Sex: Female, Male Female | 7 Participants | — |
| Sex: Female, Male Male | 15 Participants | — |
| Systolic Blood Pressure | 125.4 mmHg STANDARD_DEVIATION 2.3 | — |
| Total Cholesterol | 177.7 mg/dL STANDARD_DEVIATION 7.7 | — |
| Waist Circumference | 107.7 cm STANDARD_DEVIATION 3.3 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 4 | 0 / 5 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 5 |
Outcome results
Primary
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)
Time frame: Area under curve of FMD for three hours (0, 30, 60, 90, 120, 150, and 180 min)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Vascular Endothelial Function | -195.9 %*min | Standard Error 35.99 |
| Glucose With Whole Fat Milk | Vascular Endothelial Function | -6.181 %*min | Standard Error 47.2 |
| Glucose With Non-fat Milk | Vascular Endothelial Function | -5.629 %*min | Standard Error 36.92 |
Secondary
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)
Time frame: Area under curve of nitrite/nitrate for three hours (0, 30, 60, 90, 120, 150, and 180 min)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Biomarker of Nitric Oxide Homeostasis (NOx) | -2229 umol/L*min | Standard Error 343.3 |
| Glucose With Whole Fat Milk | Biomarker of Nitric Oxide Homeostasis (NOx) | -1240 umol/L*min | Standard Error 252.7 |
| Glucose With Non-fat Milk | Biomarker of Nitric Oxide Homeostasis (NOx) | -1221 umol/L*min | Standard Error 228.3 |
Secondary
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)
Time frame: Area under curve of glucose for three hours (0, 30, 60, 90, 120, 150, and 180 min)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Glucose | 6259 mg/dL*min | Standard Error 622.5 |
| Glucose With Whole Fat Milk | Glucose | 4481 mg/dL*min | Standard Error 652.4 |
| Glucose With Non-fat Milk | Glucose | 3408 mg/dL*min | Standard Error 574.7 |
Secondary
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)
Time frame: Area under curve of MDA for three hours (0, 30, 60, 90, 120, 150, 180 min)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Oxidative Stress Biomarker (Malondialdehyde; MDA) | 54.9 umol/L*min | Standard Error 7.653 |
| Glucose With Whole Fat Milk | Oxidative Stress Biomarker (Malondialdehyde; MDA) | 25.78 umol/L*min | Standard Error 9.505 |
| Glucose With Non-fat Milk | Oxidative Stress Biomarker (Malondialdehyde; MDA) | 31.3 umol/L*min | Standard Error 5.283 |